At least 80% of the human genome is functional, scientists now say, based on a genetic survey called ENCODE that may force reassessment of what a gene is.
The big news in human genetics this week is the publication of results by the ENCODE (Encyclopedia of DNA Elements) consortium, “the most ambitious human genetics project to date,” and what it reveals about function in the human genome. When the human genome was first published, scientists were surprised that only about 3% of it coded for proteins. That was before they knew about all the coded information in the “epigenome,” which includes RNA transcripts that regulate the code. The new results show that at least 80% of the human genome is, in fact, functional, rendering the evolutionary notion of “junk DNA” (leftovers from our evolutionary past) incorrect. Evolutionists themselves are writing the “eulogy for junk DNA.”
There is so much buzz about this story that came out in Nature this week, all we can do is list some of the more prominent headlines. References to Nature are from the 6 September 2012 issue, volume 489, no. 54. Popular reports in the news media are too numerous to list.
- Nature’s news feature “ENCODE: The Human Encyclopaedia” by Brendan Maher begins, “First they sequenced it. Now they have surveyed its hinterlands. But no one knows how much more information the human genome holds, or when to stop looking for it.”
- Evolution is mentioned in some of the Nature papers, but after notions of “evolutionarily conserved” and “evolutionary constraints” are removed (which refer to lack of evolution), what is left is mostly assumption rather than discovery. In Nature’s summary article “Genomics: ENCODE Explained,” one mention of evolution was not particularly helpful to Darwinists: “Why evolution would maintain large amounts of ‘useless’ DNA had remained a mystery, and seemed wasteful,” Barroso wrote. “It turns out, however, that there are good reasons to keep this DNA.” Then Barroso listed some of the good things the non-coding DNA does. In the section “Evolution and the Code,” two of the authors stashed most of the understanding in the future: “many aspects of post-transcriptional regulation, which may also drive evolutionary changes, are yet to be fully explored.” The other three authors did not mention evolution.
- Nature looked back at a quote by Nobel laureate David Baltimore 11 years ago when the human genome was first published: “Unless the human genome contains a lot of genes that are opaque to our computers, it is clear that we do not gain our undoubted complexity over worms and plants by using many more genes. Understanding what does give us our complexity — our enormous behavioural repertoire, ability to produce conscious action, remarkable physical coordination (shared with other vertebrates), precisely tuned alterations in response to external variations of the environment, learning, memory … need I go on? — remains a challenge for the future.” Now, Peter Bork and Richard Copley state that the ENCODE data “may offer insight into function and regulation beyond the level of individual genes. The draft is also a starting point for studies of the three-dimensional packing of the genome into a cell’s nucleus. Such packing is likely to influence gene regulation … The human genome lies before us, ready for interpretation.”
- Nature posted a video by members of the ENCODE team explaining what their published results mean to human genetics. ENCODE Lead Coordinator Ewan Birney describes the hundreds of terabytes of raw data generated in the 5-year project involving hundreds of people. “There are probably things that we have no idea what they’re doing and yet they’re doing something important,” he says, hinting at potentially more than 80% function. “It’s very hard to get over the density of information,” he said. Genes can no longer be considered discreet sections of code. The data looks more like a jungle. There are “places in the genome we thought were silent and they’re teeming with life,” he said.
- A profile of Ewan Birney was written by Elisabeth Pennisi in the current view of Science (Sept 7, 337:6099, page 1167–1169, doi:10.1126/science.337.6099.1159). Birney is “a self-taught programmer turned bioinformatician” who brought hundreds of people together and worked very hard to bring knowledge of the human genome to this point.
- “Human Genome Is Much More than Just Genes,” Elizabeth Pennisi wrote for Science NOW. The project provided a kind of “Google Maps” for the genome, allowing studies of the epigenome (codes above the genetic code) and regulatory elements that might be implicated in disease.
- “ENCODE Project Writes Eulogy for Junk DNA” is another article by Elizabeth Pennisi in Science Sept 7, pp. 1159–1161. Sample quotes by scientists:
- “I don’t think anyone would have anticipated even close to the amount of sequence that ENCODE has uncovered that looks like it has functional importance,” says John A. Stamatoyannopoulos, an ENCODE researcher at the University of Washington, Seattle.
- These results are going “to change the way a lot of [genomics] concepts are written about and presented in textbooks,” Stamatoyannopoulos predicts.
- “It’s a treasure trove of information,” says Manolis Kellis, a computational biologist at Massachusetts Institute of Technology (MIT) in Cambridge who analyzed data from the project.
- “What we found is how beautifully complex the biology really is,” says Jason Lieb, an ENCODE researcher at the University of North Carolina, Chapel Hill.
- “Regulation is a 3D puzzle that has to be put together,” Gingeras says. “That’s what ENCODE is putting out on the table.”
- Alongside a beautiful artwork of the DNA double helix, New Scientist echoed the theme that “junk DNA” is obsolete. “The reams of ‘junk’ DNA that make up the majority of our genetic code appear to have a purpose after all, according to the results of a global research project.” Switches, for instance, have a purpose: “The switches also appear to be spread out over the genome, with some being located at a distance from the gene they are controlling,” reporter Jessica Hamzelou wrote. “Around 95 per cent of the genome appears to be very close to a switch, suggesting that almost all of our DNA may be doing something important.”
- On Science Daily: “Mapping a World Beyond Genes” commented on the epigenome so central to the ENCODE project: “The term ‘epigenome’ refers to a layer of chemical information on top of the genetic code, which helps determine when and where (and in what types of cells) genes will be active. This layer of information includes a suite of chemical changes that appear across the genetic landscape of every cell, and can differ dramatically between cell types.”
- “Yale Team Finds Order Amidst the Chaos Within the Human Genome,” announces another article on Science Daily. After describing the hierarchical information structure of the epigenome, likening it to management levels in a company (but with less “middle management” bottlenecks), this article looked for evidence for evolution in pseudogenes, calling them ” stretches of fossil DNA, evolutionary remnants of an active biological past.” These pseudogenes, though, are not dead: “However, the Yale team shows many of them are resurrected to produce non-coding RNAs, which scientists now know are crucial to the activation and silencing of protein-coding genes throughout the genome.” Remarkably, one of the Yale team members said this proves evolution is smartly economical: “This is another example of nature not wasting resources, a story we see repeated time and time again throughout the 3 billion letters of our genome.”
- Another article on Science Daily seems to dilute the evolutionary claim, though, claiming that ENCODE is a forward-looking project casting off obsolete evolutionary notions: “Fast Forward for Biomedical Research: Massive DNA Encyclopedia Scraps the Junk.” It includes another quote by Birney: “Our genome is simply alive with switches: millions of places that determine whether a gene is switched on or off.”
- Science Daily also printed a press release from the American Society for Biochemistry and Molecular Biology titled, “Major Advances in Understanding the Regulation and Organization of the Human Genome.” This article stressed how ENCODE is filling the “knowledge gap” that the notion of “junk DNA” explained away.
- “Biochemical Functions for Most of Human Genome Identified: New Map Finds Genetic Regulatory Elements Account for 80 Percent of Our DNA” is the title of another article on Science Daily. This one also mentioned evolution, but only briefly, referring to percentages of genes conserved across mammals. Some of these “newly evolved regulatory regions,” however, work to “encode regulators that activate other genes.”
- In a similar vein, another Science Daily article announced, “Millions of DNA Switches That Power Human Genome’s Operating System Are Discovered.” This article discussed not only the computers the scientists used, but how DNA has its own computer-like operating system.
- “Human Genome Far More Active Than Thought: GENCODE Consortium Discovers Far More Genes Than Previously Thought” announced another article on Science Daily. What is GENCODE? The article explained, “The GENCODE Consortium is part of the ENCODE Project that, today, publishes 30 research papers describing findings from their nearly decade-long effort to describe comprehensively all the active regions of our human genome.” The GENCODE team is looking for more genes and finding them. In addition, they found 11,000 “pseudogenes” and found “There is some emerging evidence that many of these genes, too, might have some biological activity.” This hints that pseudogenes may be elevated from evolutionary junk as more is learned about them.
- Of interest to philosophers of science is whether the ENCODE results will leave the notion of a “gene” intact. Another article on Science Daily is headlined, “In Massive Genome Analysis ENCODE Data Suggests ‘Gene’ Redefinition.” For one thing, the “junk DNA” advocates were wrong: “Far from being padding, many of these RNA messages appeared to be functional.” Even more important. genes are sometimes not distinct loci: “The additional knowledge that parts of one gene or functional RNA can reside within another were surprising, and suggested a picture of the architecture of our genome that was much more complex than previously thought.” Functions for the remaining 20% of DNA left undefined by ENCODE may be found in the differential gene expression within body tissues, because “a large percent of non-protein-coding RNAs are localized within cells in a manner consistent with their having functional roles.” And even though some RNAs are not associated with genes, they are increasingly viewed as something greater: a “giant, complex switchboard, controlling a network of many events in the cell by regulating the processes of replication, transcription and translation.” With these new realizations, one team member commented, “New definitions of a gene are needed.”
- According to an article in Science Daily, “The full ENCODE Consortium data sets can be freely accessed through the ENCODE project portal as well as at the University of California at Santa Cruz genome browser, the National Center for Biotechnology Information, and the European Bioinformatics Institute. Topic threads that run through several different papers can be explored via the ENCODE microsite page at Nature.com/encode.”
- The Wall Street Journal provides a sample of coverage from a media site not devoted to science per se: “‘Junk DNA’ debunked” is the headline. “The discovery ‘is like a huge set of floodlights being switched on’ to illuminate the darkest reaches of the genetic code, said Ewan Birney of the European Bioinformatics Institute in the U.K., lead analysis coordinator for the Encode results.” Stamatoyannopoulos commented, “We created a dictionary of the genome’s programming language.” Noting that humans have about 30 times as much ‘junk DNA’ (regulatory elements, actually) as other other species, the WSJ said, “The unexpected level of activity seen in the genomic hinterlands may also help explain what makes us human.” With 30+ papers on the ENCODE project in print and more coming, “The flood of scientific data is likely to keep researchers busy for a long time.”
In contrast to all the above articles celebrating information and function in non-coding DNA, New Scientist posted a hold-out article advocating, “Don’t junk the ‘junk DNA’ just yet.” Is there still “function” in that vanishing term? “The ENCODE project has revealed that 80 per cent of our genome does something, but doing something is not the same as doing something useful,” the article points out: “there are still very good reasons for thinking that most of our DNA is far from essential.” The statement confuses “essential” with “adaptive” and begs the question whether something useful must be essential. A second hand is useful but not essential or else amputees would never have children. The short article was not specific and did not refer to evolution. “ENCODE is an epic project that will undoubtedly lead to many advances, but it is premature to leap to grand conclusions,” the article warned. “Just as the much anticipated human genome project revealed more than a decade ago, ENCODE tells us we still have an enormous amount to learn from the book of life.”
Intelligent Design advocates are, meanwhile, gloating over the demise of “junk DNA” and pointing to the exceptional complexity ENCODE has revealed. Casey Luskin at Evolution News & Views whipped out “Junk No More: ENCODE Project Nature Paper Finds ‘Biochemical Functions for 80% of the Genome’” on the day of Nature’s announcement. Robert Crowther reminded readers of Evolution News & Views that “Jonathan Wells Got It Right In The Myth of Junk DNA,” published by the Discovery Institute. “In 2010 in The Myth of Junk DNA, biologist Jonathan Wells exposed the false claim that ‘junk DNA’ provides decisive evidence for Darwin’s theory,” he said. “Now he has been vindicated by the leading scientific publications in the world.”
Evolutionists are desperately struggling to hang onto their theory in the floodlights revealing layers of complexity far beyond anything Darwin could have conceived. Blobs of protoplasm, ha! How about operating systems, switchboards, and hierarchical management structures? It’s over, Darwinists. You messed up on vestigial organs, the fossil record and now junk DNA. Please step aside and let the science of the information age take care of what the evidence demands.