PORTAL TO "JUNK" DNA
"...a certain amount of hubris* was required for anyone to call any part of the genome 'junk'"
Francis Collins (2006)
* hubris: (Greek) "Overbearing pride or presumption; arrogance"
Fractal development by Jules Ruis
MONITORING THE POSTMODERN ERA OF GENOMICS ("BEYOND GENES"):
(17 Jan) BioDiscovery Joins Microsoft BioIT Alliance [How about GOOGLE?]
(12 Jan) Micro[RNA] Molecules Can Identify Pancreatic Cancer
(11 Jan) Asuragen Licenses Yale miRNA Inventions with Potential in Lung Cancer
(10 Jan) NMC Group to set up facility at DuBiotech [put Dubai on the map of PostGenetics]
(06 Jan) Renegade RNA: Clues To Cancer And Normal Growth
(05 Jan) Improved Quarter for Biotech on Capital Markets ... and Financings and Partnering Deals Remain Red Hot
(04 Jan) Sirna's Shaky Shareholder Settlement Sheds Light on Merck Acquisition
(03 Jan) How Do MicroRNAs Regulate Gene Expression?
(02 Jan) The Evolution of Junk DNA from mostly Non-functional to Mostly Functional
(30 Dec) Areas to Watch in 2007 [for "Top 10 of Science", Whole-genome association studies]
(29 Dec) Sirna shareholders approve $1.1 billion sale of company to Merck
(28 Dec) Minute manipulations [piRNA in "Top 10" of Science in 2006]
(22 Dec) Ancient Noncoding Elements Conserved in the Human Genome
(21 Dec) And in the beginning was RNA
(15 Dec) Repetitive Elements Round Up
(15 Dec) Korea to Invest $14 Billion in Biotech
(13 Dec) A Cryptologist Takes a Crack at Deciphering DNA’s Deep Secrets
(12 Dec) Genome scientist knows himself inside out
(09 Dec) What will be the biggest benefit from mapping human genome?
(08 Dec) Peering Into The Shadow World Of RNA
(28 Nov) Venter hopes to develop drugs from ocean microbes [Scripps, San Diego]
(27 Nov) New Technology Used To Construct First Map Of Structural Variation In Human Genome
(26 Nov) Junk DNA in Y-chromosome control functions
(23 Nov) New diversity discovered in human genome [welcome again to PostGenetics...]
(23 Nov) The Discovery of DNA variability
(22 Nov) DNA methylation profiling of human chromosomes 6, 20 and 22
(21 Nov) NLM Awards $75M for Biomedical Informatics Training Programs
(19 Nov) Taking 'chips' to the next level of [non]-gene hunting
(17 Nov) God vs. Science [article on Junk or article permitting junk?]
(16 Nov) RNA polymerase III transcribes human microRNAs [FractoGem-s are miR-acle sites?]
(08 Nov) TCAG - The Institute for Genomic Research, Venter Institute, Venter Science Foundation Consolidate
(05 Nov) Study to genotype six common ["junk DNA"] diseases
(02 Nov) MIT's anti-microbial 'grammar' posits new language of healing
(31 Oct) Human Epigenome Project generates DNA methylation profiles of three chromosomes
(30 Oct) MicroRNA evolution put to the test
(27 Oct) Genetic Repair Mechanism Clears The Way For Sealing DNA Breaks
(25 Oct) NSF awards UGA $4.1 million grant to study so-called 'jumping genes' in maize
(12 Oct) International PostGenetics Society European Inaugural
(05 Oct) Broad Institute to study causes of cancer as part of $100 million award
(04 Oct) Time Aping over Human-Chimp Genetic Similarities
(03 Oct) Nobel in Medicine 2006 - for the discovery of RNA interference - gene silencing by double-stranded RNA
(28 Sep) Cancer Research UK: 'Junk’ RNA could help halt development of cancer
(26 Sep) Implications of fractal organization of DNA on disease risk genomic mapping and immune function analysis
(23 Sep) RNA-what's next? [Tip of a very big iceberg]
(22 Sep) IBM & Genome Institute of Singapore Collaboration May Lead to Better Understanding of Cell Process Regulation
(21 Sep) Genome encodes a hidden RNA regulatory system that controls differentiation and development
(20 Sep) After the Genome [in PostGenetics, "sand dunes" of "junk DNA" are beneath waterline...FractoGem peaks emerging...]
(12 Sep) PostGenetics "housekeeping" announcements
(11 Sep) Sheep need retroviruses for reproduction
(09 Sep) The Language of God: A Scientist Presents Evidence for Belief
(01 Sep) Human Evolution: The More the Merrier [Journalists, too, may wish to think outside the box]
(01 Sep) What’s Shaped Like a Pear and Has Two Genomes? Check The Pond. [For "junk" DNA - Check the source]
(31 Aug) Variability in SNCA associated with increased risk of Parkinson's. [A FractoGem of SNCA]
(22 Aug) NHGRI Grants $54 M for "In Toto" Genomic Analysis
(16 Aug) Region of DNA strongly associated with Alzheimer's disease [clue of Alz may lie in the "junk"]
(16 Aug) Sequencing the Seven Seas - "Google for Genomics"
(16 Aug) Research finds 'unique human DNA' [clue to being human may lie in the "junk"]
(15 Aug) RNA translation misfolding proteins
(08 Aug) Non-coding RNA in the nervous system
(05 Aug) Sinking the Iceberg: GOOGLE Genomics?
(31 Jul) Rosetta Genomics signs agreement with Max Planck Society [short sequences are a goldmine]
(28 Jul) Beyond Genetics - Nucleosomes; sequence repeats and DNA binding with proteins are established facts
(19 Jul) Venture capitalists awash with cash -- may soon beg you to take some
(19 Jul) The Quest for the $1,000 Human Genome [Venter or Watson? Private business or Government? competition is nice]
(14 Jul) Craig Venter plans to publish the entire code of his own DNA
(13 Jul) The Biggest DNA Ever Made
(12 Jul) Photoshop For DNA
(09 Jul) Down syndrome traced to one gene [FractoGem emerges!]
(04 Jul) How did all this junk get here anyway?
(27 Jun) RNAi Gene silencing causes marked behavior changes, may help map brain circuitry
(27 Jun) Epigenomics and Sanger Institute Release First Results from Human Epigenome Project [Methylated DNA sites and PostGene Discovery]
(26 Jun) DNA or RNA? Versatile Player Takes a Leading Role in Molecular Research
(17 Jun) New class of small RNAs found
(15 Jun) Live From Nanobusiness 2006: Synthetic Genomics and the "Triple Helix"
(14 Jun) Rosetta Genomics buys rights to Rockefeller U MicroRNA [Cornering the junk-market on the cheap]
(13 Jun) Nutrigenomics may have go-go potential [It is not so much the Junk Food - it is rather the 'Junk' DNA]
(12 Jun) FractoGem of Alzheimer's
(07 Jun) * NEWSFLASH * FractoGem-s Found in DNA of 3 Human Non-coding DNA Diseases
(28 Apr) Moore Foundation-funded link of UCSD and VENTER Institute [Big IT bites into Genomics, next round]
(24 Apr) IBM seeks treasure in 'junk DNA' [IBM found repetitions - GOOGLE might search by the algorithm of patterns & silencing]
(21 Apr) Of cod and code [It is fishy to say "To code or not to code - that is the (IT) question"]
(20 Apr) Counting the dead [Lesson of Chernobyl 20 years ago: 'Junk DNA' Minisatellites mutated]
(18 Apr) Genome scan pinpoints common obesity factor [Junk Food or Junk DNA?]
(10 Apr) PERLEGEN files for IPO; Seeks to raise up to $115 M [Junk DNA Intellectual Property question]
(10 Apr) Victoria, Australia and VENTER INSTITUTE join for whole genome sequencing. [Juan Enriquez was right]
(06 Apr) GOOGLE accused of biopiracy [New type of DNA dabase needed: safedna.com]
(05 Apr) HHMI Investigators J. Steitz and R. Evans Awarded [Gairdner prize for 'JunkDNA']
(02 Apr) Scientists in the making bag laurels [from DuPONT Student prize towards Nobel in 'JunkDNA']
(02 Apr) Matt Ridely: Selfish DNA [of Richard Dawkins] and the junk in the genome
(02 Apr) Antifreeze fish make sense out of junk DNA
(27 Mar) AFFYMETRIX new ChIP-on-Chip array; Tools for DNA-Protein interactions [Bingo; Methylation Prediction of FractoGene]
(26 Mar) Regulatory DNAs may be missed [without new tools for PostGene Discovery]
(24 Mar) Junk DNA may not be so junky after all [Zebrafish is a great PostGene discovery platform, but where are the tools?]
(22 Mar) Loveable rogue, or selfish killer? [The Selfish PostGenes are to be found by "Methylation Prediction"]
(20 Mar) Justices reach put to consider patent case [The question is not if IP has value - the question is the limit of value]
(14 Mar) GTG reports breakthrough in the genetic basis of drug addiction [the new definition of "Junkie"]
(12 Mar) Differences between chimps and man lie in fraction of code ["Probably the biggest aboutface in the history"]
(10 Mar) Most human-chimp differences due to gene regulation - not genes [Platforms of liver and perhaps the brain?]
(09 Mar) Time for a human interactome project? [www, re-visited]
(06 Mar) J. Craig Venter: He might change the world [which World?]
(05 Mar) Advances in aging research [The limit of information for life]
(28 Feb) Non-coding RNA vital vor gene activation and protein expression [PostGene sets found for differentiation]
(27 Feb) ISIS - ROSETTA Collaboration for micro-RNA therapies for liver cancer [Next PostGene Disease & Next Business Model]
(25 Feb) [continued...] A question for 150,000 diseases - Parkinson's is a good example
(24 Feb) Michael J. Fox: Welcoming remarks at inaugural World Parkinson Congress [to be continued...]
(22 Feb) Unlocking the secrets of longevity genes [How big is your 'season ticket' to life?]
(19 Feb) Kleiner Perkins Caufield & Byers Forms $200 Million Pandemic and Bio Defense Fund [PostGenentech or Manhattan Project?]
(19 Feb) Kleiner Perkins Caufield & Byers Forms $600 M Fund, $100 M Greentech Initiative [KPCB throws in close to a Billion in 3 funds]
(14 Feb) COMPUGEN Announces In-Silico Protein Discovery from ''Junk DNA'' [PostGene Discovery at work]
(08 Feb) NIH 2 Initiatives for Genetic Causes of Disease; PFIZER & AFFY [The PostGenetics Avalanche has started]
(07 Feb) Scientists Sort Through 'Junk' to Unravel a Genetic Mystery [New York Times - PostGenetic Medicine]
(02 Feb) PostGenetic Information Technology & Intellectual Property [Articles on Venter/Genentech/Microsoft/Google/UCSD/Affymetrix, GTG]
(01 Feb) PostGenetic Medicine [Neurological and cardiovascular diseases and CArG box]
(31 Jan) Missing steps of jumping-gene replication discovered
(26 Jan) Olympics time? Try Little Italy [NBC TV: According to the research, you are half a banana]
(26 Jan) Changing of the guard as UQ Institute reaches maturity [Mattick resigns in order to challenge the dogma of "Junk" DNA]
(24 Jan) New Affymetrix Tiling Arrays DeliverView of Entire Genomes; Experiments Using GeneChip Microarrays Challenge ''Junk'' DNA
(24 Jan) Are chimps our second cousins? [A science issue is dangerously neglected]
(19 Jan) Tiny RNA molecules fine-tune the brain's synapses - A new mechanism for regulating brain function
(18 Jan) Science Matters: The ups and downs of evolution [PostGenetics; the Science and Medicine of non-coding DNA]
(18 Jan) GOOGLE and Venter Mum on Collaboration Reports
(13 Jan) Taylor & Francis publishes Experimental Evidence Supporting Algorithmic PostGene Theory [FractoGene].
(12 Jan) "PostGenetics" (Journal of IPGS) is planned to be launched with European Inaugural of IPGS
(12 Jan) CETT Program in U.S. for rare genetic diseases [Proposal for "Congressional Lobby Activity on PostGenetic Medicine by IPGS"]
(08 Jan) The Big One [Steve Jurvetson of DFJ funds $ 30 M to Craig Venter's Synthetic Genomics - 30 December, 2005]
(07 Jan) "Ultraconserved elements [UE]" - "Disease Gene Conserved Sequence Tags" [DG-CST]" - "Transposon-free regions [TFR]" - "FractoGene BrowserBook" [FractoGene] - "PostGene Diseases" [PGD]
(07 Jan) Evo-devo next big thing, not intelligent design
(03 Jan) Non-obviousness of "junk" DNA theory - and inventory as 2006 starts
(03 Jan) Origin of a big idea [with small evidence...]
(31 Dec) Biotechnology bucks the market trend [the "Big Picture" of 2005]
(30 Dec) 2005 ends with a flurry of deals, positioning for the emerging disruptive PostGenetics business
(29 Dec) Perlegen, Pfizer Pen Four-Year PGx Partnership; Deal Covers IP Rights, Research Payments ["Bidding war" in the offing?]
(28 Dec) Pfizer Buys $ 50 M Stake in Perlegen; 12-Percent Ownership Could Grow If IPO Launched
(27 Dec) Banned in biology [Welcoming Bill Gates]
(24 Dec) Role of MicroRNA Identified In Thyroid Cancer ["PostGenes, PostGene Diseases, PostGenetic Medicine"]
(23 Dec) Cedars-Sinai researchers demonstrate a new way to switch therapeutic genes 'on' and 'off [PostGenetic Medicine is just a turn-on?]
(25 Dec) Breakthrough of the Year [of 1859]: Evolution in Action [What is news? Dog Bites Man, or "Man Bites Dog"?]
(23 Dec) Evolution in Action Highlighted in Science’s "Breakthrough of the Year" [of 1859]
(19 Dec) Civilisation has left its mark on our genes [correction, on human Genome]
(17 Dec) Probing Connection Between Regulatory DNA And Disease [ NEW TOOLS ARE NEEDED]
(19 Dec) GTG/GENE stock holds steady - what's next?
(16 Dec) Plan matures for partner to genome quest. Forget mutations: geneticists are hunting for subtler changes to DNA [Methylation].
(16 Dec) Genetic wins little fight over DNA work ["Junk" DNA is cheap or it is still an incredible bargain?]
(15 Dec) GTG Provides Further Details of the Settlement with Applera
(14 Dec) New Effort Aims to Unlock Secrets of Cancer Genes ["Don't blame me, I joined 'PostGenetics', focusing on 'Junk DNA' diseases"]
(13 Dec) [Hold it! - there is more to 'Junk DNA Industry'. Further announcement regarding GTG / APPLERA settlement]
(12 Dec) [Now it is official - The "Junk DNA Intellectual Property value proposition is forever validated"]
(10 Dec) [Half a Billion Dollars from Bill Gates for] Anti-Malaria Donation [Maybe software would help more directly?]
(09 Dec) Barking up new trees in search for cures [ALERT! The secret of your illness may well be in the 'junk' DNA"]
(09 Dec) Veil of secrecy "costs" GTG/GENE a 10% drop in stock price on a single day
(08 Dec) Man's best friend shares most genes with humans: [Triple whammy - time sobering up!]
(06 Dec) 'Junk DNA' Stock of GTG [NYSE symbol "GENE"] jumps 8.47% on a single day anticipating settlement tomorrow
(05 Dec) Further Update regarding Applera Dispute - [Court allows one more workday to settle with "GENE"]
(01 Dec) Startup Haplomics to Muscle In on Gene-Testing Market
(01 Dec) MicroRNA may have fail-safe role in limb development
(01 Dec) SETI and Intelligent Design
(01 Dec) Treasures in the Trash [Forbes Magazine]
(28 Nov) The elusive fountain of youth
(27 Nov) Rosetta Genomics' Isaac Bentwich: "Dark DNA" may be even more important than active genes in causing disease
(25 Nov) The earliest animals had human-like genes
(24 Nov) GTG and APPLERA ask Court time till 5th of December to finalize Junk DNA patent settlement
(19 Nov) Oops - the price of junkDNA just took off ... "junk DNA" is the word ...
(11 Nov) Further update regarding 'Junk DNA on Wall Street' (GTG settles with Applera) - an analysis
(09 Nov) JunkDNA made it to Wall Street - GTG earmarked to escalate to a $ 2 Billion business alone
(07 Nov) "Stipulated Revised Case Schedule and Order" on GTG website GTG, Applera Look to Be Nearing Settlement
(02 Nov) The American Heart Association donated about $1.23 M to fund University projects
(27 Oct) NHGRI's Collins Says US Must Launch Its Own Biobanking Project
(27 Oct) The Role of Junk DNA in Social Behavior
(20 Oct) Study: Junk DNA is critically important
(17 Oct) METHYLATION HYPOTHESIS OF FRACTOGENE;Predictive Scientific Theories on the Function of 'junk DNA'
(17 Oct) "Taxpayer Alert": Large-scale Sequencing Research Network Sets Its Sights On Disease Targets
(12 Oct) Smoking chimps show similarities to humans
(05 Oct) The greatest discovery of all time ("ET joins ED")
(04 Oct) Harmful Mutations Selectively Eliminated
(28 Sep) Experimental support of the FIRST PREDICTION OF "FRACTOGENE accepted for publication (in Press)
(26 Sep) New Analyses Bolster Central Tenets of Evolution Theory
"You only believe theories when they make predictions confirmed by scientific evidence"
(26 Sep) NIH Launches Program to Study Genetics and Genomics of Xenopus
(26 Sep) Search for genetic origins of disease
(23 Sep) There is more to non-coding DNA than meets the eye
(13 Sep) Rosetta Genomics raises $ 6 M in fourth round
(05 Sep) Importance of 'junk' DNA found
(05 Sep) Junk RNA Begins To Yield Its Secrets
(31 Aug) Scientists find chimps, people are 96 percent identical; San Jose Mercury News
(31 Aug) 'Life code' of chimps laid bare: BBC
(31 Aug) What does the fact that we share 95 percent of our genes with the chimpanzee mean? Sci. Am.
(31 Aug) Sisters under the skin; The Economist
(31 Aug) Study_compares_human_and_chimpanzee_DNA; Nature News
(31 Aug) Reading the chimp book of life; BBC
(31 Aug) Scientists find missing links in chimp genome; Guardian
(19 Aug) Genetic Efficiency and the Carbon Cycle; New Scientist
(30 Jul) Newsweek on JunkDNA
(14 Jul) Genomics study highlights the importance of junk DNA in higher eukaryotes
(04 Jul) The most successful business model of California Gold Rush - *toolmaking*
(29 Jun) Venter launches Synthic Genomics; Bacterium to generate hydrogen
(23 Jun) Junk DNA on National Television - "Extra DNA Makes Voles Faithful"
(21 Jun) Rosetta Genomics identifies hundreds of novel human microRNAs
(20 Jun) Founders of "The Human Genome Project" are ready to "re-thinking it all"... The Uncertain Future for Central Dogma
(16 Jun) The Economist: Helpful junk
(16 Jun) Rodent Social Behavior Encoded in Junk DNA
(31 May) Affy to Buy ParAllele for $ 120 M in Stock; Deal Expected to Close in Q3
(31 May) Agilent, Rosetta Biosoftware to Integrate Gene Expression Analysis Software
(27 May) Biochemistry Graduate Student Receives UCR Award for Outstanding Research
(30 May) Israel’s Rosetta Genomics - Cracking the RNA Code
(25 May) Agilent to Acquire Informatics Company Scientific Software for Undisclosed Amount
(22 May) Israel's Rosetta Genomics - cracking the RNA code
(18 May) Debating the Merits of Intelligent Design
(18 May) Gene researchers find variations by ancestry
(27 Jan) Scientists Find Genome Structure Responsible for Gene Activation
(20 Jan) Highly Conserved Non-Coding Sequences [Submitted by IPGS Founder M. Achiriloaie]
(19 Jan) Scientists Decipher Genome Of Bacterium That Helps Clean Up Major Groundwater Pollutants
(14 Jan) Study finds more than one-third of human genome regulated by RNA [Affymetrix]
(14 Jan) Fujitsu BioSciences Licencses BioMedCAChe to GPC Biotech; New Version Due This Quarter
(07 Jan) Pharmacogenomics to Benefit from Steven Burrill's New $ 300 M - $ 500 M Life Sciences Venture Capital Fund
(05 Jan) Agilent Acquires Computational Biology in Bid to Expand Microarray Platform
(07 Jan) Pufferfish genome clue to human and animal development
(05_Jan) Affy Says Sales Surpassed $100 M in Q4 '04, a 17-Percent Increase
(05 Jan) Shares in Affymetrix Jump 6.95 % on News of Record Sales Growth
(31 Dec) "Junk DNA":Top 10 Science Discoveries - 2004 Science Magazine
(28 Dec) Top 10 Science stories, 2004 ["Junk DNA" "shapes the coding for protein production"]
(27 Dec) Sun Gives Grid Cluster to India Institute of Bioinformatics
(27 Dec) Researchers Shed Light On Intron Evolution
(13 Dec) In our Post Gene Era a clear emphasis is put on Information Technology [see Pellionisz-Simons]
(13 Dec) Allen Institute Debuts 'Google for Gene Activity' [$ 100 M]
(10 Dec) DVD: "Junk DNA is not JUNK" [Creationism]
(05 Dec) The Sunday Times - Britain's 10 M Pounds - Chicken genes help crack the dinosaur code
(05 Dec) Tiny microbes make us who we are, scientist says
(04 Dec) Complete chicken genome map revealed [comments by Malcolm J. Simons, IPGS Honorary Chairman]
(26 Nov) German Research Foundation to Fund Collaborative Genomics Project [$ 490 M]
(26 Nov) The Government Funding Dam broke; NSF, NIH programs
(20 Nov) Human gene number slashed [to 20,000]
(15 Nov) Agilent and ExonHit Partner to Develop Microarray for Splice Variants
(11 Nov) Research effort seeks A's to gene expression Q's [Perlegen and J&J]
(03 Nov) US genetics win a shot in the arm [GTG vs. Applera]
(22 Oct) Affymetrix Launches Encode Array to Uncover Hidden Function of Human Genome
(20 Oct) Golden DNA goose [Rosetta Genomics, Israel]
(20 Oct) Mice do fine without 'junk DNA' [Questioned by Haussler, Pellionisz, Simons]
(20 Oct) Fish Tales Solve Genetic Puzzles [Fugu]
(11 Oct) 'Junk' DNA may be very valuable to embryos
(03 Oct) Doctor's race against time [Malcolm J. Simons' GTG and Haplomics patents]
(01 Oct) The Hidden Genetic Program of Complex Organisms [Mattick, Sci. Am.]
(29 Sep) New research shows plants can shuffle and paste gene pieces to generate genetic diversity
(15 Sep) Human chromosome 5 sequence analysis released.Disease genes,regulator elements populate terrai
(02 Sep) Glowing Green Proves Darwin Theory
(29 Jun) Newborn Introns [contributed by IPGS Honorary Chairman Malcolm Simons]
(22 Jun) The Scientist : Lab mouse genome isn't simple
(02 Jun) Junk DNA regulates neighboring gene [contributed by Steve Jurvetson, DFJ]
========== NEWS IN DETAIL ==========
[January 17, 2007]
NEW YORK (GenomeWeb News) BioDiscovery has joined the BioIT Alliance, the company reported yesterday.
BioDiscovery President Soheil Shams said involvement in the Alliance will “strengthen our competence in providing cross-platform, integrated software solutions.”
The BioIT Alliance is a diverse group of IT and biotech companies working with Microsoft to advance biomedical information technology through partnerships and shared knowledge on a range of issues.
Other BioIT Alliance members include Applied Biosystems, Affymetrix, Agilent, and Accelrys.
[The "Big One" earthquake when the "IT tectonic plate" will pile up on the "Genome tectonic plate" was predicted by A.Pellionisz and M.Simons by June 2004. Formation of BioIT Alliance was also duly reported in this column. With MicroSoft having pitted a tent, there is one obvious question: "What's in Genomics to GOOGLE"? To the extent of public information this column is on record with reporting what can be revealed - comment on the 17th of January, 2007 by A. J. Pellionisz]
A pattern of micro molecules can distinguish pancreatic cancer from normal and benign pancreatic tissue, new research suggests.
The study examined human pancreatic tumor tissue and compared it to nearby normal tissue and control tissue for levels of microRNA (miRNA). It identified about 100 different miRNAs that are present usually at very high levels in the tumor tissue compared with their levels in normal pancreatic tissue.
The findings suggest that miRNAs form a signature, or expression pattern, that may offer new clues about how pancreatic cancer develops, and they could lead to new molecular markers that might improve doctors' ability to diagnose and treat the disease.
Pancreatic cancer is expected to strike 33,700 Americans and to kill 32,300 others this year, making it the fourth leading cause of cancer death. The high mortality rate - the number of new cases nearly equals the number of deaths - exists because the disease is difficult to diagnosis early and treatment advances have been few.
The study, led by cancer researchers at the Ohio State University Comprehensive Cancer Center, was published online in the International Journal of Cancer.
"Our findings show that a number of miRNAs are present at very different levels in pancreatic cancer compared with benign tissue from the same patient or with normal pancreatic tissue," says principal investigator Thomas D. Schmittgen, associate professor of pharmacy and a researcher with the Ohio State's Comprehensive Cancer Center.
"Most are present at much higher levels, which suggests that developing drugs to inhibit them might offer a new way to treat pancreatic cancer. It also means that a test based on miRNA levels might help diagnose pancreatic cancer."
miRNAs are extremely short molecules that were discovered about a dozen years ago and found to be important for controlling how proteins are made. Scientists have now identified more than 470 different miRNAs in humans. More recent research has shown that miRNAs also play an important role in cancer.
"A big problem we face with pancreatic cancer is an inability to detect tumors early," says Russell Postier, chairman of surgery at the University of Oklahoma Health Science Center and a co-author of the study.
"The exciting findings in our work indicate that there is a microRNA gene-expression pattern that is unique to pancreatic tumors, and this might be useful in diagnosing pancreatic cancer in the future."
For this study, the researchers used a technique developed by Schmittgen and a group of colleagues in 2004 to measure miRNA in small tissue samples. The method is based on a technology called real-time PCR profiling, which is highly sensitive and requires very small amounts of tissue, Schmittgen says.
The researchers used the method to compare the levels of 225 miRNAs in samples of pancreatic tumors from patients with adjacent normal tissue, normal pancreatic tissue and nine pancreatic cancer cell lines.
Computer analysis of the data identified a pattern of miRNAs that were present at increased or decreased levels in pancreatic tumor tissue compared with normal tissue. The analysis correctly identified 28 out of 28 pancreatic tumors, 11 of 15 adjacent benign tissues and six of six normal tissues.
Levels of some miRNAs were increased by more than 30- and 50-fold, with a few showing decreased levels of eight- to 15-fold.
Schmittgen and his colleagues are now working to learn which of the miRNAs they identified are most important for pancreatic cancer development, and if some are found only in pancreatic cancer and not in other types of cancer.
[Not only microRNA-s, but computer analysis of pattern of miRNA - comment on the 12th of January, 2007 by A. J. Pellionisz]
Jan 10 2007, 12:30 PM EST
GEN News Highlights
Asuragen gained exclusive access to Yale University’s inventions developed by Frank Slack, Ph.D., for the regulation of oncogenes by microRNA's.
"By taking this license, Asuragen continues to strengthen its position as the leader in the application of miRNAs for diagnostics and therapeutics", states Matt Winkler, CEO/CSO of Asuragen. "We believe that recent advances in the application of siRNAs and the acquisition of Sirna Therapeutics by Merck & Co., confirms that RNA chemistries are overcoming previous clinical hurdles and sets the stage for potential miRNA therapeutic applications."
Dr. Slack discovered that among the genes regulated by the microRNA let-7 in the nematode C. elegans, there are several genes related to cancer, including the homolog of the human oncogene ras. A collaboration between scientists in the Slack laboratory and at Asuragen revealed that human let-7 regulates the expression of ras and that mis-regulation of let-7 in human lung cells likely contributes to the development of lung cancer via altered expression of ras.
"Our hope is that we can use let-7 as a potential diagnostic tool to diagnose lung cancers in patients," Dr. Slack explains. "And secondly, potentially use let-7 as a way to knock out activated ras in those lung cancers."
In addition to this license agreement, Asuragen will also fund Dr. Slack’s miRNA research.
[MicroRNA-s are in the Pharma biz to stay. Pharma will "mop up" the outstanding Intellectual Property. Though financial details (of course) are not disclosed, one assumes that Dr. Slack, for having his research funded by Pharma, had to sign assignment of his IP to Asuragen - comment on the 11th of January, 2007 by A. J. Pellionisz]
NMC Group to set up facility at DuBiotech [put Dubai on the map of PostGenetics]
By Saifur Rahman, Business News Editor
Dubai: Abu Dhabi-based New Medical Centre (NMC) Group will set up a multi-billion dollar bio-technology plant at the Dubai Biotechnology and Research Park (DuBio-tech), the region's biotech hub currently being developed.
"This will be a multi-billion dollar project and the first of its kind in the region," Dr BR Shetty, vice-chairman of NMC Group, told Gulf News yesterday. "We have sought land at DuBiotech for the project, which is still in early stage of development. Once we are given the land, we will be able to start working." Announced in February 2005, DuBiotech is a science and business park dedicated to the biotech industry, set within a free zone infrastructure. DuBiotech has two main areas of interest.
US-based project managers Parsons and CUH2A, the world's largest professional services firm dedicated to planning and design of science and technology facilities, are currently carrying out the master plan of DuBiotech. Dr Shetty's pharmaceutical plant, Neopharma recently signed an agreement with leading biotechnology major, Biocon, to produce biomedicine in Abu Dhabi.
Through this joint venture, the two companies will leverage on each other's strengths to manufacture and market biopharmaceutical products for the GCC region. The joint venture will bring out life saving drugs in the field of oncology, diabetes, auto-immune disorders and cardiology. The product mix will also include anti-obesity drugs and new generation immunosuppressant drugs.
"The agreement will allow us to produce Biocon's patented bio-medicine in the UAE - the first such attempt," he said.
Biocon is India's leading biotechnology enterprise. Over the past 28 years, they have evolved from an enzyme manufacturing company to a fully integrated biopharmaceutical enterprise. They apply proprietary fermentation technologies to develop innovative biomolecules.
Dr Kiran Mazumdar-Shaw, Chairman and Managing Director of Biocon, said, "I believe that Biocon through its partnership with Neopharma, will contribute to the growth and development of this country in the field of biotechnology."
Dr Shetty said Neopharma has reached a break-even point after 18 months of operations.
[This is not only Dubai - it is INDIA with Dubai. Put them on the map of PostGenetics - comment on the 10th of January, 2007 by A. J. Pellionisz]
Science Daily Researchers at Johns Hopkins have discovered that a tiny piece of genetic code apparently goes where no bit of it has gone before, and it gets there under its own internal code.
A report on the renegade ribonucleic acid, and the code that directs its movement, will be published Jan. 5 in Science.
MicroRNAs, already implicated in cancer and normal development, latch on to and gum up larger strands of RNA that carry instructions for making the proteins that do all the cell's work. They are, says Joshua Mendell, M.D., Ph.D., an assistant professor in the McKusick-Nathans Institute of Genetic Medicine at Hopkins, like "molecular rheostats that fine-tune how much protein is being made from each gene."
That's why normally microRNAs always have appeared to stick close to the cell's protein-making machinery.
But during a survey of more than 200 of the 500 known microRNAs found in human cells, Mendell's team discovered one lone microRNA "miles away" --- in cellular terms --- from all the others.
"It was so clearly in the wrong place at the wrong time for what we thought it was supposed to be doing that we just had to figure out why," says Hun-Way Hwang, a graduate student in human genetics and contributor to the study.
Consisting of only 20 to 25 nucleotide building blocks (compared to other types of RNA that can be thousands of nucleotides long), each microRNA has a different combination of blocks. Mendell's team realized that six building blocks at the end of the wayward miR-29b microRNA were noticeably different from the ends of other microRNAs.
Suspicious that the six-block end might have something to do with miR-29b's location, the researchers chopped them off and stuck them on the end of another microRNA. When put into cells, the new microRNA behaved just like miR-29b, wandering far away from the cell's protein-making machinery and into the nucleus, where the cell's genetic material is kept.
The researchers then stuck the same six-block end onto another type of small RNA, a small-interfering RNA or siRNA that turns off genes. This also forced the siRNA into the nucleus.
According to Mendell, these results demonstrate for the first time that despite their tiny size, microRNAs contain elements consisting of short stretches of nucleotide building blocks that can control their behavior in a cell. Mendell hopes to take advantage of the built-in "cellular zip code" discovered in miR-29b as an experimental tool. For example, he plans to force other microRNAs and siRNAs into the nucleus to turn off specific sets of genes.
Mendell's team is actively hunting for additional hidden microRNA elements that control other aspects of their behavior in cells. They also are curious to figure out what miR-29b is doing in the nucleus. Because microRNAs have been implicated in cancer as well as normal development, Mendell hopes that further study of miR-29b will reveal other, hidden functions of microRNAs.
Hun-Way Hwang,1 Erik A. Wentzel,2 Joshua T. Mendell1,2*
MicroRNAs (miRNAs) negatively regulate partially complementary target messenger RNAs. Target selection in animals is dictated primarily by sequences at the miRNA 5' end. We demonstrated that despite their small size, specific miRNAs contain additional sequence elements that control their posttranscriptional behavior, including their subcellular localization. We showed that human miR-29b, in contrast to other studied animal miRNAs, is predominantly localized to the nucleus. The distinctive hexanucleotide terminal motif of miR-29b acts as a transferable nuclear localization element that directs nuclear enrichment of miRNAs or small interfering RNAs to which it is attached. Our results indicate that miRNAs sharing common 5' sequences, considered to be largely redundant, might have distinct functions because of the influence of cis-acting regulatory motifs.
[PostGenetics at its best! microRNA-s composed of PLE-s (pyknon-like-elements)? What the miR-29b might be doing in the nucleus (where the DNA is...) may be a tell-tale (pun intended) sign that protein-synthesis is an inherently recursive iteration process - comment on the 6th of January, 2007 by A. J. Pellionisz]
Genomics Back in Favor in Q4
"Illumina led the resurgence in the technology, tools and genomics companies in 2006. Millennium Pharmaceuticals, Human Genome Sciences, Curagen and Celera Genomics all posted high double digit gains in their share prices for the year," added Burrill.
"The transition to a more personalized medicine world is creating the need for molecular diagnostics, biomarkers, genotyping assays, etc. and so companies specializing in these areas have received positive investor attention," he continued. "Sequenom, for example, a provider of fine mapping genotyping, methylation and gene expression analysis solutions, saw its share price rocket and closed the year up 588%."
The Burrill Genomics Index surged 14% in Q4 06 and although this gain failed to bring the Index back into positive territory, closing the year down 13%, there is every reason to believe that companies in the genomics space will have a successful 2007 driven by the industry's need for faster and more expansive genotyping technology to scan genes that will reveal clues to curing diseases.
Investors Still Positive on Biotech
"While biotech's performance in the capital markets waxed and waned throughout the year, at the mercy of prevailing macro-economic forces, concern for Iraq, elections/politics, and about healthcare cost increases, it was a big year for biotech/life sciences fund raising. Financings and partnering deals brought in a record $47 billion for US companies with over $27 billion through financings and $20 billion in partnering capital."
In total biotech raised $6.2 billion in 4Q 06, picking up the pace again after Q3 06, which saw only $2.4 billion collectively raised by the industry. Leading the way were follow-ons and debt financings. The $1.7 billion debt financings in Q4 06 put an exclamation mark on what has been a remarkable year. With almost $14 billion raised in 2006, the total debt capital generated by the industry represents what was raised in the whole of 2004 and 2005 combined. [This puts a perspective on the news that Korea WILL invest in 10 years $14 billion. The USA has invested already that much in a single year. As predicted by Juan Enriquez, the global competition will wipe out those regions that fail to meet "the genomics challenge" - AJP]
Leading the pack of over 20 deals in the quarter was Celgene, which grossed $1,032 billion from a public offering of 20 million shares of its common stock at $51.60 per share.
Selected Secondaries during Q4 06:
Company Amount ($M)
Arena Pharmaceuticals 175
Regeneron Pharmaceuticals 175
Alexion Pharmaceuticals 149
Ariad Pharmaceuticals 145
Advanced Magnetics 130
Alnylam Pharmaceuticals 101
Positive quarter for biotech IPOs
In the fourth quarter biotech IPO activity picked up with six deals getting out of the gate. The $350 million raised from these transactions was up a whopping 614% over the Q3 06 total. In fact, the Q4 06 total was the most accumulated since Q2 04, when $580 million was generated from IPOs. Financings from IPOs in 2006 were up 12% over the 2005 amount. Even more welcome news was the highly successful IPO debut of Affymax. Not only did the company price its opening day share price above its expected offering range late in December, but its share price jumped 36% in the final few trading days before the end of the month. The company's lead product, Hematide, is poised for Phase III trials. It is an erythropoiesis-stimulating agent that, if proven safe and effective, may improve the management of anemia and offer patients and physicians an alternative therapy to recombinant erythropoietin products currently on the market.
US IPOs during 2006:
Company Ticker Offer IPO Issue Price % Amount
Range date Price 12/29/06 Change Raised
Altus ALTU $14-16 Jan $15 $18.85 25.67% $121
Iomai Corp. IOMI $11-13 Jan $7 $4.98 -28.86% $35
SGX SGXP $11-13 Jan $6 $3.50 -41.67% $25
Acordia ACOR $11-13 Feb $6 $15.84 164.00% $36
Valera VLRX $10-12 Feb $9 $8.10 -10.00% $35
Alexza ALXA $10-12 Mar $8 $11.39 42.38% $44
Omrix OMRI $15-17 Apr $10 $30.26 202.60% $39
Targacept TRGT $11-13 Apr $9 $9.05 0.56% $45
Vanda VNDA $12-14 Apr $10 $24.65 146.50% $58
BioMimetic BMTI $11-13 May $8 $13.19 64.88% $36.8
Novacea NOVC $11-13 May $6.50 $5.66 -12.92% $45
Replidyne RDYN $14-16 Jun $10 $5.74 -42.60% $45
Osiris OSIR $11-13 Aug $11 $25.32 130.18% $38.5
Achillon ACHN $14-16 Oct $11.50 $16.11 40.09% $59.5
Cadence CADX $11-13 Oct $9 $12.32 36.89% $54
Trubion TRBN $13-15 Oct $13 $18.01 38.54% $52
Catalyst CPRX $11-13 Nov $6 $4.83 -19.50% $20
Emergent EBS $14-16 Nov $12.50 $11.16 -10.72% $57.8
Affymax AFFY $22-24 Dec $25 $34.04 36.16% $106
(19 companies) $12-14 $10.13 $14.37 40.11% $50.14
Venture Capital: Deal Flow Continues Its Healthy Pace
The amount of venture capital generated by biotechs remained steady in Q4 06 when compared to the Q3 06 period. Although there were two fewer reported deals in the quarter, for the 45 that got done -- the average deal size of $22 million was $2 million higher per investment. Year-over-year, the $4.1 billion raised in 2006 was up 18% on the $3.5 billion generated in 2005.
Selected venture financings during Q4 06:
Company Amount ($M)
Solstice Neurosciences 85
Cerenis Therapeutics 53.5
Magellan Biosciences 50
Concert Pharmaceuticals 48.5
Elixir Pharma 46
Neurotech Pharma 35
Orexigen Therapeutics 30
Xanthus Pharma 25
San Diego based Kalypsys Inc. raised $100 million in a Series C financing. It plans to use the proceeds to fund a broad range of preclinical and clinical programs in the areas of cardiovascular/metabolic diseases, pain/inflammation and oncology. Solstice Neurosciences, Inc., received a combined $85 million in Series B equity funding and debt financing. The funds will support the company's ongoing initiatives related to movement disorders and treatment for cervical dystonia using Myobloc (Botulinum Toxin Type B) Injectable Solution.
Deal Making Remains Red Hot...
However, the bigger story -- and one that has been unfolding for the past two years, is the amount the industry has generated through partnering. The $20 billion raised is an all time record amount for partnering in biotech's 30+-year history, surpassing the then record setting $17 billion total in 2005.
"Partnering deals set a new mark in biotech's comparatively short history and is a continuing testimony that big pharma's enthusiasm for doing deals with biotechs is not slowing down," said Burrill. Financings garnered in partnering deals during Q4 2006 were up a whopping 74% compared with Q3 06 and the amount raised fell just short of the record-setting $7.7 billion that was recorded in the comparable Q4 05 period.
Grabbing the deal making headlines in the quarter was GlaxoSmithKline, signing a deal, worth potentially $2.1 billion, with Genmab A/S to co-develop and commercialize HuMax- CD20 (ofatumumab), a fully human monoclonal antibody in late stage development for CD20 positive B-cell chronic lymphocytic leukemia and follicular non-Hodgkin's lymphoma and in Phase II for rheumatoid arthritis. Epix Pharmaceuticals also signed a lucrative worldwide multi-target strategic collaboration with GlaxoSmithKline to discover, develop and market novel medicines targeting four G-protein coupled receptors for the treatment of a variety of diseases, including Epix's 5-HT4 partial agonist program, PRX-03140, in early-stage clinical development for the treatment of Alzheimer's disease. Epix will receive total initial payments of $35 million and be eligible to earn potential milestones of up to $1.2 billion.
Roche was also active...Halozyme Therapeutics, Inc. and Roche entered into an agreement to apply Halozyme's Enhanze drug delivery technology based on recombinant human hyaluronidase (rHuPH20) to Roche's biological therapeutic compounds. InterMune, Inc. closed an exclusive license agreement with Roche for the worldwide development and commercialization of InterMune's hepatitis C virus (HCV) protease inhibitor program. InterMune received an upfront payment of $60 million and Roche will fund 67% of the development costs associated with ITMN-191, InterMune's lead HCV protease inhibitor drug candidate. Assuming the successful development and commercialization of ITMN-191 in the US and other countries, InterMune could receive up to $470 million in milestones.
...And So Were M&As
Multi-billion dollar acquisitions were the order of the day for big pharma and large cap biotechs during the final quarter of the year. This was biotech's second active year in a row in terms of buyouts, as large biotechnology and pharmaceutical companies went beyond licensing agreements to fill out development and product pipelines.
"We haven't seen this many deals in any year between pharma/ biotech and biotech/biotech in the industry's history," noted Burrill. "The huge premiums that big pharma is willing to pay for biotech innovation reflects their pipeline problems. Compared to the daunting $1.2 -- $1.8 billion that is needed to bring a new drug to market and the long 10-15 years development cycle, paying big premiums, even for drugs that are not even in the clinic, is both a cheap and efficient way of reducing development costs and shortening commercialization timelines for the pharma acquirers," said Burrill."
Abbott broadened its portfolio of products for lipid management with a $3.7 billion acquisition of specialty pharmaceutical company Kos Pharmaceuticals. Gilead Sciences Inc. bought Myogen for $2.5 billion and Genentech, Inc. acquired Tanox Inc., a biotechnology company specializing in the discovery and development of biotherapeutics based on monoclonal antibody technology, for approximately $919 million. The companies have been working together in collaboration with Novartis since 1996 to develop and commercialize Xolair(R), an anti-IgE monoclonal antibody approved by the FDA in 2003 as a treatment for patients with moderate-to-severe allergic asthma. The deal also helped Genentech improve its pipeline in the areas of asthma, HIV, and age-related macular degeneration.
Illumina, Inc., was also in deal-making mood mode picking up gene sequencing platform company Solexa, Inc. in a stock-for-stock merger valued at around $600 million.
"The M&A trends, that have been hot in 2005 and 2006 in biotech land, will not slow down with pharma still desperate to access pipeline and innovation, " commented Burrill. "Both big pharma and big biotech will be competing for companies with advanced product pipelines, as well as important land grabs of technology such as the $1.1B acquisition of Sirna by Merck announced in November."There will also be no slow down in partnering deals and a significant portion of the $20 billion that we project that will be raised in 2007 will be directed at gaining access to technology at an earlier stage in its development as companies strengthen their product indication franchises."
Selected M&A transactions announced during Q4 06:
Acquirer Acquired Value ($M)
Abbott Kos Pharmaceuticals 3700
Eli Lilly Icos 3200
Gilead Myogen 2500
Merck Sirna Therapeutics 1100
Genentech Tanox 919
Illumina Solexa 660
Genzyme AnorMED 584
[The "big picture" of "Pharma" going for "tech>to>pharma" by acquisition, shows the Merck/Sirna deal of $1.1 Billion only in the "middle range" - and as shown by the newsclip below, even the doubling of value over six months may not be enough for shareholders, with sixfold increases in a year reported in fine genome analysis, methylation tools. - comment on the 5th of January, 2007 by A. J. Pellionisz]
Sirna's Shaky Shareholder Settlement Sheds Light on Merck Acquisition
[January 4, 2007]
NEW YORK (GenomeWeb News) Merck last week closed its $1.1 billion acquisition of Sirna Therapeutics, but not before the RNAi shop managed to tentatively muzzle a trio of shareholder-led lawsuits accusing its brass of double-dealing in their negotiations with Merck, according to a filing with the Securities and Exchange Commission.
The resulting settlement-in-principle, which Sirna said can fall apart at any time, compelled Sirna to disclose information about how it negotiated the deal, which showed that it had been in negotiations with another company about a possible buyout.
According to the SEC filing, Sirna said it would reduce to $38 million from $42.1 million the termination fee it would have been required to pay Merck if the deal fell through.
The settlement-in-principle also requires Sirna to make additional disclosures to its investors to address the issue of whether its management sought the best price possible for the company when it negotiated the acquisition.
According to Sirna, after the company had received an initial offer from Merck late last year, it received a written offer from another, undisclosed, company proposing to acquire Sirna for between $10 and $12 a share, which was higher than Merck’s original offer.
Merck later sweetened its offer to $13 a share, which was “higher than the highest range of any third-party offer,” Sirna noted in the SEC filing. Additionally, “no other interested party submitted a proposal after Merck’s final proposal was received,” the company said.
The settlement-in-principle also calls for Sirna to pay $500,000 to the plaintiffs’ legal counsel to cover fees and expenses.
“We and the other defendants vigorously deny all liability with respect to the facts and claims alleged in the lawsuits,” Sirna said in the SEC filing, dated Dec. 20, 2006. “However, to avoid the risk of delaying or otherwise imperiling the merger, and to provide information to our stockholders at a time and in a manner that would not cause any delay of the merger, we and our directors agreed to the settlement.
As originally reported by GenomeWeb News sister publication RNAi News, three shareholders filed separate lawsuits last year attempting to block the sale and accused Sirna’s management of negotiating the deal for their own financial benefit.
The suits allege that Merck’s purchase of Sirna “is wrongful, unfair, and harmful to Sirna’s public stockholders, and represents an effort by [Sirna’s directors] to aggrandize their own financial position and interests” at the expense of ordinary shareholders.
The lawsuits specifically charge that Sirna’s President and CEO Howard Robin and the firm’s board members violated their fiduciary duties “insofar as they stood on both sides of the transaction and engaged in self-dealing and obtained for themselves personal benefits, including personal financial benefits.”
Sirna’s directors “are unwilling to share the lion’s share of [the company’s potential success] with the company’s shareholders, choosing instead to sell the company to Merck … and cash out Sirna shareholders for inadequate consideration,” the lawsuits charge
[We raised the question writing about the SIRNA/MERCK deal"who made the best deal?" in our universe of leveraging, merger & acquisition. The rule is, "the higher level is the deal, the higher the profits are". Thus, it may not be surprising that "average stockholders" may wish to see a better deal, e.g. by themselves acquiring smaller, budding entities that THEY can leverage... - comment on the 3rd of January, 2007 by A. J. Pellionisz]
Richard J. Jackson* and Nancy Standart*
Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK.
Abstract: Several thousand human genes, amounting to about one-third of the whole genome, are potential targets for regulation by the several hundred microRNAs (miRNAs) encoded in the genome. The regulation occurs posttranscriptionally and involves the ~21-nucleotide miRNA interacting with a target site in the mRNA that generally has imperfect complementarity to the miRNA. The target sites are almost invariably in the 3'-untranslated region of the messenger RNA (mRNA), often in multiple copies. Metazoan miRNAs were previously thought to down-regulate protein expression by inhibiting target mRNA translation at some stage after the translation initiation step, without much effect on mRNA abundance. However, recent studies have questioned these suppositions. With some targets, an increase in the rate of mRNA degradation by the normal decay pathway contributes to the decrease in protein expression. miRNAs can also inhibit translation initiation, specifically the function of the cap-binding initiation factor, eIF4E. Repressed target mRNAs as well as miRNAs themselves accumulate in cytoplasmic foci known as P-bodies, where many enzymes involved in mRNA degradation are concentrated. However, P-bodies may also serve as repositories for the temporary and reversible storage of untranslated mRNA, and reducing the expression (knockdown) of several distinct P-body protein components can alleviate miRNA-mediated repression of gene expression.
["Imperfect complementarity"? Perhaps in the sense of strict sequentiality as defined in modern Genetics. The fractality or miRNA and the target may be the clue to "complementarity" - as defined in PostGenetics, the postmodern era of Genetics - comment on the 3rd of January, 2007 by A. J. Pellionisz]
[The beginning of 2007 is perhaps well characterized by an account of a blog reader, who focuses on science of "junk" DNA, minimizing polemics of interpretation, but strong on citing reasonably respectable sources. On one hand, this article quotes Richard Dawkins, who is very much against ID - comment by AJP]:
...“And there's lots more DNA that doesn't even deserve the name pseudogene. It, too, is derived by duplication, but not duplication of functional genes. It consists of multiple copies of junk, "tandem repeats", and other nonsense which may be useful for forensic detectives but which doesn't seem to be used in the body itself.””…
Panda’s Thumb also finds it important to argue for “Junk DNA”:
[This far it looks like "what else is new" - the Evolution and ID camps are at each others' throat. However, the rest of this article - fortunately - is remarkably devoid of "name calling" or even "debate for debate's sake", but is focused on "the evidence pouring in from molecular biology and genetics research". - This is a wonderful change compared to "superheated pseudodebates" that we saw recently, e.g. in Time magazine. On this Science column; "Altogether now" - let's focus on the science! - comment by AJP]
Tandem Repeats are a class of repetitive DNA unique in every individual, which is why they are used in DNA forensic evidence, etc. … Talk Origins also has this to say about Tandem Repeats: “scientists view tandem repeat sequences as resulting from accidental DNA duplications.”
Now let’s look at what the scientific evidence is telling us about Tandem Repeats:
This region contains the major and minor promoters of the Tsix gene, which runs antisense to Xist, and the
DXPas34 tandem repeat lying close to the Tsix major promoter.
Our results identify a function for DXPas34 in murine XCI and demonstrate the critical role of Tsix transcription in preventing XCI in differentiating male ES cells and in normal functioning of the counting pathway.
Transfection studies in mouse mesenchymal C3H10T1/2 cells showed that it is the tandem repeat of the C/EBP binding site in PPARgamma2 promoter region that regulates dexamethasone-mediated PPARgamma2 gene activation.
These observations establish that a dinucleotide tandem repeat sequence, capable of self-association, forms part of a cell-specific silencer element in a mammalian gene.
They [tandem repeats] Determine the Length of a Dog’s Nose
Breeds with collie-like noses had more of a particular tandem repeat, while those with pug-like faces had more of a different tandem. And when the researchers compared bull terrier DNA, they found that terriers have one more repeat unit than they did in the 1950s, which could explain why the nose used to be droopier, the researchers note.
They [tandem repeats] Determine a Cow’s Milk Fat Percentage
In addition to this, another polymorphism in the 5'-regulatory region of this gene, the DGAT1 variable number of tandem repeat (VNTR), also showed a strong association with milk fat percentage.
These research finding show that, far from being junk, Tandem Repeats have important functional roles in the genome. More interestingly, the unique copy number in individuals seems not to be caused by random mutations, but rather by a built-in program that occurs during the combination of male and female DNA. While children will tend to inherit Tandem Repeat numbers similar to those of their parents, this variable component makes every child unique. The fact that Tandem Repeats are so well correlated to racial classifications shows that they have a role in determining what each individual looks like. Tandem repeats appear to be the major factor in what determines the size of your nose, the amount of body fat you have, your height, skin color, etc.
Here’s what Talk Origins says about Transposons:
In many ways, transposons are very similar to viruses. However, they lack genes for viral coat proteins, cannot cross cellular boundaries, and thus they replicate only in the genome of their host. They can be thought of as intragenomic parasites.…finding the same transposon in the same chromosomal location in two different organisms is strong direct evidence of common ancestry, since they insert fairly randomly and generally cannot be transmitted except by inheritance….
So is there evidence that Transposons have function?
The research, published in the October issue of Developmental Cell, suggests that retrotransposons may not be just the "junk DNA" once thought, but rather appear to be a large repository of start sites for initiating gene expression. Therefore, more than one third of the mouse and human genomes, previously thought to be nonfunctional, may play some role in the regulation of gene expression and promotion of genetic diversity. Dr. Barbara B. Knowles and colleagues from The Jackson Laboratory in Bar Harbor, Maine, found that distinct retrotransposon types are unexpectedly active in mouse eggs, and others are activated in early embryos. Surprisingly, by acting as alternative promoters, retrotransposon-derived controlling elements drive the coordinated expression of multiple mouse genes. The researchers think that expression of retrotransposons during very early stages may contribute to the reprogramming of the mammalian embryonic genome, a prerequisite for normal development.
Generic repeated signals in the DNA format expression of coding sequence files and organize additional functions essential for genome replication and accurate transmission to progeny cells. Retroelements comprise a major fraction of many genomes and contain a surprising diversity of functional signals.
That is just the beginning. Now let’s examine specific classes of Transposons mentioned in the two Talk Origins Articles.
The Talk Origins view of SINEs/Alu:
…current evidence suggests that only a very few Alu sequences are active sources of transcripts; perhaps transcription from most copies is inhibited by the chromosomal environment of the insertion
Further, the excellent health of individuals who lack particular Alu insertions supports the view that these insertions do not serve any important function in human physiology.
What does the recent scientific evidence say about SINEs/Alu?
Through a process called alternative splicing, humans create multiple versions of a gene and, consequently ,multiple proteins. It’s a way of constructing a new protein, while keeping a backup copy of the original version.For example, the researchers found that the ADAR2 enzyme contains 40 amino acids in its active site that arederived from an Alu element. The addition changes the activity of the enzyme.
"The excitement about the exonization of Alu is the ability to explain what is unique in our genome," Ast says. The mouse genome contains 2.5 billion nucleotides, the human genome around 3 billion. "The quarter of a billion nucleotides, [or] the difference between human and mouse, is mostly [due to] retrotransposable elements like Alu," he says.
Although Alu was originally thought to represent ‘junk’ having no biological functions, the presence of Alu sequences within protein-coding genes can affect the processing of mRNAs at multiple levels
Extensive conservation of V-SINEs can, however, be more easily explained by the hypothesis that the central conserved domain may somehow "earn its keep" in the genome.
The observed conservation strongly indicates that the central domain of these transposable elements have been exapted, i.e., have become a functional component of the mammalian genomes.
The close copies of the ultraconserved element scattered around vertebrate genomes have changed less than would be expected over evolutionary time, indicating that they are functionally important. But relatively few of the copies contain parts that code for proteins, which suggests they [ultraconserved elements] instead are helping to regulate when genes are turned on and off.
“Thus, AmnSINE1 appears to be the best example of a transposable element of which a significant fraction of the copies have acquired genomic functionality.”
So many SINES have been shown to be FUNCTIONAL, counter to the Talk Origins claims. Alu sequences are unique to primates and seems to be particularly active in the human brain.
Talk Origins has this to say of LINES:
LINEs thus have several properties expected of "selfish" DNA sequences that can spread in the host DNA simply because they encode their own machinery for spreading.
In other words, they don’t serve a purpose other than to copy themselves, according to Talk Origins.
Here’s what some recent scientific evidence says about LINES:
Long interspersed elements (LINE-1, L1s) are the only active autonomous retrotransposons in mammals, covering as much as 18% of their genomes. L1s' activity results in a great repertoire of actions, such as gene disruption, transcriptional regulation, alternative splicing, creation of exons and gene coding regions and amplification of the processed pseudogenes and the Alu SINE family.
In summary, we have identified a LINE-2 fragment named ALF that is a potent T-cell-specific silencer. We also show that agonists that down-regulate ALF-containing genes in T cells induce a factor that binds to a sequence within ALF. These findings are in contrast to other reports associating enhancer or promoter activities with repetitive elements (16,17), because ALF has the potential to function as a cell-type-specific silencer. We favour the hypothesis that this is not an arbitrary activity, and that ALF contributes to gene regulation in vivo.
Because L1 is an abundant and broadly distributed mobile element, the inhibition of transcriptional elongation by L1 might profoundly affect expression of endogenous human genes. We propose a model in which L1 affects gene expression genome-wide by acting as a 'molecular rheostat' of target genes. Bioinformatic data are consistent with the hypothesis that L1 can serve as an evolutionary fine-tuner of the human transcriptome.
Thus, our results suggest that LINE-1s can integrate into DNA lesions, resulting in retrotransposon-mediated DNA repair in mammalian cells.
Extrapolating these findings to the 600,000 copies of L1 in the genome, we predict that the amount of DNA transduced by L1 represents ~1% of the genome, a fraction comparable with that occupied by exons. So again, there are plenty of examples now of functional LINES.
Endogenous Retroviruses and LTR retrotransposons
Talk Origins has this to say of Endogenous Retroviruses:
Endogenous retroviruses are molecular remnants of a past parasitic viral infection. Occasionally, copies of a retrovirus genome are found in its host's genome, and these retroviral gene copies are called endogenous retroviral sequences. Essentially all of these endogenous retroviruses contain mutations that would disrupt the function of their genes, as would be expected if they inserted millions of years ago with no selective pressure to maintain the function of the genes.
Here’s what some recent scientific evidence says about Endogenous Retroviruses:
Human tissues that lack HERV transcription could not be found, confirming that human endogenous retroviruses are permanent components of the human transcriptome. Distinct activity patterns may reflect the characteristics of the regulatory machinery in these cells, e.g., cell type-dependent occurrence of transcriptional regulatory factors.
In particular, a class of endogenous retroviruses, known as endogenous retroviruses related to Jaagsiekte sheep retrovirus or enJSRVs, are critical during the early phase of pregnancy when the placenta begins to develop.
Indeed, the LTR is the dominant promoter in the colon, indicating that this ancient retroviral element has a major impact on gene expression
EBR LTR promotes a significant proportion of the total EBR transcripts, and transient transfection results indicate that the LTR acts as a strong promoter and enhancer in a placental cell line. They are highly conserved between the mouse and distantly related species…. On account of their abundance, LTR retrotransposons are believed to hold major significance for genome structure and function.…High sequence similarity between several LTR retrotransposons identified in this study and those found in distantly-related species suggests that horizontal transfer has been a significant factor in the evolution of mouse LTR retrotransposons.
The discovery that human-specific retroviruses emerged at the same time other researchers believe humans and chimps diverged was startling.…McDonald said it is increasingly clear that organisms need the viral elements and that their apparent continual backdoor assaults on normal genes may, in truth, be more like a vast, sophisticated chess game on an enormously complex board. Admittedly, most of the scientists involved in the above studies of Endogenous Retroviruses still assume that they were parasites that somehow were incorporated into the genome with functional roles. However, since many of these perform similar functions in different species, one cannot prove common descent based upon the idea that shared retroviruses are shared errors.
Both the Talk Origins and Panda’s Thumb websites spend a lot of time on Pseudogenes.
Thus, pseudogenes - and especially retrotransposed pseudogenes - are generally considered to be non-functional relics and, together with other sorts of repetitive and “selfish” DNA elements, as well as other unique DNA sequences, form the so-called “junk DNA”. (For a more general discussion of “junk DNA”, see Ian Musgrave’s discussion….) Indeed, when the pseudogenes can be followed over evolutionary lineages, they appear to evolve neutrally, accumulating mutations progressively and freely until they become almost unrecognizable, or disappear from the genome altogether. Note that the number of pseudogenes in the human genome (20,000 or so at the latest count, many of them crippled viral elements) is comparable to that of our functional genes - an impressive amount. Where does this leave us with regard to pseudogenes? Actually, pretty much where we were before the Gray paper came out….The evidence still overwhelmingly supports the notion that many, likely most pseudogenes are functionless, and it does so regardless of the validity of Hirotsune’s findings. Indeed, if one assumes that evolutionary conservation of DNA sequences is a strong hallmark of potential function, then a recent study by a Swedish group shows that at best a few dozens of the thousands of pseudogenes in the human and mouse genomes are under sufficient selective pressure to be highly conserved between the two lineages, suggesting they may be functional . Still, there is ample room for potential interesting mechanisms by which pseudogenes can on occasion be recruited into regulatory and structural functions.
So is the case really closed regarding pseudogenes? Based upon the review of the available literature I’ve done, it appears that the folks at Panda’s Thumb and Talk Origins are spending all of their time gloating over past victories and missing the forest of evidence showing that many Pseudogenes are functional, or that the term Pseudogene is incorrectly applied to a large portion of the DNA.…
In evolutionary conserved regions, 90% of pseudogenes appear to be under regulation. Note also that the Panda’s Thumb article assumes that Methylation means “inactivity”/non-function, while these researchers conclude it implies regulatory function.
They discovered that regions called evolutionary conserved regions (ECRs), lying distant from genes, out in the ‘junk’ DNA, had high concentrations of methylation. This may indicate that these regions have an undiscovered role to play in gene or chromosome activity, according to the scientists. In addition, analysis of methylation led the team to portions of DNA previous thought to be relatively inactive. Some portions of DNA, known as pseudogenes, appear to have lost function or their exact function is unknown because they have not yet been experimentally studied. Researchers found that these regions were approximately 90 percent methylated, leading them to suspect that methylation might contribute to the inactivity of such genes.
Although four examples of Type-1 retroposons were previously reported [25,43], types 2 and 3 are characterized here for the first time. Several Type-3 snoRTs originating from ribosomal protein genes were previously annotated as processed pseudogenes, but their intronic parts (snoRNA sequence and downstream intron) were overlooked since the pseudogenes were identified by alignment of cDNA or peptide sequences with genomic sequences
The NANOG Pseudogene family is touted …as an example of common descent between Humans & Chimps. … research has shown that the NANOG Pseudogenes 1 & 8 appear to have regulatory roles...
The most effective short double-stranded RNA corresponded to a sequence shared by NANOG and the duplication pseudogene, NANOGP1. This would suggest that NANOGP1 transcript, despite not being translated into a protein, would be downregulated as result of the RNAi approach.
The expression of NANOGP8 in cancer cell lines and cancer tissues suggests that NANOGP8 may play important roles in tumorigenesis. This work not only has potential significance in stem cell and cancer research, but it also raises the possibility that some of the human pseudogenes may have regulatory functions.
Surprisingly, we also identified transcription from the genomic region previously thought to encode the pseudoalpha2 gene. The source of that transcription is characterized in this report as a previously unrecognized globin gene.
KLK31P is a novel androgen regulated and transcribed pseudogene of kallikreins that may play a role in prostate carcinogenesis or maintenance.
Pseudogene inhibits tumor growth - may have other roles
Based on our findings, PsiCx43 joins and enlarges the thus far restricted group of functionally transcribed and translated pseudogenes.
A survey of the genomic context of more than 300 human miRNA loci revealed that two primate-specific miRNAs,miR-220 and miR-492, each lie within a processed pseudogene.
Through analysis of the mouse genome, we also found that an Oct4 pseudogene was located in the same locus as Nanog, Stella, and GDF3 on chromosome 6. Moreover, the relative positional order of these genes was conserved between the mouse and human genomes. By BLASTing the EST data base we found that this mouse pseudogene islikely transcribed, as an exact sequence hit was generated (data not shown). This suggests that the mouse oct4 pseudogene, which colocalizes with Nanog, Stella, and GDF3 is transcriptionally functional.
...assumptions about pseudogenes have been largely mistaken. Even when pseudogene sequences are different in different species (not conserved), this doesn’t necessarily prove that they are non-functional. Instead, these could be regulatory sequences where the differences are part of the explanation of why species are unique in the first place. Does this mean that truly non-functional Pseudogenes don’t exist? No. … If a gene is no longer needed for something it used to do as part of original design, then it is likely to become non-functional. For example, when fish species move into caves, they lose the ability to see and lose their skin pigmentation in a relatively small number of generations, since neither of those features are necessary to survive in a dark cave. It is no surprise that the genes and/or regulatory DNA associated with those become non-functional as well over time. Sean Pitman has further information about Pseudogenes at is excellent website “The Emperor Has No Clothes” at:
If there is any good reason why biologists were under the assumption that much DNA must be Junk, it would be the CValue Enigma (or C-Value Paradox), which is mentioned briefly in the Talk Origins “shared errors” article. Basically, the Enigma is that “genome size does not correlate with organismal complexity” as discussed in ... Wikipedia:
At first blush, the C-Value Enigma would seem to imply that much DNA in some eukaryotic species is redundant at best. However, there is now evidence for correlation between C-Value and organismal complexity, and also valid reasons for extra copies of DNA in certain species, as discussed in the following scientific research:
For all of the data sets examined here, there are significant positive correlations between genome size or numbers of open reading frames and numbers of cell types and numbers of types of cell parts. These results suggest that the greatest irony about the C-value paradox may very well be that there is no paradox at all and that genome complexity and morphological complexity actually do significantly positively correlate with one another, at least for the organisms with sequenced genomes in this data set.
As is apparent from the brief review given above, the relationship between genome size and erythrocyte size isdetectable in each of the vertebrate classes, even in the uniquely enucleate case of mammals. There are many ways in which erythrocytesize is of relevance to organismal biology. Larger RBCs contain more hemoglobin, but they also require larger blood vessels. Species with large cells also typically have fewer cells. Blood viscosity, total hemoglobin content, and other such parameters are of obvious significance to organismal physiology, but no other parameter has received more attention in regards to genome size/cell size interactions than erythrocyte surfacearea to volume (SA:V) ratios.
It is not clear based on the present dataset whether or not the stronger association in animals is of any functional significance, but it is nevertheless obvious that rDNA copy number and genome size are strongly related in these organisms. The necessity for this abundance of rDNA has been attributed to the fact that, unlike protein-coding genes, it cannot undergo secondary rounds of amplification via translation when organisms require more rRNA transcripts.
The researchers have determined that the injury frequency depends on the size of genome: the larger the size it, the lower the frequency is. So, large genome serves protection from injuries.
“Junk DNA” becomes “The Transcriptome”
So now that we’ve shown that all of the classes of Junk DNA touted by Talk Origins can have functional roles, let’s conclude this discussion with some of the latest findings regarding non-coding DNA including the complexity ….
The findings of the FANTOM3/Genome Network project
This issue of PLoS Genetics includes a special collection of articles that explore the transcriptome complexity being revealed by work on the FANTOM3 dataset. Besides revealing staggering complexity, analysis of this collection is providing an increasing number of novel mRNA classes, expressed pseudogenes, and bona fide noncoding variants of protein-coding genes. These studies force a paradigm shift in the understanding of the transcriptome. First, the studies find that 63% of the genome is transcribed from at least one strand (in contrast to the earlier belief that only 2% of the genome is transcribed into protein-coding mRNAs). Second, an unexpected amount of variation was found in alternative splice forms (65% of all transcriptional units [TUs] contain alternatively splicing variants), TSSs (which identify promoters), and polyadenylation sites. Frith and colleagues have extended the analysis of noncoding transcript expression and have identified 10,000 full-length cDNAs derived from expressed pseudogenes - constituting approximately 10% of the known transcriptome - half of which are promoted by retrotransposons, or otherwise characterized promoters, and are likely to participate in various regulatory mechanisms.
This study provides an unprejudiced survey of “pathological” RNA molecules, which resemble protein-coding RNA except that they contain violations of the genetic code. These pseudomessenger RNAs constitute a surprisingly large fraction of all transcripts, as much as 10%. These ghostly molecules have always been present in RNA surveys, but have stayed below the radar because they do not cleanly correspond to annotated elements in DNA, i.e., “genes”. Their prevalence demonstrates that RNA is a distinct continent that cannot be fully understood as a mirror of DNA or proteins.
Non-protein-coding RNAs (ncRNAs) are increasingly being recognized as having important regulatory roles. Although much recent attention has focused on tiny 22- to 25-nucleotide microRNAs, several functional ncRNAs are orders of magnitude larger in size. Examples of such macro ncRNAs include Xist and Air, which in mouse are 18 and 108 kilobases (Kb), respectively.
As stated earlier - it is the Non-Coding DNA that makes species unique
As discussed in this article, the non-coding transcribed part of the genome increases dramatically in size with the complexity of organisms, culminating in an estimated 1.2 billion nucleotides in humans
It is clear that much of what was once termed ‘junk’ DNA represents highly evolved, functional sequence containing amongst other things, numerous transcriptional regulatory motifs.
"Not so many years ago our understanding was that DNA was transcribed to RNA, which was then translated to protein. Now we know that the levels of control are much more varied and that many RNAs don't make protein, but instead regulate the expression of proteins," Davidson explained. "Non-coding RNA like microRNAs represent a set of refined control switches, and understanding how microRNAs work and how they are themselves controlled is likely to be very important in many areas of biology and medicine."
Junk DNA - the biggest mistake in the history of biology
Even as many scientists are finding function in the “junk”, their logic is still clouded by evolutionary reasoning. For example, rather than just accepting Transposons as functional, this article concludes that RNA editing sites are trying to protect the genome from Transposons. “We used to believe there were only a limited number of RNA editing sites,” she says, “but now we think there may be as many as 20,000 sites involving perhaps 3,000 genes. Interestingly, most of the editing sites correlate with non-coding regions of DNA, the so-called junk DNA.” “Transposons occupy as much as half of our entire genome, and they can be dangerous,” Nishikura says. “As a result, mechanisms have arisen through evolution to suppress their activity. This is particularly true in the egg and sperm, where maintenance of the genome’s integrity is critical.” I believe such reasoning will eventually be squashed as the evidence of the Transcriptome is revealed. Unlike the…statements of Richard Dawkins, Talk Origins, and PT, at least some biologists are able to … admit what has been happening in biology for the past 30 years:
“I think this will come to be a classic story of orthodoxy derailing objective analysis of the facts, in this case for a quarter of a century,” Mattick says. “The failure to recognize the full implications of this-particularly the possibility that the intervening noncoding sequences may be transmitting parallel information in the form of RNA molecules- may well go down as one of the biggest mistakes in the history of molecular biology.”
Shared “Junk DNA” was supposed to be something that could only be explained by evolution. Now that that argument is gone, let’s build our case further…. First up are highly conserved areas of the DNA between all species. While evolutionists may argue that this shows common descent, it is just as easily argued that a common designer would use the same components. More telling, there are many examples where higher species (e.g. humans) share identical DNA with single-celled organisms. If evolution is constantly improving on things over time, why would species that have been separated by hundreds of millions of years (per the evolutionary timeline) still share identical DNA? A better answer is that these critical systems are so highly specified, they must have been optimal from the start, and so evolution has no answer for how they could have arisen from some sub-optimal precursor. There are thousands of examples of highly conserved DNA, and we offer a few examples below:
Thus, the interplay of these three proteins to provide the optimal level of accuracy of translation has been conserved during the 2 billion years of evolution that separate E. coli from S. cerevisiae.
Sec1/Munc18 (SM) proteins comprise a small family of cytoplasmic proteins that play a pivotal role in intracellular membrane fusion. They are structurally highly conserved in evolution, and each SM protein is specialized for a single or a small group of trafficking steps. SM proteins of evolutionarily distant species that are involved in the same trafficking steps are capable of replacing each other whereas within one organism, different SM proteins show no functional redundancy
...We found 202 genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements are dramatically changed in human but not in other primates, with seven times more substitutions in human than in chimp. To identify changes that may be functional, we focus on the set of regions of the human genome of at least 100 base pairs (bp) that appear to have been under strong negative selection up to the common ancestor of human and chimp (as evidenced by high sequence identity between chimp and rodents), but exhibit a cluster of changes in human compared to chimp. Our expectation is that the selective constraint on the most extremely accelerated regions of the human genome may have switched from negative to positive (and possibly back to negative) some time in the last 5−6 million years.
HAR1 has only two changes in its 118 letters of DNA code between chimpanzees and chickens. But in the roughly five million years since we shared an ancestor with the chimpanzees, 18 of the 118 letters that make up HAR1 in the human genome have changed.
HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal-Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex.
The scientists identified networks of genes that correspond to specific brain regions. When they compared these networks between humans and chimps, they found that the gene networks differed the most widely in the cerebral cortex -- the brain's most highly evolved region, which is three times larger in humans than chimps. Secondly, the researchers discovered that many of the genes that play a central role in cerebral cortex networks in humans, but not in the chimpanzee, also show significant changes at the DNA level.
One thing is becoming clear: proteincoding genes may not be the movers and shakers of human evolution scientists once thought. “We should stop looking at proteins and start looking at noncoding DNA,” says Lunter. “Everything points in that direction.”
So, here we have DNA that is so important in brain development that it is nearly identical in all other animals tested, but radically different in humans. In this particular area, chimps are much more closely “related” to chickens and rodents than to humans. Look at the… statements this forces those committed to evolution to make “the most extremely accelerated regions of the human genome may have switched from negative to positive (and possibly back to negative) some time in the last 5−6 million years.” Said another way, the only evolutionary explanation is that there was DNA so important to the brain that any change in it was not tolerated in any other species, but somehow in the line leading to humans change was beneficial. Then, once it reached a certain point, the changes to humans stopped again. ...
For additional accumulating evidence that humans are unique compared to other species, read on:
"The idea that microRNAs can contribute to species identity has been bandied about for some time, and this is nice confirmation of that," said Zamore. "We're beginning to home in on what makes us, us." Now, researchers at the Hubrecht Laboratory in Utrecht, the Netherlands, have combed painstakingly through theRNA in human and chimp brains, and found 447 new micro-RNAs, more than doubling the number discovered so far (Nature Genetics, DOI: 10.1038/ng1914). Some were expressed very rarely. "The brain has 10,000 cell types," says team member Edwin Cuppen. "Perhaps that is because of all these micro-RNAs." Many were unique to chimps and humans, and some only to humans. So even though we share most of our DNA with chimps, small genetic changes that fine-tune its expression might account for the radical differences in our brains.
"We've proven that there is a big distinction. Human evolution is, in fact, a privileged process because it involves a large number of mutations in a large number of genes," Lahn said. "To accomplish so much in so little evolutionary time a few tens of millions of years requires a selective process that is perhaps categorically different from the typical processes of acquiring new biological traits." The making of the large human brain is not just the neurological equivalent of making a large antler. Rather, it required a level of selection that's unprecedented," Lahn said. "Our study offers the first genetic evidence that humans occupy a unique position in the tree of life."
The human brain is not just a scaled-up version of a mammal brain or even of an ape brain. “All told, it seems that the human brain may be more dynamic than ape or monkey brains”, says Preuss. “The human brain seems to be running hot in all sorts of ways.”
A lot more genes may separate humans from their chimp relatives than earlier studies let on. Researchers studying changes in the number of copies of genes in the two species found that their mix of genes is only 94 percent identical. The 6 percent difference is considerably larger than the commonly cited figure of 1.5 percent.
Conclusion [the reader should reach his/her own - in 2007 let's focus on Science - comment on the 3rd of January, 2007 by A. J. Pellionisz]
Whole-genome association studies.
The trickle of studies comparing the genomes of healthy people to those of the sick is fast becoming a flood. Already, scientists have applied this strategy to macular degeneration, memory, and inflammatory bowel disease, and new projects on schizophrenia, psoriasis, diabetes, and more are heating up. But will the wave of data and new gene possibilities offer real insight into how diseases germinate? And will the genetic associations hold up better than those found the old-fashioned way?
[The "Junk DNA diseases" (PostGenetic Medicine) era started in 2005 with IPGS, posting also a website on "junk DNA diseases" and the "Forbes" article a year ago. In 2006, New York Times picked up the topic. In late February, another Forbes article drove home the medical significance of microRNA-s (as well as a California-Israel cooperation, to be followed by California-Germany alliance). In late March, industrial "whole genome tools", especially focusing on SNPs (single nucleotide polymorphisms) helped disease and whole genome association studies - only to be conceptually upset by the major breakthrough of presenting 66 million short repetitive sequences ("motifs") with 128 thousand more strictly defined "pyknons" in late April by Rigoutsos of IBM. This, in part, "made biology an information science" (Eric Lander), and the mined short repetitive sequences (first, microRNA-s) became of commercial value e.g. between Israel and Germany (and Israel and USA, ibid), as well as to explore disease-associations, Rigoutsos established an MIT-Singapore alliance. Short repetitive sequences composing fractal structures became associated with a slew of diseases , where specificity is currently under exploitation. It was in this spirit, that the notion of "junk" DNA has been formally abandoned at the "European Inaugural" of IPGS by the 12th of October, 2006. As a major setback to "SNPs", 1/8 of the (human) genome was found to be diverse - making it much more likely that small repetitive segments (rather than single nucleotides) are preserved as clues to whole genome function. As the year ended to wrap-up, 3 Nobels were awarded to the underlying science, and Merck realized a 30 billion dollars valuation increase by investing 1 billion dollars into therapy based on short repetitive sequences. While most of the above tumultuous developments came too late to "Science" and thus "only" #6,7,10 items of its "top 10" relate to "junk DNA", the above terse "forecast" by Science "to watch in 2007" for "disease associations of the whole genome" is likely to make 2007 "the year of PostGenetics" - comment by A.J. Pellionisz, 30th of December, 2006. ]
Sirna shareholders approve $1.1 billion sale of company to Merck
[oops, the price of short repetitive sequences just skyrocketed...]
Posted on Thu, Dec. 28, 2006
SAN FRANCISCO - Shareholders of Sirna Therapeutics Inc. on Thursday approved the sale of the tiny biotechnology company to the pharmaceutical company Merck & Co. for $1.1 billion.
In October, the Whitehouse Station, N.J.-based Merck announced it had offered Sirna shareholders $13 per share for a company attempting to turn a Nobel Prize-winning technology into medicines.
The offer represented a 102 percent premium over Sirna's closing stock price on Oct. 30. The stock's previous high for the past year is $8.52, set in April.
Sirna is one of at least half a dozen biotech companies developing drugs that silence genes by interfering with the messenger-carrying RNA. The technique was discovered by this year's Nobel winners, Andrew Fire of Stanford University and Craig Mello at the University of Massachusetts.
The San Francisco company said the acquisition is expected to close when "reasonably practicable."..
[Business Week adds: "Merck made the offer Oct. 30 for the company, which focuses on RNA Interference, or gene silencing technology. Treatments using the technology target the gene at the root of a disease and aim to make it inactive, thus stopping the disease." The Revolution in PostGenetic Medicine aside, let's glimpse a little into the economics. Sirna was worth half as much before the deal started to brew. Fire and Mellow (Nobel Prized discoverers of the technology) got $0.6 Million (each). Sirna shareholders (the tiny San Francisco firm whose stocks bottomed at about a single dollar in 2003, raked in half a billion valuation-increase in the last few months). Merck (with its Zocor patent expired mid-summer...), took a one billion dollar gamble. Looking at its stock chart, the market cap of German Merck (close to a hundred billion dollars) went up roughly 30 percent in the course of the gamble. That is about thirthy billion dollars, an increase of thirty times by one billion dollars in investment (in the course of 6 months). All this before an entirely novel crop of drugs cames out, that (in spite of their price) might not cure, but will be stopping the disease (if so, patients would have to take them for life). Question: "who got the best deal in this classic case of 'leveraging'" in the era of PostGenetics? - comment by A.J. Pellionisz, 29th of December, 2006. ]
Small RNA molecules that shut down gene expression have been hot, hot, hot in recent years, and 2006 was no exception. Researchers reported the discovery of what appears to be a new and still-mysterious addition to this exclusive club: Piwi-interacting RNAs (piRNAs). Abundant in the testes of several animals, including humans, piRNAs are distinctly different from their small RNA cousins, and scientists are racing to learn more about them and see where else in the body they might congregate.
PiRNAs made their grand entrance last summer, when four independent groups released a burst of papers describing them. In a sense, their sudden prominence is not surprising. The Piwi genes to which piRNAs bind belong to a gene family called Argonaute, other members of which help control small RNAs known as microRNAs (miRNAs) and small interfering RNAs (siRNAs). Scientists already believed that the Piwi genes regulate the development and maintenance of sperm cells in many species. With the discovery of piRNAs, they may be close to figuring out how that happens.
Particularly intriguing to biologists is the appearance of piRNAs: Many measure about 30 RNA bases in length, compared with about 22 nucleotides for miRNAs and siRNAs. Although that may not sound like much of a difference, it has gripped biologists and convinced them that piRNAs are another class of small RNAs altogether. Also striking is the molecules' abundance and variety. One group of scientists found nearly 62,000 piRNAs in rat testes; nearly 50,000 of those appeared just once.
But beyond characterizing what piRNAs look like and finding hints that they can silence genes, scientists are mostly in the dark. Still to be determined: where they come from, which enzymes are key to their birth, and perhaps most important, what they do to an organism's genome.
[2006 was, in fact, the year when the notion 'Junk' DNA was officially abandoned. Yet, while #6,7 and #10 on the "top 10" of Science's list pertained to declaring an old axiom a dogma, with #10 about piRNAs, the old saying was justified, again: "Facts don't kill theories - only better new theories kill old theories". As long as some new algorithmic theories making sense of the whole DNA (with RNA playing a role in recursive iteration) are not "targeted" at least as a straw-man, facts only accumulate - but the 'junk' notion is implicitely alive - comment by A.J. Pellionisz, 28th of December, 2006. ]
Science 22 December 2006:
Vol. 314. no. 5807, p. 1892
[kept for half a billion years]
Byrappa Venkatesh,1* Ewen F. Kirkness,2* Yong-Hwee Loh,1 Aaron L. Halpern,3 Alison P. Lee,1 Justin Johnson,3 Nidhi Dandona,1 Lakshmi D. Viswanathan,3 Alice Tay,1 J. Craig Venter,3 Robert L. Strausberg,3 Sydney Brenner1
Cartilaginous fishes represent the living group of jawed vertebrates that diverged from the common ancestor of human and teleost fish lineages about 530 million years ago. We generated ~1.4x genome sequence coverage for a cartilaginous fish, the elephant shark (Callorhinchus milii), and compared this genome with the human genome to identify conserved noncoding elements (CNEs). The elephant shark sequence revealed twice as many CNEs as were identified by whole-genome comparisons between teleost fishes and human. The ancient vertebrate-specific CNEs in the elephant shark and human genomes are likely to play key regulatory roles in vertebrate gene expression
[Half a billion years could not squeeze out a "non-coding" sequence? It must be doing something worthwile keeping ... With this spectacular finding Craig Venter and Nobelist Sydney Brenner joined the league of not only "ultraconserved elements" (led by Haussler and Mattick), but by implication there is hardly any important figure in Genomics who would not agree that the epiphet "Junk" must be put at rest. Fig. is from "Support material"- comment by A.J. Pellionisz, 22nd of December, 2006. ]
RNA silencing or RNA interference (RNAi) is a recently discovered process involving RNA molecules, in which, as the name indicates, these molecules interfere and shutdown specific genes.
And now, while studying the mechanism behind RNAi researchers at Oxford and Helsinki University have discovered that the functional core of a key enzyme (enzymes are proteins which promote biochemical reactions in the body) involved in the formation of RNAi molecules is striking similar to an enzyme involved in gene expression.
The research, published in the journal "Public Library of Science Biology", supports the idea that the two enzymes have a common ancestor and gives weight to the theory that life started as self-replicating RNA molecules in a RNA world (as opposed to the present world where molecules of DNA are the basis of life).
In fact, we live in a DNA world, as genes are segments of DNA, and it is the information contained in the genes of an organism that, when translated into proteins, makes up the blueprint for the body structure and function. This process, the expression of genes into proteins, is comprised of two steps: the first by which genetic information in DNA is converted into RNA and the second which is the synthesis of proteins based on the information/instructions contained in the newly made RNA (DNA ? RNA ? protein).
But there is a dent in this apparently perfect process. In fact, for a long time scientists have been puzzled why approximately 32% of the human genome/DNA, although transformed into RNA, does not lead to protein production (DNA ? RNA ? no protein)? So why would this huge amount of “junk” RNA keep being formed instead of being eliminated during evolution? After all, a basic rule of life is that any reaction that costs energy and is not advantageous for the individual must be eliminated. What recent research unveiled is that RNA is a much more multifaceted molecule than previously thought, and some of that “junk” RNA actually plays an important role in gene regulation. One such example is RNAi, a RNA that is capable of blocking the activity of specific genes.
And it was while studying the mechanisms behind RNAi, that Paula S. Salgado, Jonathan M. Grimes and colleagues discovered that the functional core of an enzyme involved in the formation of short RNAi molecules from other RNA molecules (RNA? RNA), was remarkably similar to the one that mediates the formation of RNA from DNA (DNA ? RNA) during the first step of gene expression. This striking similarity suggested a common ancestor and further analysis seemed to indicate that the enzyme involved in the RNAi process had appeared before and so would probably be more similar structurally to the common ancestor.
These results support the idea of life starting in a (RNA) world where self-replicating (RNA?RNA) multifunctional RNA molecules evolved (as well as the enzymes mediating the process) into the present situation where genetic information is contained instead on DNA. In fact, although RNA is chemically similar to DNA it has, as the “originater” of life, two major advantages over the latter molecule: 1- it is easily synthesised from non-complex blocks so it had higher possibility of occurring spontaneously and 2 - it is easy to imagine that it could evolve into DNA, which by being a much more stable molecule would then take over. Furthermore, the idea of a primitive RNA world, if proved, could solve one of biggest conundrums on the origin of life: if life needs both DNA as a source of genetic information and proteins to drive life’s chemical reactions how could have one appeared first without the other? Some scientists believe that the answer lies in this ancient RNA molecule which was capable of supporting life reactions and also contained life’s genetic blueprint and whose existence seems to be consistent with the findings of Salgado, Grimes and colleagues.
In this way, Salgado’s work sheds light not only on the mechanism behind this extremely interesting and important process that is RNAi, but can also help to understand better how life began on earth.
[If this is not a "PostModern" view in Genetics (PostGenetics) - one wonders what is... In the full text of scientific paper the emphasis is much less "journalistic" it is a very deep molecular study of the 3-D structure of RNAi. One would welcome e.g. the elaboration of "information system theory" implications - comment by A.J. Pellionisz, 21st of December, 2006. ]
Quite a lot of buzz in the journals these days challenging the views that variations that generate phenotypic differences occur in a more or less random manner and that most, if not all, non-coding DNA has no biological function. More and more evidence shows that genomes are in fact reservoirs of "adaptive phenotypic plasticity". This might go along with the concept of front-loaded evolution which predicts, in my opinion, that adaptive benefits are likely to occur at greater than random frequencies.
Recent findings that the primary source of genome-size variation is in fact repetitive DNA (Brenner et al. 1993; Kidwell 2002) has led to lots of interesting research into the roles and functions of repetitive loci. For example, Biémont & Vieira (2006) and Volff (2006) focus on transposable elements (TEs), and Kashi & King (2006) review the contribution of microsatellite loci.
Tracing the evolutionary history of repetitive elements through the study of nucleotide sequences shows that most, if not all, repetitive DNA is derived from TEs: in Drosophila and Cetaceans (Kidwell 2002), centromeric repeats have been traced to TEs in plants (Henikoff et al. 2002); and microsatellites have been observed to come from TEs in organisms as diverse as fruit flies (Wilder & Hollocher 2001), mosquitoes (Tu et al. 2004), barley (Ramsay et al. 1999) and humans (Deininger & Batzer 2002).
Evidence that transposable elements donate repetitive sequences with unique biological functions to their host organisms (reviewed by Britten 1997; 2006; Biémont & Vieira 2006; Volff 2006) provokes questions about the roles and functions of other repetitive DNA loci. Specific responses to environmental cues have been detected at repetitive loci other than TEs in plants (Ceccarelli et al., 2002), bacteria (Servant, Grandvalet & Mazodier 2000; Kojima & Nakamoto, 2002; Ojaimi et al., 2003) and humans (Uhlemann et al. 2004), indicating that these loci retain the capacity for generation of phenotypic variation.
If environmentally induced beneficial RE mutations are to have evolutionary significance, they must also be passed to subsequent generations. Environmentally mediated changes in REs have been reported in a range of taxa, but most well-known examples focus on situations where phenotypic effects are negative. Little thought seems to have been given to the possibility that such mutations might also have positive effect. This is an open avenue of investigation.
Caporale (2000) has indicated that heritable genomic responses to recurrent classes of environmental challenge are in fact a key mechanism of adaptive evolution. Evidence that repetitive DNA elements are at least one source of such mutations is strong:
- Mutations in and/or transposition of repetitive DNA affect structure and expression of coding genes in many diverse species and play essential roles in fundamental biological processes.
- REs tend to cluster in genes, or genomic regions, involved in or associated with externally triggered processes and show a unique capacity to respond to environmental signals.
- Site-specific mutations at and/or transposition of repetitive loci are associated with adaptive changes of phenotype in natural populations.
Such findings suggest that genomes are composed of genetic units that are larger, and more complex, than previously thought. Rather than being determined by simple point mutations in protein-coding regions, most phenotypic variation is generated and maintained by complex combinations of variation within larger systems comprised of both coding and non-coding elements.
[For full references, click on the title. This write-up is the contemporary version of what Dr. Simons claimed from the Darwinian viewpoint since 1987, pointing out that most Darwinists were wrong to deny function to e.g. 98.7% of the human DNA. It is also consistent with the general trend of shifting away from SNPs (point mutations) toward "compositional patterning". The article stops short of naming the mathematical nature of the algorithm; fractal geometry, as in FractoGene - comment by A.J. Pellionisz, 15th of December, 2006. ]
Annual Fifteen Thousand Million US dollars to them. This is about 810 times the money of the Nobel Prize... For six years, close to 5,000 times the Nobel Prize money...
Korea plans to invest $14.3 billion in biotechnology research and industrialization over the next 10 years to create a $60 billion market by 2016.
This market will push the nation to No. 7 worldwide, from its current ranking of No. 14.
The ambitious plan was unveiled by the Ministry of Science and Technology Wednesday.
The ministry’s ``Bio-Vision 2016’’ plan puts priority on the acquisition of core technologies and the establishment of infrastructure that will help them in the applied industry, a ministry spokesman said.
The detailed plan calls for the integration of bio-technology with related areas such as post-genome studies, gene-to-life research, information technology and nano-technology.
Meanwhile, the ministry selected the two ``National Scientists,’’ who will be entitled to the annual financial research support of 1.5 billion won for up to six years. ...
[Juan Enriquez was absolutely right predicting in his bestseller "As the future catches you" that after "digital" the next challenge will be "genomics" that will catapult (or sink...) some regions and countries - comment by A.J. Pellionisz, 15th of December, 2006. ]
By INGFEI CHEN
New York Times: December 12, 2006
Thirty years ago, Nick Patterson worked in the secret halls of the Government Communications Headquarters, the code-breaking British agency that unscrambles intercepted messages and encrypts clandestine communications. He applied his brain to “the hardest problems the British had,” said Dr. Patterson, a mathematician.
Today, at 59, he is tackling perhaps the toughest code of all the human genome. Five years ago, Dr. Patterson joined the Broad Institute, a joint research center of Harvard and the Massachusetts Institute of Technology. His dexterity with numbers has already helped uncover startling information about ancient human origins.
In a study released in May, scientists at the Broad Institute scanned 20 million “letters” of genetic sequence from each of the human, chimpanzee, gorilla and macaque monkey genomes. Based on DNA differences, the researchers speculated that millions of years after an initial evolutionary split between human ancestors and chimp ancestors, the two lineages might have interbred again before diverging for good.
The controversial theory was built on the strength of rigorous statistical and mathematical modeling calculations on computers running complex algorithms. That is where Dr. Patterson contributed, working with the study’s leader, David Reich, who is a population geneticist, and others. Their findings were published in Nature.
Genomics is a third career for Dr. Patterson, who confesses he used to find biology articles in Nature “largely impenetrable.” [This is the biggest challenge; without intimate cooperation of biology- and mathematically minded leaders, with a proven record of fruitful cooperation, result is often vasteful or even alienating - AJP]. After 20 years in cryptography, he was lured to Wall Street to help build mathematical models for predicting the markets. His professional zigzags have a unifying thread, however: “I’m a data guy,” Dr. Patterson said. “What I know about is how to analyze big, complicated data sets.” [Actually, by today's standards, a genome can be amazingly small. Human DNA is smaller than a video you rent from Netflix, and e.g. the entire genome of the Mycoplasma fits on a floppy disk (that is so small that nobody uses it anymore). The non-coding fraction of the entire Mycoplasma genome is less than 50k - even a stamp-sized low quality digital picture is much larger amount of information. Complex? "Complexity is in the eye of the bevildered". - AJP]
In 2000, he pondered who had the most interesting, most complex data sets and decided “it had to be the biology people.”
Biologists are awash in DNA code. Last year alone, the Broad Institute sequenced nearly 70 billion bases of DNA, or 23 human genomes’ worth. Researchers are mining that trove to learn how humans evolved, which mutations cause cancer, and which genes respond to a given drug. Since biology has become an information science, said Eric S. Lander, a mathematician-turned-geneticist who directs the Broad Institute, “the premium now is on being able to interpret the data.” That is why quantitative-minded geeks from mathematics, physics and computer science have flocked to biology.
Scientists who write powerful DNA-sifting algorithms are the engine driving the genomics field, said Edward M. Rubin, a geneticist and director of the federal Joint Genome Institute in Walnut Creek, Calif. Like the Broad, the genome institute is packed with computational people, including “a bunch of astrophysicists who somehow wandered in and never left,” said Dr. Rubin, originally a physics major himself. Most have never touched a Petri dish.
Dr. Patterson belongs to this new breed of biologist. The shelves of his office in Cambridge, Mass., carry arcane math titles, yet he can converse just as deeply about Buddhism or Thucydides, whose writings he has studied in ancient Greek. He is prone to outbursts of boisterous laughter.
He was born in London in 1947. When he was 2 his Irish parents learned that he had a congenital bone disease that distorted the left side of his skull; his left eye is blind. He became a child chess prodigy who earned top scores on math exams, and later attended Cambridge, completing a math doctorate in finite group theory. In 1969, he won the Irish chess championship.
In 1972, Dr. Patterson began working at the Government Communications Headquarters, where his research remains classified. He absorbed through his mentors the mathematical philosophy of Alan Turing, the genius whose crew at Bletchley Park the headquarters’ predecessor broke Germany’s encryption codes during World War II. The biggest lesson he learned from Dr. Turing’s work, he said, was “an attitude of how you look at data and do statistics.”
In particular, Dr. Turing was an innovator in Bayesian statistics, which regard probability as dependent upon one’s opinion about the odds of something occurring, and which allows for updating that opinion with new data. In the 1970s, cryptographers at the communications headquarters were harnessing this approach, Dr. Patterson said, even while academics considered flexible Bayesian rules heretical.
In 1980, Dr. Patterson moved with his wife and children to Princeton, N.J., to join the Center for Communications Research, the cryptography branch of the Institute for Defense Analyses, a nonprofit research center financed by the Department of Defense. His work earned him a name in the cryptography circle. “You can probably pick out two or three people who’ve really stood out, and he’s one of them,” said Alan Richter, a longtime scientist at the defense institute.
In 1993 Dr. Patterson moved to Renaissance Technologies, a $200 million hedge fund, at the invitation of its founder, James H. Simons, a mathematician and former cryptographer at the institute. The fund made trades based on a mathematical model. Dr. Patterson knew little about money, but the statistical methods matched those used in code breaking, Dr. Simons said: analyzing a series of data in this case daily stock price changes and predicting the next number. Their methods apparently worked. In Dr. Patterson’s time with the hedge fund, its assets reached $4 billion.
By 2000, Dr. Patterson was restless. One day, he ran into Jill P. Mesirov, another former defense institute cryptographer, and mentioned his interest in biology. Dr. Mesirov, then director of computational biology at the Whitehead/M.I.T. Center for Genome Research, which later became the Broad Institute, hired him.
“Really, what we do for a living is to decrypt genomes,” Dr. Mesirov said. Cryptographers look at messages encoded as binary strings of zeros and ones, then extract underlying signals they can interpret, Dr. Mesirov said. The job calls for pattern recognition and mathematical modeling to explain the data. The same applies for analyzing DNA sequences, she said.
One common genomic analysis tool the Hidden Markov Model was invented for pattern recognition by defense institute code breakers in the 1960s, and Dr. Patterson is an expert in that technique. It can be used to predict the next letter in a sequence of English text garbled over a communications line, or to predict DNA regions that code for genes, and those that do not.
Dr. Patterson said he also has a well-honed instinct about which data is important, after seeing “a lot of surprising stuff that turned out to be complete nonsense.” Dr. Lander of the Broad Institute describes him as a great skeptic, with the statistical insight to tell whether a signal is “simply random fluctuation or whether it’s a smoking gun.”
Making that distinction is one of the great difficulties of interpreting DNA. In studying the human-chimp species split, the genomics researchers strove to rule out possible errors and biases in the data.
Dr. Reich, with Dr. Patterson and Dr. Lander, and two other colleagues, used computer algorithms to compare the primate genomes and count DNA bases that did not match, like the C base in gorillas that had become an A in humans. Because such mutations naturally arise at a set rate, the researchers could estimate how long ago the human and chimp lineages separated from an ancient common ancestor.
A DNA base can mutate more than once, however. To correct for that, Dr. Patterson worked out equations estimating how often it occurred; Dr. Reich revised their computer algorithms accordingly. Two strange patterns emerged. Some human DNA regions trace back to a much older common ancestor of humans and chimps than other regions do, with the ages varying by up to four million years. But on the X chromosome, people and chimps share a far younger common ancestor than on other chromosomes.
After the researchers tested various evolutionary models, the data appeared best explained if the human and chimp lineages split but later began mating again, producing a hybrid that could be a forebear of humans. The final breakup came as late as 5.4 million years ago, the team calculated.
The project was “our hobby” Dr. Reich said of himself and Dr. Patterson said. Their main work, in medical genetics, includes devising a shortcut to scan the genome for prostate cancer genes.
Whether studying disease or evolution, Dr. Patterson noted, genomics differs from code breaking in one key respect: no adversary is deliberately masking DNA’s meaning. Still, given its complexity, the code of life is the most open-ended of cryptographic challenges, Dr. Patterson said. “It’s a very big message.”
["There is nothing simpler than a problem solved" (Faraday) - Statistics is the first cut in sorting out what is has low or high probability. With the genome, we already know that there is a high probability of finding "patterns" (they are all over). Pattern recognition algorithms abound (e.g. in Neural Networks - with the Bayesian and Hidden Markov algorithms as examples. The question is what "self-similar" repetitive patterns (also found and shown by Rigoutsos et al. "pyknon"-s) convey? The predilection of this commentator (with a record of interdisciplinary cooperative results) is known: the fractality of the genome and organismal development it governs reduces the problem into manageable proportions, and both experimentally verifiable quantitative predictions have been supported, and material bases for fractal recursive iterative protein-synthesis (FractoGem-s) have been found (mined and identified to correlate with specific non-coding DNA diseases). - comment by A.J. Pellionisz, 13th of December, 2006. ]
From Tuesday's Globe and Mail
Craig Venter, the controversial American scientist whose company mapped a private version of the human genome and pushed the public project to match his spitfire pace, is about to show the world exactly what he's made of.
The 60-year-old Dr. Venter says he has finished decoding his DNA, which would make him the first person on the planet able to read, if not fully understand, his own operating instructions.
"We're about to publish the first complete genome that's ever been done," Dr. Venter said in a recent interview in Toronto. "It just so happens that it's my genome."
DNA is the genetic code we carry in our cells, spelling out in six billion chemicals our bodies' master plan -- from the slope of a forehead to the arch of a foot.
Dr. Venter's DNA has told him he's not likely to fall ill with mad-cow disease any time soon. But he could go blind or lose his mind to Alzheimer's, if heart disease doesn't kill him first.
While lunching at the Four Seasons Hotel, he was careful with the menu, picking chicken curry over beef, just as he opts for oatmeal breakfasts and takes cholesterol-lowering drugs.
"My cholesterol was never extremely high, but based on this increased genetic risk, why not try this?" said Dr. Venter, who plans to make his DNA freely available online. "The point is that you can take charge with a preventative medicine paradigm, and hopefully that will be the future."
Some may dismiss Dr. Venter's genetic full Monty as the ultimate form of exhibitionism. But the blue-eyed entrepreneur believes his personal genome project signals the start of a new era that will eventually allow all people to learn the secrets of their codes and tailor their health care to suit their genes.
"There are about six billion people for whom having my genome is of little value," he acknowledged. "But to me, it's of great value . . . and that's what it really gets down to -- the individual."
The more individual genomes researchers collect, he noted, the better able they will be to interpret them. "Knowing what I'm susceptible to and what I'm not doesn't help you, it's true. But having several thousand genomes, this helps us all."
The public human genome map and the one finished in 2000 by Dr. Venter's former company, Celera Genomics, were compilations of different DNA donors. But both maps represented only half genomes -- since they decoded only one chromosome from each of the 23 pairs a person inherits from their parents.
"That's why we've done this new version that we think will be the reference," Dr. Venter said.
But it won't be the last. Several academic groups and companies are racing to find the most cost-effective way to accurately decode the genome of a single person, a technical feat that involves figuring out the sequence of the three billion chemical base pairs, or six billion nucleotides, that make up DNA.
Connecticut biotech firm 454 Life Sciences is at work on the genome of James Watson, the Nobel laureate who co-discovered the structure of DNA in 1953. In October, the California non-profit X Prize Foundation announced a $10-million (U.S.) reward -- put up by Canadian diamond hunter Stu Blusson -- to the first group that can quickly and cheaply decode the genomes of 100 people in 10 days. Celebrities such as astrophysicist Stephen Hawking, television interviewer Larry King, Google co-founder Larry Page and Paul Allen, the co-founder of Microsoft, have already signed up.
Harvard University has launched a Personal Genome Project that plans to recruit at least 10 DNA donors. One of its many goals is to develop a cost-effective technology to decode a genome for as little as $1,000.
"The [amount of DNA] you can get for one dollar is doubling every year," said project head George Church, director of Harvard's Center for Computational Genetics. "A lot of people are thinking, 'Oh, this is dreamy stuff that may be possible 10 years from now. But I fully believe that subsets [of moderately affordable information] will be ready next year."
Dr. Venter estimates that his genome project has cost roughly $10-million. It's been sequenced by a small army of computer scientists and geneticists at the J. Craig Venter Institute in Rockville, Md., the non-profit centre where Dr. Venter has worked since leaving Celera over a business dispute in 2002.
His sequence still contains a few gaps and few people outside the group have seen it. But one who has, Steve Scherer, a senior scientist at Toronto's Hospital for Sick Children, said that, "By all definitions, it's a pretty complete product." Based on information he's received, it appears to be about 97-per-cent complete, Dr. Scherer said.
In November, Dr. Scherer, who is leading a team in the running for the X Prize, was co-author of the landmark discovery that the number of genes humans carry can vary more wildly than expected. Dr. Venter's group has since asked him to collaborate on their project and analyze Dr. Venter's DNA for these anomalies.
"From a technical standpoint, [Dr. Venter's genome] marks a huge milestone," said Dr. Scherer, who visited the Maryland lab last week. "I think most people in the community believe that the trend will be to sequence DNA for both research and diagnostics."
But the prospect of going public with a personal genome is not without risks. Experts have long pointed out that such information could, for example, be used by insurance firms to deny coverage or increase premiums, or by companies to refuse employment.
A former government researcher, Dr. Venter has built a reputation for daredevil tactics, from kick-starting a race for the human genome to combing the world's oceans for energy producing microbes and starting work on the first synthetic life form -- a lab-made bacterium.
But Dr. Venter played down the personal dangers of unveiling his DNA. He pointed out that part of his genome has already been available, albeit for a hefty fee through Celera.
"That was part of my goal, to show that it wasn't all that risky to have your genome sequenced.
"My life has not been laid bare by having my genome analyzed," said Dr. Venter, who plans to include his genetic information in A Life Decoded, a memoir to be published next spring. He expects the academic paper on his genome to appear by early next year.
In fact, he feels that the benefits of decoding his DNA far outweigh the risks for himself, his siblings and his grown son (an artist now training to become a scientist).
For example, Dr. Venter started taking a cholesterol-lowering drug after learning he carries a gene type that puts him at higher risk of heart disease.
The same gene linked to heart disease has been loosely associated with a higher risk of developing Alzheimer's disease and he also carries a gene type that increases his risk of developing macular degeneration by 40 per cent.
But relatives have since told him that he has no family history of age-related blindness or Alzheimer's.
"Maybe they all died from heart disease before they could get Alzheimer's," he mused, "or macular degeneration."
Dr. Venter's father died of a heart attack at 59. But his mother, he says, is still active in her mid-80s.
Scientists are still trying to determine which genes he inherited from his mother and which ones came from his father.
But Dr. Venter uses the examples to stress the point that it's dangerous to attribute too much power to genes. Most gene types linked to disease, or particular traits, he said, are based on "a range of statistical probabilities."
"Here I have my whole genome, and a whole staff of highly qualified geneticists and it's still hard to interpret," said Dr. Venter, who has been pushing Washington to pass a genetic non-discrimination bill.
"We measure the genetic code because we can, not because it's the only important thing," he said. Eventually, "it will help us to know how important the environment is."
Indeed -- although Dr. Venter does not carry a gene mutation believed to increase the risk of skin cancer, he has had melanoma. And the gene type linked to risk-taking? Ironically, Dr. Venter's DNA doesn't carry that either.
[Larry Page of Google and Paul Allen of Microsoft - let alone Craig Venter - entrepreneurs who all signed up for "personalized medicine" know full well that there will be a huge market, once the costs will be lowered. Just like with "home computers" while many were scratching their heads why would anyone need a computer at home - (the same) Microsoft plunged into making billions by producing the OS without which no hardware could function; "SafeDNA" is available to provide a solution for the "privacy problem" - comment by A.J. Pellionisz, 12th of December, 2006 .]
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