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

Abstract

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. o 1993 Wiiey-Lisa, IncThe major histocompatibility complex (MHC) encompasses a cluster of genes that have remarkable genetic characteristics. Present in all vertebrates examined to date, the MHC has been a major focus of investigations by geneticists, evolutionary biologists, and anthropologists, who have characterized and tried to elucidate the mechanisms that underlie these extraordinary features. Among its characteristics is the extreme polymorphism of many genes in the complex, which have large numbers of alleles, most of which are present at appreciable frequencies in natural populations. Up to 92 identified alleles per locus are present in mice, and high levels of polymorphism and heterozygosity have been found in almost all other taxa that have been investigated (Klein, 1986). The human MHC, known as the human leukocyte antigen (HLA) region, includes at least 20 HLA-A, 40 HLA-B, 10 HLA-C, 14 HLA-DR, 7 HLA-DQ, and 6 HLA-DP alleles identifiable by serological techniques (Bodmer et al., 1991). Additional alleles can be identified by isoelectric focusing (Yang, 1987) and molecular genetic analysis (Tsuji et al., 1992). Rarely does the frequency of any one allele exceed 30% in any population. As a result, homozygotes for HLA alleles are infrequent in the population and most individuals are heterozygous at each locus.Considerable interest has been generated in possible mechanisms for maintaining the high levels of polymorphism and heterozygosity at MHC loci. Nei (1988,1989) demonstrated that polymorphism in some human MHC regions is 0 1993 Wiley-Liss, Inc.

Wild female baboons bias their social behaviour towards paternal half-sisters

“…It is highly genetically variable and appears to affect mate-choice decisions in mice (Egid & Brown 1989;Potts et al 1991) and humans (Ober et al 1997; but see Hedrick & Black 1997). MHC variation in natural populations, and its effect on behaviour, remain understudied (see reviews in Alberts & Ober 1993;Brown & Eklund 1994;Penn & Potts 1999). …”

The evolutionary ecology of the major histocompatibility complex

“…A number of adaptive hypotheses, which are not necessarily mutually exclusive, have been proposed to explain how MHC could influence mating behaviour and reproductive success. Those that have received most attention are: (1) MHC-related selective fertilisation (Wedekind et al, 1996;Rulicke et al, 1998;Wedekind et al, 2004); (2) MHC-dependent selective abortion (Alberts and Ober, 1993); (3) disassortative matings based on MHC genotype (Penn and Potts, 1999). Here, we focus on the latter, as this has been the primary focus for studies in non-model vertebrates.…”

Increased heterozygosity for MHC class II lineages in newborn males

“…[1][2][3][4][5][6] In vertebrate animals, no such system is known but there is some evidence that the major histocompatibility complex (MHC) may be acting as a genetic compatibility system. [6][7][8][9][10][11] The MHC is primarily involved in immunological functions…”