Characterization of chimpanzee TCRV gene polymorphism: how old are human TCRV alleles?

Abstract

 The functional relevance of the majority of human T-cell receptor A and B variable region gene polymorphisms is controversial. Studies of human and nonhuman primate major histocompatibility complex (MHC) class I and II polymorphisms show that allelic lineages predate human speciation and indicate that selection favors the long-term maintenance of these advantageous mutations. We investigated at the DNA level whether 15 human TCRA and B polymorphisms exist in contemporary chimpanzee populations. Polymorphisms consisted of variable region replacements, a recombination signal sequence base change, and silent mutations. With one exception, none of these human TCR polymorphisms were observed in contemporary chimpanzees. Investigation of the same polymorphisms in a range of other nonhuman primates showed little evidence of the existence of human polymorphism prespeciation. Chimpanzee TCRAV and BV regions were however polymorphic for variation so far not observed in human groups. Levels of mitochondrial and nuclear DNA sequence variation in contemporary chimpanzees suggest that population bottlenecks have not been a feature of chimpanzee evolution and it is therefore probable that most human TCR polymorphisms have evolved in the estimated five million years since the speciation of human and chimpanzees. Thus, over the evolutionary time period studied, ancient TCRA and B polymorphisms have not been maintained by selection to the same degree as postulated for MHC polymorphisms.