Genetic variability in the major histocompatibility complex: A review of non-pathogen-mediated selective mechanisms

The extraordinary genetic polymorphism observed in the major histocompatibility complex (MHC) of the vertebrate genome has attracted the attention of researchers for decades. In almost all taxa that have been investigated, levels of polymorphism are remarkably high. Several mechanisms have been proposed to explain the maintenance of genetic diversity at the MHC, including pathogen-driven natural selection, selection driven by maternal-fetal interactions, and negative assortative mating. In this review we discuss the evidence for the latter two mechanisms in human and animal populations. We begin with a description of the structure and function of the MHC, particularly in humans. Then, evidence for natural selection acting on MHC genes, in the form of homozygote deficiencies observed in human population isolates, is discussed. The two major candidates for mechanisms of non-pathogen-driven selection, maternal-fetal interactions and MHC-based mate choice, are described in detail and their implications are discussed.