Abstract
We sequenced 114 genes (for DNA repair, cell cycle arrest, apoptosis, and detoxification)in a mixed human population and observed a sudden increase in the number of functional polymorphisms below a minor allele frequency of ∼6%. Functionality is assessed by considering the ratio in the number of nonsynonymous single nucletide polymorphisms (SNPs)to the number of synonymous or intron SNPs. This ratio is steady from below 1% in frequency—that regime traditionally associated with rare Mendelian diseases—all the way up to about 6% in frequency, after which it falls precipitously. We consider possible explanations for this threshold effect. There are four candidates as follows: (1)deleterious variants that have yet to be purified from the population, (2)balancing selection, in which a selective advantage accrues to the heterozygotes, (3)population-specific functional polymorphisms, and (4)adaptive variants that are accumulating in the population as a response to the dramatic environmental changes of the last 7,000∼17,000 years.