On the gain of genes and gene function

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.


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]

C4ID hits back against Ekklesia’s take on ID creationism

Alastair Noble, the Director of the Centre for Intelligent Design, has responded to an article at the Ekklesia website, on behalf of C4ID (Intelligent Design is an explanation not an apolgetic – a response to Ekklesia). Noble doesn’t supply a link to the Ekklesia article, so here it is – ‘Intelligent Design’ is a flawed apologetic.

Dr Noble is a man who cannot (or will not) grasp an understanding of biological systems. I add the possibility “will not” because I suspect that his willingness to accept a natural explanation for the diversity of life around us is in large part informed by his religious beliefs. Indeed, it comes as something of a surprise that he emphasises that Intelligent design creationism

[…] is not a religious apologetic but a scientific explanation of the observed data.

In actual fact, and despite his protestations to the contrary, Intelligent Design creationism is not a scientific explanation. It is untestable and makes no predictions. Intelligent Design creationism was invented by the Discovery Institute with the explicit purpose of inveigling teaching of creationism into US schools, where it is prohibited by the constitution. Is Dr Noble really unaware of this?

I have worked my way through the document ‘An Introduction to Intelligent Design’ (my comments can be read here), which was prepared by Dr Noble and his colleagues at C4ID. Noble continues:

The information in living systems is real and raises, to an enquiring scientific mind, the question of its origin.  To make a valid inference about this we need to offer an explanation which is known to apply elsewhere and to operate in the way we propose.

In actual fact the scientific explanations of the origins and evolution of biological information are comprehensive and do explain its diversity. Intelligent Design makes no explanation of the diversity, unless a designer/creator did it. We may not yet know (and may never know) the chemical origins of complex biomolecules, but stooping to “I don’t know, so a supernatural entity must have been responsible” is rather unsatisfactory, and the kind of explanation nomadic goat herders in the bronze age might have come up with, without the benefits of the scientific method.

Well it’s not hard to see what it is.  The only known source of specified functional information is intelligent mind and to infer that the information in living systems has a similar source is entirely consistent with scientific deductions.  To propose the alternative that this all somehow self-assembled, which curiously almost everybody accepts without question, is contrary to all human experience and reason.  It is about as unscientific as you can be.

If this is not an argument from ignorance, I don’t know what is.

Dr Noble seems to think that the ‘establishment’ finds Intelligent Design creationism unacceptable because it departs from a ‘philosophy of materialism’…

I think what is really unacceptable to the establishment about ID is that it departs from the philosophy of materialism which now dominates the pursuit of science.  This philosophy says, essentially, that only physical or material processes can be considered as valid explanations.  Any other explanation, such as an intelligent cause of the universe, must be ruled out before you begin to assess the evidence.  ID, on the other hand, prefers to go where the evidence leads.

If, in the matter of origins, science wishes to cripple itself with a commitment to rule out, by definition, any non-material explanation for the universe such as intelligent causation, it might be better to do the honourable thing and leave the field because its tools are clearly inadequate to the task of assessing the actual evidence.  But there is no need for science to do that if it is prepared to go where the evidence leads.

And I think there we have it. This paragraph reveals Intelligent Design creationism for what it really is. Dr Noble advocates a non-material explanation for the universe. If he is indeed supporting ‘intelligent causation’, who or what is he proposing as the entity that performed this ‘intelligent causation’? If it’s not his particular deity, it’s remarkably close to the sort of power he attributes to his god. In my more mischievous moments, think that maybe this is some kind of super-deity, that created the god Noble worships?

Please Dr Noble, what is the evidence for a Designer/Creator, other than you cannot understand the science (or that you are blinkered by your religious beliefs)? Oh, and while we’re at it, please could you suggest what designed the Designer?

Noble concludes with a section entitled ‘Debate the Controversy’. Please. Intelligent and educated people realise there is no controversy. It is entirely manufactured by individuals with a religious agenda specifically because they don’t like the potential impact that evolutionary biology might have on their belief system.

So are we up for dialogue?  Of course we are.  That’s why the Centre for Intelligent Design (C4ID) is here.  If ID is soon to be debunked, as Bob Carling suggests, let’s have some credible scientific arguments and not the tired reiteration of neo-Darwinian speculation.

On the contrary, biology provides the best explanations of biological diversity, if anything the C4ID website is a tired reiteration of creationist bunkum masquerading as science.

C4ID and Behe’s tour

Michael Behe has a paper forthcoming in the December Quarterly Review of Biology, entitled Experimental Evolution, Loss-of-Function Mutations, and “The First Rule of Adaptive Evolution”.  It may well be interesting to find out what Behe has to say on mutations.

As one might expect, the biblical literalists at C4ID (who bizarrely promote ID creationism) are gearing up to make the most of it.  Elsewhere in that page, the C4ID crew enthuse about Behe’s reception during his tour, and list the main points he expounded as:

  • Design is not mystical. It is deduced from the physical structure of a system
  • Everyone agrees aspects of biology appear designed
  • There are structural obstacles to Darwinian evolution
  • Grand Darwinian claims rest on undisciplined imagination
  • Bottom line: Strong evidence for design, little evidence for Darwinism

Not much new there, though what the ‘structural obstacles to Darwinian evolution’ might be escape me!  And to claim that ‘Grand Darwinian claims rest on undisciplined imagination’ when one’s own views are based on religious texts is nothing short of bizarre.  C4ID go on to claim:

No academic paper was presented or question asked of Prof Michael Behe that in any way created difficulty except perhaps the lack of time to go into the detail he would have liked to.

The reports of Behe’s tour indicate that serious questioning was hampered by the way questions were submitted.

Significantly, if Intelligent Design isn’t science, then why did opponents attempt to undermine it by citing scientific papers, albeit ones that were largely irrelevant?

The point C4ID make is risible.  To demonstrate the unscientific nature of Intelligent Design creationism, the citation of scientific papers is rather important.  I would challenge C4ID to identify which papers they were, and why they were irrelevant.

Apparently more events will be organised. Oh good.

Goodwill to all…

Season’s greetings to the victimised former Archbishop

The Rev Dr Peter Hearty of the excellent ‘Platitude of the Day‘ website is clearly concerned that former Archbish Carey is rather upset at the (supposed) continued victimisation of christians in the UK*.  He thinks we should send Christmas cards to the poor old soul.

It’s been suggested that Lord Carey deserves a response to his Not Ashamed campaign. He’s obviously feeling a bit down, what with all this Christian persecution that’s going on. I think the idea of sending him a Season’s Greetings card, perhaps with a picture of some jolly penguins or some reindeer on the front, is an excellent way of cheering the old chap up.

Click over to Platitude of the day for more…and don’t be mean!

I think I may well just do the same…and I’m sure Lord Carey, ensconced in the House of Lords with the others who are there merely because they are senior figures of the Church of England will enjoy all those seasonal sentiments and images.

*Of course, not everyone agrees that there is any persecution.  The Bishop of Croydon disagrees (Bishop bashes Christian persecution complex).

Behe’s UK Tour: Westminster Chapel gig

Notes from an Evil Burnee has a report on Behe’s Westminster Chapel talk (Michael Behe: still flogging the flagellum).  Well worth reading – the counclusion is:

It was an interesting but frustrating evening. Given the hype surrounding Behe’s week-long whistle-stop UK lecture tour I had expected something new. But it was the same old nonsense — indeed the same old non-science.