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

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Abstract
Human DNA sequence variation data are useful for studying the origin, evolution, and demographic history of modern humans and the mechanisms of maintenance of genetic variability in human populations, and for detecting linkage association of disease. Here, we report worldwide variation data from a ≈10-kilobase noncoding autosomal region. We identified 75 variant sites in 64 humans (128 sequences) and 463 variant sites among the human, chimpanzee, and orangutan sequences. Statistical tests suggested that the region is selectively neutral. The average nucleotide diversity (π) across 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 (≈0.1%) in humans. The comparable π value in non-Africans to that in Africans indicates no severe bottleneck during the evolution of modern non-Africans; however, the possibility of a mild bottleneck cannot be excluded because non-Africans showed considerably fewer variants than Africans. The present and two previous large data sets all show a strong excess of low frequency variants in comparison to that expected from an equilibrium population, indicating a relatively recent population expansion. The mutation rate was estimated to be 1.15 × 10−9 per nucleotide per year. Estimates of the long-term effective population size Ne by various statistical methods were similar to those in other studies. The age of the most recent common ancestor was estimated to be ≈1.29 million years ago among all of the sequences obtained and ≈634,000 years ago among the non-African sequences, providing the first evidence from a noncoding autosomal region for ancient human histories, even among non-Africans.