(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
(03 Oct) The Nobel Prize in Chemistry for 2006 is awarded to Roger Kornberg
(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...]
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. ]
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. ]
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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