Worldwide DNA sequence variation in a 10-kilobase noncoding region on human chromosome 22

Human DNA sequence variation data are useful for studying the origin, evolu tion, and demographic history of modern humans and the mechanisms of mainte nance of genetic variability in human populations, and for detecting linkag e association of disease. Here, we report worldwide variation data from a a pproximate to 10-kilobase noncoding autosomal region. We identified 75 vari ant sites in 64 humans (128 sequences) and 463 variant sites among the huma n, chimpanzee, and orangutan sequences. Statistical tests suggested that th e region is selectively neutral. The average nucleotide diversity (pi) acro ss the region was 0.088% among all of the human sequences obtained, 0.085% among African sequences, and 0.082% among non-African sequences, supporting the view of a low nucleotide diversity (approximate to 0.1%) in humans. Th e comparable pi value in non-Africans to that in Africans indicates no seve re bottleneck during the evolution of modern non-Africans; however, the pos sibility of mild bottleneck cannot be excluded because non-Africans showed considerably fewer variants than Africans. The present and two previous lar ge data sets all show a strong excess of low frequency variants in comparis on to that expected from an equilibrium population, indicating a relatively recent population expansion. The mutation rate was estimated to be 1.15 x 10(-9) per nucleotide per year. Estimates of the long-term effective popula tion size N-e by various statistical methods were similar to those in other studies. The age of the most recent common ancestor was estimated to he ap proximate to 1.29 million years ago among all of the sequences obtained and approximate to 634,000 years ago among the non-African sequences, providin g the first evidence from a noncoding autosomal region for ancient human hi stories, even among non-Africans.