230
Sabine S. Loew
Genetic Diversity at Selected Sites: The Case of
the Major Histocompatability Complex
Proponents of the neutral theory argue that most genetic variability at the genomic
or molecular level is selectively neutral and allele frequencies within populations
are merely a function of mutation rate and the effective population size (Kimura
1968; Kimura and Ohta 1971). Neutralists nevertheless agree that deleterious
alleles are eliminated through directional selection and that adaptive evolution is
mediated through fitness differences among alleles (for further discussion, see Li
1997).
The selectionist-neutralist debate has spilled into the conservation biology
arena in discussions about the kind of genetic variation that ought to be preserved
in endangered taxa (Hughes 1991; Vrijenhoek and Leberg 1991; Vrijenhoek 1994;
Avise 1995; Miller 1995; Lynch 1996). Unfortunately, the precise relationships
between most fitness-related traits and genetic diversity at specific allozyme loci,
DNA, or quantitative markers continue to be elusive. Nevertheless, a recent
debate focused on conservation management for maximizing heterozygosity at
fitness-related traits, such as the major histocompatibility complex (MHC)
(Hughes 1991; Vrijenhoek and Leberg 1991; Hedrick and Miller 1994).
MHC molecules play a key role in the immune response of mammals and birds
(possibly all vertebrates) and have been linked to kin recognition based on individual odor profiles in mice (Yamazaki et al. 1979, 1983; Klein 1986; Egid and
Brown 1989; Potts et al. 1991; Brown and Eklund 1994) and possibly humans
(Wedekind et al. 1995). MHC genes encode cell-surface proteins that bind foreign
molecules and aid in recognition and elimination of these potentially harmful
antigens. Extensive allelic diversity at MHC loci has been documented for most
populations studied (Klein 1986; Nei and Hughes 1991). Notable exceptions are
the virtually monomorphic Syrian Hamster, mouse populations on North Sea
islands, and the Cheetah, all of which probably lost overall genetic diversity due to
severe population crashes or small population sizes for many generations (Streilein et al. 1984; McGuire et al. 1985; O’Brien et al. 1985). A variety of mechanisms for maintaining MHC polymorphism have been proposed in the past few
decades (for reviews see Potts and Wakeland 1990; Nei and Hughes 1991; Alberts
and Ober 1993; Klein et al. 1993; Parham and Ohta 1996). The major explanations
include (1) maternal–fetal interactions (Clarke and Kirby 1966; Hedrick and
Thomson 1988), (2) disassortative mating preference based on MHC genotypes
(Yamazaki et al. 1976; Hedrick 1992a; Manning et al. 1992; Wedekind et al.
1995), (3) disease-based overdominance leading to an increased chance of survival in environments with infectious diseases (Doherty and Zinkernagel 1975;
Hughes and Nei 1988; Nei and Hughes 1991), and (4) disease-based frequency
dependence based on the selective advantage of new mutant alleles (Snell 1968;
Bodmer 1972).
The role of pathogen-mediated mechanisms in maintaining MHC variability is
of particular importance to conservation biology. If current high levels of MHC
variability are a consequence of disease-based overdominance selection in the
Sabine S. Loew
Genetic Diversity at Selected Sites: The Case of
the Major Histocompatability Complex
Proponents of the neutral theory argue that most genetic variability at the genomic
or molecular level is selectively neutral and allele frequencies within populations
are merely a function of mutation rate and the effective population size (Kimura
1968; Kimura and Ohta 1971). Neutralists nevertheless agree that deleterious
alleles are eliminated through directional selection and that adaptive evolution is
mediated through fitness differences among alleles (for further discussion, see Li
1997).
The selectionist-neutralist debate has spilled into the conservation biology
arena in discussions about the kind of genetic variation that ought to be preserved
in endangered taxa (Hughes 1991; Vrijenhoek and Leberg 1991; Vrijenhoek 1994;
Avise 1995; Miller 1995; Lynch 1996). Unfortunately, the precise relationships
between most fitness-related traits and genetic diversity at specific allozyme loci,
DNA, or quantitative markers continue to be elusive. Nevertheless, a recent
debate focused on conservation management for maximizing heterozygosity at
fitness-related traits, such as the major histocompatibility complex (MHC)
(Hughes 1991; Vrijenhoek and Leberg 1991; Hedrick and Miller 1994).
MHC molecules play a key role in the immune response of mammals and birds
(possibly all vertebrates) and have been linked to kin recognition based on individual odor profiles in mice (Yamazaki et al. 1979, 1983; Klein 1986; Egid and
Brown 1989; Potts et al. 1991; Brown and Eklund 1994) and possibly humans
(Wedekind et al. 1995). MHC genes encode cell-surface proteins that bind foreign
molecules and aid in recognition and elimination of these potentially harmful
antigens. Extensive allelic diversity at MHC loci has been documented for most
populations studied (Klein 1986; Nei and Hughes 1991). Notable exceptions are
the virtually monomorphic Syrian Hamster, mouse populations on North Sea
islands, and the Cheetah, all of which probably lost overall genetic diversity due to
severe population crashes or small population sizes for many generations (Streilein et al. 1984; McGuire et al. 1985; O’Brien et al. 1985). A variety of mechanisms for maintaining MHC polymorphism have been proposed in the past few
decades (for reviews see Potts and Wakeland 1990; Nei and Hughes 1991; Alberts
and Ober 1993; Klein et al. 1993; Parham and Ohta 1996). The major explanations
include (1) maternal–fetal interactions (Clarke and Kirby 1966; Hedrick and
Thomson 1988), (2) disassortative mating preference based on MHC genotypes
(Yamazaki et al. 1976; Hedrick 1992a; Manning et al. 1992; Wedekind et al.
1995), (3) disease-based overdominance leading to an increased chance of survival in environments with infectious diseases (Doherty and Zinkernagel 1975;
Hughes and Nei 1988; Nei and Hughes 1991), and (4) disease-based frequency
dependence based on the selective advantage of new mutant alleles (Snell 1968;
Bodmer 1972).
The role of pathogen-mediated mechanisms in maintaining MHC variability is
of particular importance to conservation biology. If current high levels of MHC
variability are a consequence of disease-based overdominance selection in the