X chromosome evidence for ancient human histories

Abstract

Diverse African and non-African samples of the X-linked PDHA1 (pyruvate dehydrogenase E1 alpha subunit) locus revealed a fixed DNA sequence difference between the two sample groups. The age of onset of population subdivision appears to be about 200 thousand years ago. This predates the earliest modern human fossils, suggesting the transformation to modern humans occurred in a subdivided population. The base of the PDHA1 gene tree is relatively ancient, with an estimated age of 1.86 million years, a late Pliocene time associated with early species of Homo. PDHA1 revealed very low variation among non-Africans, but in other respects the data are consistent with reports from other X-linked and autosomal haplotype data sets. Like these other genes, but in conflict with microsatellite and mitochondrial data, PDHA1 does not show evidence of human population expansion.

Figure 1

Polymorphic base positions within humans. Each of the 25 polymorphic positions is listed by its position within the alignment. The base values of the chimpanzee sequences are shown for these positions, and the human haplotypes are shown with respect to the chimpanzee sequences. - indicates the haplotype base was the same as the chimpanzee; ∗ indicates a gap in a sequence relative to the chimpanzee, where a polymorphism fell within an insertion/deletion. The polymorphism at position 2,489 is associated with an amino acid variant (ATG, for methionine, and CTG for leucine). The polymorphism at position 544 is a synonymous variant (GCA and GCG for alanine). All other variants occurred in introns. The haplotype letter designations are the same as those shown in Fig. 2. The B1 haplotype is not included in Fig. 2 because position 3,306 was removed from the genetree analyses of the complete Old World sample (see text). The populations are as follows: B, South African Bantu speakers; S, Senegalese; K, Khoisan from the Angola/Namibia border; P, Pygmy from the Central African Republic; C, China; V, Vietnam; F, France; M, Mongolia. The C, V, and F samples are random subsets of DNAs used in a larger study (45).

Figure 2

The gene tree estimate for PDHA1, with estimated ages of polymorphic mutations. Each mutation is identified by its position in the sequence and by its branch location (as determined by maximum parsimony and maximum likelihood). Mutations that generated new haplotypes are indicated at branch points. For branches with multiple mutations, the order of mutations in time is arbitrary. A line is drawn under the non-African haplotypes to the left, and under the African haplotypes to the right.