Tag: genome

Coelacanth genome sequenced

April 19, 2013 • 4:08 pm

by Greg Mayer

Coelacanths are one of the three surviving groups of sarcopterygian (lobe-finned) fishes, and along with lungfish, one of the two groups that have remained fish in the vernacular sense (we tetrapods, the third surviving group, have of course become legged). The coelacanths also have a tremendous back story: known in the fossil record from the Devonian (over 350 mya) till the end of the Mesozoic Era (about 65 mya) but not afterward, it came as a great shock when one popped up in South Africa in 1938.

Latimeria chalumnae, the coelacanth (model)
Latimeria chalumnae, the coelacanth (model). Notice lobed fins.

Marjorie Courtenay-Latimer, curator of the local museum, got it at the fishing wharf in East London, Cape Province, where a fishing captain had put it aside for her as an unusual specimen. The discovery of a living specimen of a fish long thought extinct, and one related to tetrapods to boot, was a worldwide sensation. Others eventually turned up at various points in the western Indian Ocean, and in 1998 a population was discovered in Indonesia at the opposite end of the Indian Ocean.

Yesterday, a group led by Chris Amemiya (and including friend-of-this-site Neil Shubin) published the genome sequence of the coelacanth in the journal Nature. It is open access, and remarkably long and detailed given Nature‘s cramped editorial style. To me, two things stand out after a quick look. First, the coelacanth is the next closest relative to the tetrapods, after the lungfish. This is what was expected, but the paper provides much stronger support for this, using a  large data set (251 judiciously chosen genes). Note that, in an especially nice touch, Homo sapiens is represented in the figure by Miss Courtenay-Latimer herself.

Phylogenetic tree using coelacanth genomic data (Fig. 1 from Amemiya etal. 2013).
Phylogenetic tree using coelacanth genomic data (Fig. 1 from Amemiya etal. 2013).

Second, although, slightly more distantly related genealogically to tetrapods than lungfish, the slowly evolving coelacanths provide better comparisons for inferring events in early tetrapod genomic evolution than do the highly genomically derived lungfish. As Ammemiya et al. put it,

The vertebrate land transition is one of the most important steps in our evolutionary history. We conclude that the closest living fish to the tetrapod ancestor is the lungfish, not the coelacanth. However, the coelacanth is critical to our understanding of this transition, as the lungfish have intractable genome sizes (estimated at 50–100 Gb)47. Here we have examined vertebrate adaptation to land through coelacanth whole-genome analysis, and have shown the potential of focused analysis of specific gene families involved in this process. Further study of these changes between tetrapods and the coelacanth may provide important insights into how a complex organism like a vertebrate can markedly change its way of life.

This is a bit reminiscent to the situation in studies of vertebrate origins: it now seems clear that sea squirts (urochordates) are closer genealogically to vertebrates than lancelets (cephalochordates), yet lancelets provide better comparative material for investigating early vertebrate evolution than do the highly derived sea squirts.

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Amemiya, C., et al. 2013. The African coelacanth genome provides insights into tetrapod evolution. Nature 496:311-316. (pdf)

Holland, P. 2006 My sister is a sea squirt? Heredity 96:424–425. (pdf)

Neanderthals are us?

May 15, 2011 • 9:03 pm

by Greg Mayer

At least since Socrates explored the meaning of the Greek maxim “Know thyself”, and Alexander Pope added that “the proper study of Mankind is Man”, we have been interested in knowledge about ourselves. But who are we? A paper in press in the Proceedings of the National Academy of Sciences by Ron Pinhasi and colleagues raises this issue with regard to Neanderthals, an issue which Jerry considered a while back: are they us?

In several senses, they obviously are us: fellow mammals, fellow primates, fellow hominids, and fellow members of the genus Homo, and thus men in the generic sense (in both the vernacular and technical senses of generic). But are they members of the same species as us, Homo sapiens? Or members of a distinct species, Homo neanderthalensis?

Life reconstruction of a Neanderthal by John Gurche at the USNM.

The question of whether they are a different species from us is the question of whether or not we could interbreed with each other. And not just mate– but successfully produce fertile offspring. For most of the time since the first reported Neanderthal in 1856, reproductive compatibility could only be inferred based on morphological data, and opinions varied as to whether Neanderthals were a subspecies of H. sapiens or a separate species. The great Finnish paleontologist Bjorn Kurten proposed in his novel, Dance of the Tiger, that Neanderthals and modern H. sapiens could mate and produce offspring, but that the offspring, while showing somatic luxuriance (they were really smart and strong), were completely sterile (a form of post-mating reproductive isolation). Published in 1980 before there was any genetic evidence, a novel, rather than a scientific paper, was probably the right venue for Kurten’s reasoned but entirely speculative proposal.

Early genetic data from mitochondrial DNA indicated that Neanderthal mitochondria were well outside the variability of modern populations, supporting the ideas of those (such as Kurten) who supposed that Neanderthals were a separate species. More recently obtained nuclear DNA sequences, however, showed that 1-4% of the genome of modern Eurasians was derived from Neanderthals (modern Africans lack this admixture of Neanderthal DNA). Thus there was enough successful interbreeding to leave a noticeable signature in modern genomes. Even more recently, a previously unknown fossil Asian population called Denisovans, related to but distinct from Neanderthals, has been shown to have contributed about 5% of the genome of modern Melanesians. Thus, measurable interbreeding occurred between anatomically modern humans and more archaic Eurasian populations as the former spread out of Africa across the remainder of the Old World.

The paper by Pinhasi et al. revises the dating of Neanderthal fossils from the Caucasus, finding them to be older than previously thought (about 40,000 years BP). The authors also suggest that other younger dates are unreliable, and that it is unlikely that anatomically modern humans and Neanderthals coexisted for any substantial length of time. If they are correct, then the Neanderthal (and Denisovan) contribution to modern genomes speaks even more strongly of conspecficity, as the gene flow had to occur over shorter periods of time. There are, regrettably, quite a few historical instances where two peoples (both of course undoubted anatomically modern H. sapiens) met, and one quickly disappeared, with relatively little measurable gene flow having occurred, so the rapid demise of Neanderthals in the face of anatomically modern humans is no bar to their having been the same species. I would interpret the genetic evidence so far as indicating that the Neanderthals, indeed, are us.

In addition to the references below, John Hawks of the University of Wisconsin, Madison, has a fine blog in which he often comments on Neanderthals and other paleoanthropological topics. His take on the Pinhasi et al. paper, which deals more with the dating issues, is here; his view on the species question is here. [JAC: I also discussed the species problem in Neanderthals, reaching the same conclusion as Hawks.]

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Green, R.E. et al. 2010. A draft sequence of the Neandertal genome. Science 328:710-722.

Green, R.E., et al. 2008. A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell 134:416-426.

Kurten, B. 1980. Dance of the Tiger. Reissued by University of California Press, Berkeley, 1993.

Pinhasi, R., T.F.G. Highamb, L.V. Golovanovac, and V.B. Doronichev. 2011 Revised age of late Neanderthal occupation and the end of the Middle Paleolithic in the northern Caucasus. Proceedings of the National Academy of Sciences in press.

Reich, D., et al. 2010. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468:1053-1060.

US government opposes gene patenting

November 9, 2010 • 12:14 am

by Greg Mayer

In a move that got lost in the run up to the recent US elections, the Federal government has reversed its longstanding policy that genes are patentable. Released the Friday before the elections, and covered by the New York Times the following day, with a follow up article the day before the election, the Justice Department’s brief in the case argued that gene sequences unmodified by man are products of nature, and thus ineligible to be patented; and that isolating the sequence doesn’t change its status. Here’s a summary of the argument:

The district court [which invalidated two gene patents] correctly held, however, that genomic DNA that has merely been isolated from the human body, without further alteration or manipulation, is not patent-eligible. Unlike the genetically engineered microorganism in Chakrabarty [an earlier decision, allowing the patenting of genetically modified organisms], the unique chain of chemical base pairs that induces a human cell to express a BRCA protein is not a “human-made invention.” Nor is the fact that particular natural mutations in that unique chain increase a woman’s chance of contracting breast or ovarian cancer. Indeed, the relationship between a naturally occurring nucleotide sequence and the molecule it expresses in a human cell — that is, the relationship between genotype and phenotype — is simply a law of nature. The chemical structure of  native human genes is a product of nature, and it is no less a product of nature when that structure is “isolated” from its natural environment than are cotton fibers that have been separated from cotton seeds or coal that has been extracted from the earth.

The friend of the court brief was filed in an appeal of a case brought by a group of scientific and medical societies and individuals against Myriad Genetics, which had been granted patents on two genes associated with breast and ovarian cancer. In a surprise ruling last March, US District Court Judge Robert Sweet invalidated the patents (more on the ruling here and here), and the current brief was filed in response to Myriad’s appeal of the adverse ruling. The Feds argue that some aspects of Judge Sweet’s ruling erred, but that it’s main conclusion was correct: “…products of nature do not constitute patentable subject matter absent a change that results in a fundamentally new product. … [T]he purification of native DNA does not alter its essential characteristic– its nucleotide sequence– that is defined by nature…” (pp. 107 & 132 of the ruling, full text here).

The Federal position comes as good news to the scientists and medical groups involved, and to anyone who wants the law to make  sense. The notion that a gene is a human invention, rather than a product of nature, is absurd to any biologist (unless perhaps you were granted one of these bogus patents, which may be one of those cases where, as Upton Sinclair put it, it is difficult to get a man to understand something, when his salary depends upon his not understanding it). This is one instance in which the Obama administration has followed up on his promise that “Science and the scientific process must inform and guide decisions of my Administration on a wide range of issues”.

Russell Blackford has noticed the new anti-patent brief, and also had a nice overview of some of the issues at the time of Sweet’s ruling. NPR also noticed the new brief a few days later.

The human genome ten years on (part 2) – it ain’t necessarily so

June 14, 2010 • 11:14 am

by Greg Mayer

In a post a couple of months ago, Matthew took note of the tenth anniversary of the completion of the draft human genome, noting that Nature had published a retrospective.  Matthew rightfully took issue with the dreadful “blueprint” metaphor for the genome, but also concisely noted the meager medical results:

…despite all the hype, the contribution of the genome to human health has been pretty negligible. In other words, from a purely medical point of view, there isn’t much to celebrate.

In yesterday’s New York Times, Nicholas Wade provides a journalistic analysis, and confirms that the results so far are disappointing. Money quote:

…the primary goal of the $3 billion Human Genome Project — to ferret out the genetic roots of common diseases like cancer and Alzheimer’s and then generate treatments — remains largely elusive. Indeed, after 10 years of effort, geneticists are almost back to square one in knowing where to look for the roots of common disease.

This does not come as much of a surprise when you realize that most diseases are not genetically caused (in any straightforward reading of the word caused); that even when there is a genetic basis, the genetics are apt to be complex; and that even when simple, identification of a gene does not lead readily to a cure. These issues were raised most presciently by Dick Lewontin, especially in an essay-review (subscription required) he wrote for The New York Review of Books in 1992. Dick decried scientists’ selling the genome project to governments on the basis of its health benefits, while in fact the project would primarily advance disciplinary (and, in some cases, financial) interests. Endorsing Dick’s genetic arguments, I wrote the following in 2000, at the time of the announcement by Bill Clinton and Tony Blair:

Few diseases are caused by a “gene.” Most diseases, in fact, are caused by the invasion of the body by another organism (bacteria, viruses, protozoa). Our susceptibility and resistance to disease may often have a genetic basis, but these too are usually the result of multiple genes in interaction with the environment. Even when a disease does have a singular genetic cause, finding the gene does not necessarily lead easily to treatment or prevention (e.g. cystic fibrosis).

Last year, over at Mermaid’s Tale (in a post I noted here at WEIT), Ken Weiss put it succinctly (he also discusses Wade’s new NYT article here):

…most common diseases have little to do with genetic variation in any sensible way.

The genome project has provided much useful scientific information. As Wade notes, “For biologists, the genome has yielded one insightful surprise after another.” But that’s not why the project was done. Bill Clinton said it would lead to treatments for “most, if not all, human diseases”; Francis Collins said we’d have genetic diagnosis of diseases within ten years. The genome project’s architects oversold it’s medical (not to mention philosophical) benefits, and now scientists (or at least genome scientists) will lose credibility because of it. Harold Varmus is quoted by Wade as saying “Genomics is a way to do science, not medicine.” If only that had been said louder, and earlier, and by more people.

[PZ and some others are taking Wade to task for saying “humans… [are] higher on the evolutionary scale”. While this is an inopportune use of the scala naturae, it’s part of one paragraph (which does make the interesting point that genome size, as measured by number of protein coding genes, does not vary very widely among metazoans), and does not detract at all from the main thrust of the article.]