NATURAL SELECTION AND THE EVOLUTIONARY HISTORY OF MAJOR HISTOCOMPATIBILITY COMPLEX LOCI

Austin L. Hughes and Meredith Yeager

Department of Biology and Institute of Molecular Evolutionary Genetics, The Pennsylvania State University, University Park PA 16802 USA

Received 5/11/98 Accepted 5/22/98

1. ABSTRACT

The major histocompatibility complex (MHC) is a multi-gene family unique to the vertebrates, whose products function to present peptides to T cells. Certain MHC loci are highly polymorphic, and this polymorphism is maintained by a form of balancing selection, probably overdominant selection. This selection has several consequences for MHC biology that make these genes different from neutrally evolving genes: an enhanced rate of nonsynonymous nucleotide substitution in codons encoding the peptide-binding region; long-lasting ("trans-species") polymorphism; and homogenization of introns relative to exons as a result of recombination and subsequent genetic drift. The MHC also reveals evidence of processes shared with other multi-gene families, including gene duplication and deletion and a low level of inter-locus recombination.