A strong signature of balancing selection in the 5' cis-regulatory region of CCR5

摘要

CCR5 encodes a cell surface chemokine receptor molecule that serves as the principal coreceptor, with CD4, for HIV-type 1 (HIV-1). Varied HIV-1 susceptibility and time to progression to AIDS have been associated with polymorphisms in CCR5. Many of these polymorphisms are located in the 5' cis-regulatory region of CCR5, suggesting that it may have been a target of natural selection. We characterized CCR5 sequence variation in this region in 400 chro- mosomes from worldwide populations and compared it to a genome-wide analysis of 100 Alu polymorphisms typed in the same populations. Variation was substantially higher than ex- pected and characterized by an excess of intermediate-frequency alleles.