On the gain of genes and gene function

Michael Behe recently published a review article in the Quarterly Review of Biology entitled Experimental evolution, loss-of-function mutations, and “the first rule of adaptive evolution” (subscription required), which consists largely of a review of laboratory experiments addressing the adaptive response of microorganisms to simple environmental changes. Behe generates a new definition – Functional Coded elemenTs (FCTs), essentially any segment of DNA that has a biological function, and a “rule”, the “first rule of adaptive evolution”, which essentially states that the majority of adaptive changes reflect mutational events are those which impair or eliminate FCT function.

Update: please note the first comment on this article, which outlines in more detail problems with Behe’s “first rule”.

My own view is firstly, that the data Behe relies on come largely from simple laboratory experiments on microbes (mostly bacteria) generally cultured as a monoculture away from other bacterial species and their bacteriophages (viruses), and secondly that the examples given for eukaryotic adaptation (of humans to endemic malaria) are peculiarly interpreted. Jerry Coyne has published several blog articles reflecting on this paper (Behe’s new paper; IDers already distorting Behe’s new paper; Casey Luskin distorts Behe’s paper; An experimental evolutionist replies to Behe), so there’s really no need to revisit it, other than to note the reservations I have.

What’s a bit more interesting is recently published evidence on the evolution of new genes in the fruit fly Drosophila (in fact these papers look as several species of Drosophila rather than just the common lab species Drosophila melanogaster).

In the first, Chen et al (2010) compared the genome sequences of different species of Drosophila. Again, Jerry Coyne’s beaten me to it with a detailed review of the paper (New genes arise quickly), but in essence, the authors investigated the gene differences between the species in the D. willistoni and D. melanogaster lineages, which diverged about 35 million years ago. Their aim was to evaluate how often genes appeared within the D. melanogaster lineage. In Behe’s new terminology, these would be gain-of-FCT. To summarise, Chen et al:

• Identified 566 new genes in the D. melanogaster genome and dated their evolutionary ages through phylogenetic distributions.

• Assayed the effects of loss of function by RNA interference – of 195 ‘young genes’ tested, 59 gave lethal phenotypes. In other words slightly more than 30%.

• The frequency of young genes with essential function is not statistically different from the corresponding frequency of ‘old genes’, 35%.

Coyne notes in his blog article (New genes arise quickly) that

The presence of frequent gene duplications is supported by an independent study:  Emerson et al. (2008) found that in only fifteen lines of D. melanogaster from nature there were several hundred duplicate genes segregating as polymorphisms (that is, some individuals had one copy of a gene, some had two or more).  They estimated that 2% of the genome was tied up in this copy-number variation.  Clearly, there are a lot of duplicate genes variants floating around in nature.

Indeed, some years ago my laboratory identified a case of gene duplication in D. melanogaster that was presumably a recent event, being present in only some lab strains. It’s quite clear that these sorts of observations are widespread across genomes of species in which the genomes of many individuals have been looked at. Copy number variation is widespread among humans.  What is the usual fate of a duplicated gene?  In many cases, the duplicated gene may have lost vital elements required for correct expression (those sequences important for correct spatiotemporal expression patterns).  In such a circumstance it is likely to be non-functional (i.e. a pseudogene).  If the new copy has retained the capacity for expression, it may still acquire sequence changes which cause loss of function (i.e. it will become a pseudogene).  However, two other outcomes are possible: neofunctionalisation and subfunctionalisation.  In the former, one of the duplicate genes acquires a novel function, while in the latter, one of the genes performs a subset of the functions of the original gene.  Several mechanisms can lead to these outcomes.

In a second paper, Ding et al (2010) looked at the origins and function of young duplicated genes in Drosophila, and focusses on the members of the kep1 gene family, with particular reference to the appearance of new functions. In D. melanogaster, kep1 is a pre-mRNA splicing factor, influencing female fertility, eye development, and immune responses to bacterial infection.

The diagram shows the lineages of several Drosophila species (ana = anannasae; ere = erecta; yak = yakuba; sim = simulans; mel = melanogaster).  In these lineages, the points of origins of the members of the kep1 family are shown as horizontal bars.  Not all members of the gene have been named: those gene names in the form CGxxxx are working names allocated during the Drosophila genome project.

Loss of function mutants of each of the four functional additional members of the D. melanogaster kep1 family (CG4021, nsr, CG3927, CG33318) were analysed.  All of these mutant alleles involved deletion of some or all of the genes involved: two were obtained by targeted mutagenesis and two by imprecise excision of the transposable P element.  CR9337 is a pseudogene – a duplicated gene that has lost biological function.

Loss of nsr leads to almost complete male sterility (see Figure 3 for an illustration of the mutant alleles and the severely reduced fertility of nsr mutant males) – a phenotype distinct from that of kep1 mutants.  The authors analyse the biological function of nsr in considerable detail: it turns out to play its important role in male fertility by regulating several Y-linked genes that are known to be required for male fertility.  [In Drosophila, the Y chromosome does not itself specify male-ness as it does in humans: rather the primary sex determination signal is the ratio of X chromosomes to autosome sets.  Thus a fly with a single X chomosome will be male, though sterile because it lacks the Y chromosomal fertility factors.  The Y chromosome is also rather peculiar, both in terms of its gross structure but also in the structure of individual genes.]  Interestingly, loss of kep1 function leads to female, but not male fertility, while loss of CG4021 or CG3927 did not lead to male sterility.

So, do the analyses of nsr sequence and function suggest that it is derived from neofunctionalisation or subfunctionalisation forllowing the original duplication event?  Ding et al suggest their data point to the former, but do not exclude the latter.  In support of neofunctionalisation, they observe that:

• kep1 is under strict purifying selection across the Drosophila lineage studied.
• Comparative sequence analysis of nsr shows strong positive selection
• kep1 expression in the testis could not be detected in D. yakuba, suggesting the ancestral function of kep1 did not involve testis development.

On the other hand, the conclusion that nsr may have arisen by subfunctionalisation is still possible.  For example, kep1 my have lost its male fertility role in the D. yakuba lineage.  In any event, during the evolution of the melanogaster subgroup, nsr has not only arisen through gene duplication, but has been integrated into some pretty important biological processes.

How do these two papers relate to Behe’s proposal?  They do illustrate the extent to which novel gene functions arise during evolution, and that newly duplicated genes can be integrated into fundamental biological processes.  It’s interesting to note that the kind of experimental evolution experiments conducted using microorganisms and as reviewed by Behe are difficult (or at least time consuming)  to perform in eukaryotic laboratory organisms.  It’s clear from these two papers (and many other examples in the literature) that the increasing quantity of genome sequence data, not only of different species but of multiple individuals within species, has provided us with significant insight into the origins and diversification of genes.

References

Chen et al (2010) New Genes in Drosophila Quickly Become Essential. Science 330; 1682-1685. doi:10.1126/science.1196380. [Subscription required]

Ding et al. 2010. A Young Drosophila Duplicate Gene Plays Essential Roles in Spermatogenesis by Regulating Several Y-Linked Male Fertility Genes. PLoS Genetics 6; e1001255. doi:10.1371/journal.pgen.1001255. [Open Access]

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The Institute for Creation Research reveal their scientific illiteracy.

In a recent blog posting (No Fruit Fly Evolution Even after 600 Generations), Institute for Creation Research ‘science’ writer Brian Thomas misinterprets (deliberately or otherwise) two classic experiments in genetics, and one that has been recently published.  The ICR website doesn’t permit commenting, presumably to exclude people popping over to point out errors in their writing.

The first example concerns work conducted by Nobel prizewinners Christiane Nusslein-Volhard and Eric Wieschaus, and published in several peer-reviewed papers in the 1980s (see for example Nature 287, 795-801 (30 October 1980) | doi:10.1038/287795a0). The reason why Nusslein-Volhard and Wieschaus (along with Ed Lewis) won the Nobel Prize for Physiology or Medicine (there is no Nobel Prize for Biology) in 1995 was that they identified many of (if not most of) the genes that underpin the specification of body plan in the embryonic and adult development of the fruit fly Drosophila. The significance, of course, being the high level of conservation between these Drosophila genes and their counterparts in other animals, including humans. Of course the ICR don’t like this, since it correlates pretty well with evolutionary theory.

Now, what is it that Thomas thinks is the key take-home work from the ground-breaking experiments of Nusslein-Volhard and Weischaus?

If evolutionary biologists could document such evolution in action, they could vindicate their worldview and cite real research to support their surreal claims. In 1980, this search for proof led researchers to painstakingly and purposefully mutate each core gene involved in fruit fly development. The now classic work, for which the authors won the Nobel Prize in 1995, was published in Nature. The experiments proved that the mutation of any of these core developmental genes―mutations that would be essential for the fruit fly to evolve into any other creature―merely resulted in dead or deformed fruit flies. This therefore showed that fruit flies could not evolve.

This paragraph illustrates Thomas’ lack of understanding. Nusslein-Volhard and Weischaus clever stratagem was to realise that many of the genes that are required for correct embryonic development would be recessive lethal mutations, because loss of function would result in severely abnormal development. Nusslein-Volhard and Weischaus therefore generated collections of Drosophila strains bearing lethal mutations that cause death in the embryonic stages. They then examined embryos from each of these strains for embryos with evidence of abnormal development. Typical examples would include abnormal segmentation, embryos with incorrect specification of anterior and posterior and so forth.

So a real examination of Thomas‘ claims do not hold water: Nusslein-Volhard and Weischaus did not “painstakingly and purposefully mutate each core gene involved in fruit fly development”, they generated a large number of mutants and looked for those that specifically affected embryonic development. Also Thomas’ claim that the mutants “merely resulted in dead or deformed fruit flies” is also wrong: the whole point of the experiment was to identify mutations that yield abnormal embryos. Indeed the experiments were not aimed at demonstrating that fruit flies could evolve. On the other hand, the similarity between the Drosophila genes that Nusslein-Volhard and Weischaus identified and the counterparts found in all segmented animals provides very good support for the evolution of all these taxa.

On the subject of Richard Lenski’s E. coli experiments, I refer Brian Thomas to P. Z. Myers’ Pharyngula blog, which discussed the paper (Historical contingency in the evolution of E. coli), and dealt with the creationist misunderstanding (wilful or otherwise): creationists across the internet have spent a good deal of time trying to discredit Lenski’s work and failing.

Thomas also reveals his poor grasp of biology in his discussion of a recent paper in Nature (Burke et al (2010) Genome-wide analysis of a long-term evolution experiment with Drosophila. Nature 467, 587–590 doi:10.1038/nature09352), which describes a lengthy experiment in which a population of Drosophila was selected for rapid development over about 600 generations. Normal Drosophila can develop from egg to adult in about 10 days at 25^oC: this experiment yielded flies that developed about 20% faster. As an experimental biologist (rather than an armchair creationist) might expect, a number of correlated phenotypes also evolved, including shorter lifespan, smaller body size and reduced starvation resistance.

To simplify the findings of the paper, detailed and extensive DNA sequencing revealed that in comparison between selected and unselected populations:

• One sequence variant every 175 bases

• Over 37000 of these variants potentially impact on gene function

• 662 variants in 506 genes are predicted to have a significant effect on function

• The majority of the genes are known or predicted to play a roles in development

I wonder whether the ICR don’t have a subscription to Nature or that they are unwilling to pay for the pdf – it certainly seems as though Thomas’ reading is limited to the abstract. Thomas’ conclusion from his ‘reading’ of the paper is:

The study’s authors wrote, “In our sexual populations, adaptation is not associated with ‘classic’ sweeps whereby newly arising, unconditionally advantageous mutations become fixed.”

They suggested that perhaps there has not been enough time for the relevant mutations to have become fixed. They also suggested an alternative—that natural selection could be acting on already existing variations. But this is not evolution, and it is actually what creation studies have been demonstrating for many years.

The abstract, which is freely available on the Nature website, reads (in part):

[...] in our sexual populations, adaptation is not associated with ‘classic’ sweeps whereby newly arising, unconditionally advantageous mutations become fixed. More parsimonious explanations include ‘incomplete’ sweep models, in which mutations have not had enough time to fix, and ‘soft’ sweep models, in which selection acts on pre-existing, common genetic variants. We conclude that, at least for life history characters such as development time, unconditionally advantageous alleles rarely arise, are associated with small net fitness gains or cannot fix because selection coefficients change over time.

Actually, may take on this paper (and bear in mind that this population genetics is not my field in Drosophila genetics) is that it has demonstrated the genetic consequences of long term artificial selection for a characteristic which probably leads to pretty disadvantageous outcomes for the animal (reduced lifespan, reduced body weight, reduced starvation resistance), and the point the authors make is that the dynamics of genetic diversity under selection is rather more complex than seen is simpler, asexually reproducing organisms. None of this is particularly contentious, and it in no way represents evidence against evolution.

Except in the eyes of the ICR and its staff writers.

H/T: Psiloiordinary (BCSE)

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The Theos think tank invites entries in a competition to summarise The Origin of Species in a tweet:  Darwin’s Origin of Species evolves to a Tweet.  Whether this turns out to be a good thing is probably rather moot!  Theos say:

Fans of Britain’s most famous scientist are being asked to encapsulate the over 600-page seminal work into 140-character tweets on the popular Twitter website.  The competition comes ahead of tomorrow’s (Tuesday) 150th anniversary of the publication of the book, which sets out Darwin’s theory of evolution.

The Origins twittercomp was actually announced on 20th November, but it didn’t cross my radar till just now.  The Theos article also punts their recent report, being the fourth and final report in the Theos Rescuing Darwin series: Doubting Darwin.  It’s succeeded, I just downloaded it and will take a look.
One final comment: how does one enter the competition?

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The Skeptic Society‘s e-newsletter, e-Skeptic, has made an interesting document available for temporary download: How to Debate a Creationist. Looks to be a very useful document.

Hat tip: British Centre for Science Education

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One of the great stories about American cinema is that in credits for the 1929 Pickford-Fairbanks film version of “The Taming of the Shrew” was the line “With Additional Dialog by Sam Taylor”. Most unfortunately, it would seem that this just isn’t so, and it’s an urban legend. So, why is this turning up in my atheism blog?

The (unfortunately) well-known creationist Ray Comfort, who runs a number of websites aimed at discrediting evolution and/or atheism has re-published Darwin’s “On the Origin of Species”. Rather cheekily, this seems to be credited at amazon.co.uk as being written by Charles Darwin and Ray Comfort (it has to be said, in the interests of truth, that the cover image provided by Amazon.co.uk – pictured right – makes no mention of Ray banana man Comfort). Furthermore, judging from the reviews of this edition at amazon.co.uk, the initial listing conflated reviews of this version (bowdlerised not only by inclusion of Comfort’s crass creationist introduction but also by excision of key material) mixed with reviews of more acceptable editions. It would seem that the resounding raspberry of the seven reviews to date are now specifically associated with this version.

There has been an ongoing debate over this edition of Origins over at the US News website, beginning with NCSE Director Eugenie Scott’s piece (How Creationist ‘Origin’ Distorts Darwin) and Comfort’s attempts at justification. Scott pointed out Comfort’s evisceration of Origins:

Unfortunately, it will be hard to thoroughly read the version that Comfort will be distributing on college campuses in November. The copy his publisher sent me is missing no fewer than four crucial chapters, as well as Darwin’s introduction. Two of the omitted chapters, Chapters 11 and 12, showcase biogeography, some of Darwin’s strongest evidence for evolution. Which is a better explanation for the distribution of plants and animals around the planet: common ancestry or special creation? Which better explains why island species are more similar to species on the mainland closest to them, rather than to more distant species that share a similar environment? The answer clearly is common ancestry. Today, scientists continue to develop the science of biogeography, confirming, refining, and extending Darwin’s conclusions.

Likewise missing from Comfort’s bowdlerized version of the Origin is Chapter 13, where Darwin explained how evolution makes sense of classification, morphology, and embryology. To take a simple example, why do all land vertebrates (amphibians, mammals, and reptiles and birds) have four limbs? Not because four limbs are necessarily a superior design for land locomotion: insects have six, arachnids have eight, and millipedes have, well, lots. It’s because all land vertebrates descended with modification from a four-legged (“tetrapod”) ancestor. Since Darwin’s era, scientists have repeatedly confirmed that the more recently two species have shared a common ancestor, the more similar are their anatomy, their biochemistry, their embryology, and their genetics.

The blogosphere has been full of protests about this edition of Origins – I can’t list all articles, but here are two links to PZ Myers’ Pharyngula: Ray Comfort is a parasite (in relation to which, I note that Comfort’s bowdlerised version no longer tops the list in the search results at amazon.com) and Ray Comfort Replies to Eugenie Scott.

(This post was composed offline and submitted via Bilbo Blogger, now sadly renamed Blogilo. Let’s see how well it works!)

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Discover magazine ran a competition for videos which explained evolution in two minutes (The Winner: Evolution in Two Minutes, or less).  PZ Myers (Pharyngula) appears to have been involved in judging the entries (and you can see him in a video there).  The video below isn’t the winner, but it’s the “Peoples’ Choice”, and the one I like.

Evolution on 120 seconds

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I’ve always thought of zoological gardens with larger establishments in mind – such as the Zoological Society of London’s Regents Park Zoo, or the Edinburgh Zoo, and expected these respectable zoos to act as sources of information about animals from around the world.  Of course there’s plenty of scope for rather more specialised zoos, such as those focussing on conservation.  Unfortunately it would seem there are also zoos with the purpose of misinforming the public.

I imagine the name of the Noah’s Ark zoo in North Somerset is something of a giveaway.  It is a small, privately run zoo which clearly espouses a creationist agenda.  Now the British Humanist Association has pointed this out, and it’s hit the media (Bristol Evening Post – Zoo attacked over Creationist beliefs; BBC News – ‘Creationist’ zoo causes dismay).  The Bristol Evening Post quotes Noah’s Ark research assistant Jon Woodwood as saying:

“To say that we are not upfront with our beliefs is unfounded – the name Noah’s Ark is the first indicator.  Our education policy is purely based around the National Curriculum.  We are offering our visitors the chance to look at the evolution/creation debate. As it is a free country, that is within our right. Contrary to a small minority of people’s claims we do not teach false science.  This is clearly shown within the zoo, with one exhibition talking about Darwin and another offering another point of view.

“We are slightly different from popular Creationism and hold a view that the natural world around us is the product of both God and evolution.  Although technically Creationists, we do not hold the stereotypical Creationist views that the world was created 6,000 years ago and there is no evolution.”

Woodward went o to say that the number of complaints on this subject was very small (10 in 120,000 visitors).  Interestingly, BBC page has an image of one of the signs at the zoo, with the text:

It also shows how three great people groups are descended from the sons of Noah: Shem, Ham and Japheth.
[and in smaller font] (who could have become the three races of humans alive today, that we knwo as the Semitic, the Negroid/Mongoloid and the White Caucasian).

Rather worryingly, the Evening News article quotes a Visit England spokesman as saying “Noah’s Ark adheres to the Visitor Attraction Quality Assurance Service criteria. We do not comment on the content of any attraction.”  It does seem to me that the content of an “attraction” is rather important when assessing its quality!

Looking through the educational links from the Noah’s Ark website takes you through a variety of relatively inoffensive topics, occasionally written in a curious style.  Unfortunately, a prominent item on the main tool bar menu is Creation Research.

Here it’s clear the owners of the zoo have their own take on creationism in which the fossil record reflects recolonisation after the Noachian flood.  The page goes on to spread the usual creationist canards…

Palaeontologists have struggled for more than a century to find transitional fossils to confirm the predictions of Darwinism. But, with some exceptions, these have not been found. See Darwinist steps of faith – the many missing links (at the time of writing this blog article, this link was to a page still to be written). Radioisotope dating has been used to show that the fossil record unfolded over billions of years. We suggest that while the method is not itself invalid, the dates produced by it are not supported by the primary evidence of the rocks and fossils themselves. See An Earth billions of years old?

There appears to be a mixed message here.  On the one hand, brief outlines of educational material, backed with larger expositions of an unfounded creationist agenda.  Noah’s Ark seems to push an identity as an attraction that can offer an range of educational activity, but on the evidence of its website, this seems to be a cover for a significant creationist agenda.  And I don’t think this can be purely based on the National Curriculum – after all people presumably don’t go to a zoo for RE!

I have to conclude that the BHA has a point, and that Visit England really ought to reflect on the meaning of “quality”.

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So here’s an interesting story (Creationist exams comparable to international A-levels, says Naric).  I’ve never heard of Naric before – it’s the National Recognition Information Centre, and is tasked with advising universities and employers on the rigour of lesser-known qualifications. Unfortunately it’s pronounced on the International Certificate of Christian Education (ICCE). One might have had alarm bells ringing at the mere title of that “qualification”, and really those alarm bells would be justified.

Naric has ruled that the ICCE is comparable to courses such as international A-levels. Unfortunately, one of the ICCE textbooks says:

“Have you heard of the ‘Loch Ness Monster’ in Scotland? ‘Nessie,’ for short has been recorded on sonar from a small submarine, described by eyewitnesses, and photographed by others. Nessie appears to be a plesiosaur.

“Could a fish have developed into a dinosaur? As astonishing as it may seem, many evolutionists theorize that fish evolved into amphibians and amphibians into reptiles. This gradual change from fish to reptiles has no scientific basis. No transitional fossils have been or ever will be discovered because God created each type of fish, amphibian, and reptile as separate, unique animals. Any similarities that exist among them are due to the fact that one Master Craftsmen fashioned them all.”

To anyone with a modicum of understanding, this is just appalling, and the fact that in 2009 we have schools teaching this rubbish to children is nothing short of scandalous. Oh, and did you know that apartheid was helpful to communities in South Africa because it “made it possible for each group to maintain and pass on their culture and heritage to their children”?

Appalling. And to think that there are 50 christian schools peddling this stuff.

Naric is funded by the Department for Business, Innovation and Skills (Mandelson’s empire, and the Department that oversees Universities) – but a Naric spokesman is quoted in the Guardian as saying that its remit did not cover the curriculum’s content. Which makes me wonder what sort of advice regarding the rigour of qualifications they are capable of providing.

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There’s a nice audioslideshow at the BBC News site: Audio slideshow: Darwin’s Endless Forms.  It features images in an exhibition at the Fitzwilliam Museum in Cambridge.  If. like me, you’re unlikely to be able to visit the exhibition (which is open 16 June – 4 October 2009) , it’s an interesting narrated slideshow.

The Fitzwilliam Museum website’s worth visiting too.

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I switched on the radio this morning and fortuitously caught this morning’s edition of Science in Action.  The first item in the programme was Ida, the unlikely name given to Darwinius masillae, possibly the most over-hyped fossil in recent years (check my comments to my previous blog article for links to the growing controversy).

In the radio show, one of the authors of the paper speaks briefly, but is then followed by a series of contributors who basically say – while this is a spectacularly well-reserved fossil, no this isn’t quite as important as the media puffery would make out.  Steve Jones takes exception to the use of “missing link”.

You can listen to the show through BBC iPlayer (well, you can in the UK, and maybe elsewhere, given that this is the World Service) for the next week: Science in Action, Friday 22nd May (presumably I caught a repeat broadcast)..

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