PMC:1271393 / 58468-62118 JSONTXT

{"project":"2_test","denotations":[{"id":"16252244-15385553-2049688","span":{"begin":1315,"end":1319},"obj":"15385553"},{"id":"16252244-15509576-2049689","span":{"begin":1337,"end":1341},"obj":"15509576"},{"id":"16252244-10077682-2049690","span":{"begin":1930,"end":1934},"obj":"10077682"},{"id":"16252244-11014825-2049691","span":{"begin":1950,"end":1954},"obj":"11014825"},{"id":"16252244-12433581-2049692","span":{"begin":1966,"end":1970},"obj":"12433581"},{"id":"16252244-12142358-2049693","span":{"begin":1993,"end":1997},"obj":"12142358"},{"id":"16252244-15531162-2049694","span":{"begin":2018,"end":2022},"obj":"15531162"},{"id":"16252244-15012762-2049695","span":{"begin":2043,"end":2047},"obj":"15012762"},{"id":"16252244-15531162-2049698","span":{"begin":2504,"end":2508},"obj":"15531162"},{"id":"16252244-15012761-2049699","span":{"begin":2518,"end":2522},"obj":"15012761"}],"text":"Two other circumstances may be responsible for the topology and the time depth of the CD209 gene tree: long-standing balancing selection or ancient population structure, with Africa, in both cases, being the arena of such events (i.e., cluster A is restricted to Africa). Several lines of evidence argue against the balancing-selection hypothesis. First, under this selective regime, one would expect that Tajima's D test would also point in this direction by yielding significantly positive values, which is not the case (table 2). Second, such a long-standing balancing selection in Africa would have entailed a number of recombinant haplotypes between clusters A and B, which, again, is not the case, as illustrated by the high LD levels at CD209 (fig. 3). Third, a claim of balancing selection at this locus must imply a functional difference between the two balanced alleles. Indeed, three nonsynonymous mutations, situated in the neck region, separate cluster A and B, and they could correspond to the alleles under selection. But, if the neck region is the target of selection, it is more likely that the balanced alleles would correspond to different numbers of repeats rather than punctual nucleotide variation within each track, as observed for CD209L and suggested by functional studies (Bernhard et al. 2004; Feinberg et al. 2005). Since no variation in the number of repeats was detected between both clusters, we predict that there are no major functional differences between the two lineages. Taken together, maintenance of ancient lineages by balancing selection does not seem to be responsible for the observed haplotype divergence. In this view, the patterns observed are best explained by an ancestral population structure on the African continent. Indeed, several studies have already proposed that African populations must have been more strongly subdivided and isolated than non-African ones (Harris and Hey 1999; Labuda et al. 2000; Excoffier 2002; Goldstein and Chikhi 2002; Harding and McVean 2004; Satta and Takahata 2004; Garrigan et al. 2005a). In particular, a recent study of the Xp21.1 locus presented convincing statistical evidence that supports the hypothesis that our species does not descend from a single, historically panmictic population (Garrigan et al. 2005a). The divergent haplotype pattern observed at the Xp21.1 locus prompted those authors to explain their data under the isolation-and-admixture (IAA) model and/or a metapopulation model (Harding and McVean 2004; Wakeley 2004). Indeed, as observed for CD209, under an IAA model, the two basal branches are expected to be longer than those under a Wright-Fisher model, depending on the length of time subpopulations spent in isolation. The extent to which the IAA model fits the data depends on the number of mutations, referred as to “congruent sites,” occurring in the two basal branches of the genealogy. For Xp21.1, 10 congruent sites over 24 polymorphisms were observed (i.e., ∼42% of the total number of sites). We applied the same approach to CD209 and obtained a very similar percentage of ∼45%, in good accordance with the IAA model. Our observations, together with a number of autosomal diversity studies, show that modern human diversity appears to have kept genetic traces of admixture among archaic hominid populations. However, a number of questions remain unanswered, such as the time when these admixture events occurred (i.e., before or after the appearance of anatomically modern humans), the precise quantitative contribution of ancient genetic material to our modern gene pool, and the geographic provenance of these genetic vestiges."}