FOXP2 is really recent, it really did introgress (if it's not contamination)

That's the thrust of a technical comment by Graham Coop and colleagues, now online in Molecular Biology and Evolution. The letter refers to the extraction of FOXP2 from two Neandertal specimens from El SidrĂ³n, by Johannes Krause and colleagues, reported last year (I wrote about the paper here).

First, the bad news. The current letter raises the prospect of contamination. Notably, the controls applied by Krause et al. (2007) may be relatively weak evidence against contamination, because of polymorphism within large human comparative samples. The tests rely on the assumption that there is little DNA from living humans in the samples. But if we cannot distinguish Neandertal from human DNA with great accuracy, then we will be mistaken some proportion of the time. Krause et al.'s test, based on derived human alleles absent from the Neandertal genome draft, can still go wrong if the human contaminants happen to have all the ancestral (non-derived) human alleles.

Well, that seems to be the story these days with Neandertal DNA extraction. No test of contamination is good enough. (And remember, that every "test" of contamination is really a procedure for excluding the hypothesis that ancient sequences are identical to recent ones.)

Now, the more interesting news. Coop and colleagues verify that the selective sweep affecting human FOXP2 was indeed recent -- they estimate 42,000 years ago:

To demonstrate this, we estimated the time of the most recent common ancestor (tMRCA) of the selected haplotype (see Figure 1), using an approach sometimes called phylogenetic dating (Thomson et al. 2000; Hudson 2007). This method does not make assumptions about demography and selection, but only requires that the mutations in the intron be neutral or nearly neutral. Taking this approach, we obtained a mean tMRCA of 42 Kya (see SOM for details). While there is considerable uncertainty associated with this estimate, it is surprisingly recent if selection took place over 300 Kya (see SOM). In other words, the selective scenario proposed by the authors cannot account readily for patterns of variation in modern humans. Given that we have no power to detect a beneficial substitution that occurred over 250 Kya, (cf. Sabeti et al. 2006) yet we see a footprint of positive selection at FOXP2, the conclusion of a recent selective sweep at FOXP2 is not surprising (Coop et al. 2008:3-4).

FOXP2 is in one of the ENCODE regions, so its variation is pretty well known. This is not a problematic case: it has a very limited amount of variation around it, and has a strong excess of rare alleles, both signs of a recent sweep.

Coop and colleagues suggest that the beneficial human allele spread into Neandertals (or vice versa) by low levels of gene flow coupled with its selective advantage -- in other words, introgression.

They do allow for an alternative -- perhaps the two amino-acid-coding mutations were not the target of selection, but instead some linked locus. This would not erase the necessity of gene flow from Neandertals, but would question whether this gene flow had involved the FOXP2-language scenario, since it might be some linked gene unrelated to language.

(CORRECTION (2008/04/18): If selection were on a linked site, then Neandertals might share the human-derived amino acids as a result of ancient shared ancestry with humans, while the linked selected sweep might be absent in Neandertals, not necessitating any gene flow.)

I doubt this hypothesis of a linked sweep, since the two sites with human-derived substitutions are otherwise very strongly conserved among mammals. This looks like a credible target for recent selection. But the hypothesis of selection on a linked site cannot presently be tested.

So that's the story. It seems very likely that Neandertals got the language gene from us, or us from them, long after many other genes in the two populations diverged. I write "many" rather than "most" because we haven't really been able to assess the proportion of derived alleles shared by humans and Neandertals. The completion of the draft sequence may help, but I'm afraid that the specter of contamination is going to keep on being raised whenever a part of the Neandertal draft genome looks humanlike.

(via Dienekes)

References:

Coop G, Bullaughey K, Luca F, Przeworski M. 2008. The timing of selection at the human FOXP2 gene. Mol Biol Evol (in press) doi:10.1093/molbev/msn091