X chromosome evidence for ancient human histories

Abstract

Diverse African and non-African samples of the X-linked PDHA1 (pyruvate dehydrogenase E1 ␣ 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 conf lict with microsatellite and mitochondrial data, PDHA1 does not show evidence of human population expansion.

Nucleotide Variation and Haplotype Diversity in a 10-kb Noncoding Region in Three Continental Human Populations

“…These estimates are significantly younger than those estimated from the data at 22q11.2 (1.29 MY), 1q24 (1.47 MY), PDHA1 (1.86 MY), and MC1R (1.52 MY) (Harris and Hey 1999;Zhao et al 2000;Makova et al 2001;Yu et al 2001). However, they are comparable to other estimates based on the data from the b-globin gene (750,000), Xq13.3 (535,000), and Xq21.31 (710,000) (Harding et al 1997;Kaessmann et al 1999;Yu et al 2002b).…”

A population genetics study of the Familial Mediterranean Fever gene: evidence of balancing selection under an overdominance regime

“…This observation, together with the deeper TMRCA of the MEFV minor clade, suggests that haplogroup 3 ( Figures 1 and 2) is accounted for by ancient population structure in the African continent, in line with the idea that African populations have been more subdivided compared with non-African ones. 31,[37][38][39][40][41][42] We used two different methods to infer the TMRCA of the two major MEFV haplotype clades: estimates vary slightly depending on the method used, yielding a rough estimation of B1.70 MY with wide confidence intervals. Estimates of TMRCAs for neutrally evolving autosomal human loci range between 0.8 and 1.5 MY; 42 therefore, the TMRCA we estimated for MEFV, although not exceptional, is deeper than for most neutrally evolving loci.…”

Deep Haplotype Divergence and Long-Range Linkage Disequilibrium at Xp21.1 Provide Evidence That Humans Descend From a Structured Ancestral Population

“…The effects of natural selection on patterns of nucleotide variation tend to be localized to small chromosomal regions (i.e., sites linked to those subject to selection) due to the dissociating effect of recombination. Given that Xp21.1 maps to a region of moderately high recombination ‫9.1ف(‬ cM/Mb; http://genome.ucsc.edu) and (Cann et al 1987;Harpending et al 1998;Harris and Hey 1999; isms is expected, which is not observed at the Xp21.1 locus trio (e.g., Tajima's D ϭ Ϫ0.378). Additionally, Taka Takahata et al 2001;Excoffier 2002).…”

“…Additional coalescent simulations of a 100-fold population reduction occurring ‫001ف‬ KYA yield E(l b ) ϭ 9.70. However, this alternative model is unlikely to be viable for the human population since the effects of a reduced N e (in the absence of population structure) are expected to be visible throughout the entire genome, and no consistent evidence for an ancient African bottleneck has been detected in surveys of nucleotide variation at other loci (Harding et al 1997;Harris and Hey 1999;Ingman et al 2000;Wall and Przeworski 2000;Zhao et al 2000;Alonso and Armour 2001;Frisse et al 2001;Harding and McVean 2004). The effects of natural selection on patterns of nucleotide variation tend to be localized to small chromosomal regions (i.e., sites linked to those subject to selection) due to the dissociating effect of recombination.…”

“…While deep lineages of mtDNA are found in some African hunter-gatherer populations, these lineages trace back only to the time of the global most recent mtDNA ancestor (i.e., Ͻ170 KYA). In contrast, nucleotide variation at the X-linked PDHA1 locus is partitioned into two lineages that are estimated to have diverged in Africa ‫9.1ف‬ million years ago (MYA) (Harris and Hey 1999). This TMRCA is older than expected for an X-linked locus based upon the value of N e estimated from mtDNA and most nuclear variation (Excoffier 2002;Takahata et al 2001).…”