Gene diversity patterns at 10 X-chromosomal loci in humans and chimpanzees

We have investigated the pattern and extent of nucleotide diversityin 10 X-chromosomal genes where mutations are known to causemental retardation in humans. For each gene, we sequenced theentire coding region from cDNA in humans, chimpanzees, and orangutans,as well as about 3 kb of genomic DNA in 20 humans sampled worldwideand in 10 chimpanzees representing two "subspecies." Overallnucleotide diversity in these genes is about twofold lower inhumans than in chimpanzees, and nucleotide diversity withinand between species is low, suggesting that a high level offunctional constraint acts on these genes. Strikingly, we findthat a summary of the allele frequency spectrum is significantlycorrelated in humans and chimpanzees, perhaps reflecting verysimilar levels of constraint at these genes in the two species.A possible exception is FMR2, which shows a higher number ofnonsynonymous than synonymous substitutions on the human lineage,suggesting the action of positive selection.