Mating patterns in seminatural populations of mice influenced by MHC genotype

BECAUSE of the central role of major histocompatibility complex (MHC) genes in immune recognition1–3, it is often assumed that parasite-driven selection maintains the unprecendented genetic diversity of these genes4–7. But associations between MHC genotype and specific infectious diseases have been difficult to identify8,9 with a few exceptions such as Marek's disease10 and malaria11. Alternatively, MHC-related reproductive mechanisms such as selective abortion12–15 and mating preferences16,17 could be responsible for the diversity. To determine both the nature and strength of selection operating on MHC genes by we have studied components of selection in seminatural populations of mice (Mils musculus domesticus). Here we assess MHC-related patterns of reproduction and early (preweaning) mortality by analysing 1,139 progeny born in nine populations, and 662 progeny from laboratory matings. Reproductive mechanisms, primarily mating preferences, result in 27% fewer MHC-homozygous offspring than expected from random mating. MHC genotype had no detectable influence on neonatal (preweaning) mortality. These mating preferences are strong enough to account for most of the MHC genetic diversity found in natural populations of Mus.

[1]  M. Nei,et al.  Population dynamics of sex-determining alleles in honey bees and self-incompatibility alleles in plants. , 1979, Genetics.

[2]  E. Unanue,et al.  Binding of immunogenic peptides to Ia histocompatibility molecules , 1985, Nature.

[3]  E. Boyse,et al.  Recognition among mice. Evidence from the use of a Y-maze differentially scented by congenic mice of different major histocompatibility types , 1979, The Journal of experimental medicine.

[4]  F. Bronson,et al.  The Reproductive Ecology of the House Mouse , 1979, The Quarterly Review of Biology.

[5]  D. Wagener,et al.  HLA sharing and spontaneous abortion in humans. , 1985, American journal of obstetrics and gynecology.

[6]  P. Terasaki,et al.  HLA and Disease Associations , 1985, Springer New York.

[7]  M. Gefter,et al.  Murine MHC polymorphism and T cell specificities. , 1989, Science.

[8]  M. Nei,et al.  Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. , 1990, Genetics.

[9]  Andrew G. Clark,et al.  Evolution at the Molecular Level , 1991 .

[10]  Jerram L. Brown.  Some Paradoxical Goals of Cells and Organisms: The Role of the MHC , 1983 .

[11]  W. Talbot,et al.  The origin of MHC class II gene polymorphism within the genus Mus , 1988, Nature.

[12]  J. Klein.  Natural history of the major histocompatibility complex , 1986 .

[13]  B. Weir,et al.  Mixed self and random mating at two loci. , 1973, Genetical research.

[14]  I. Egorov,et al.  Transgenic Mice and Mutants in MHC Research , 1990, Springer Berlin Heidelberg.

[15]  P. Marrack,et al.  T cell tolerance by clonal elimination in the thymus , 1987, Cell.

[16]  M. Nei,et al.  Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection , 1988, Nature.

[17]  J. Palm.  Proceedings: Maternal-fetal histoincompatibility in rats: an escape from adversity. , 1974, Cancer research.

[18]  M. Feldman,et al.  Further analysis of negative assortative mating. , 1968, Genetics.

[19]  L. Partridge,et al.  The rare-male effect: what is its evolutionary significance? , 1988, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[20]  B J Mathieson,et al.  Control of mating preferences in mice by genes in the major histocompatibility complex , 1976, The Journal of experimental medicine.

[21]  B. Clarke,et al.  Maintenance of Histocompatibility Polymorphisms , 1966, Nature.

[22]  Prim B. Singh,et al.  MHC antigens in urine as olfactory recognition cues , 1987, Nature.

[23]  W. Potts,et al.  Evolution of diversity at the major histocompatibility complex. , 1990, Trends in ecology & evolution.

[24]  R. Zinkernagel,et al.  Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex , 1975, Nature.

[25]  J. M. Smith.  Evolution of sex , 1975, Nature.

[26]  J. Klein,et al.  The population genetics of the H-2 polymorphism in European and North African populations of the house mouse (Mus musculus L.). , 1981, Genetical research.

[27]  D. Pfaff.  Ethical Questions in Brain and Behavior , 1983, Springer New York.