Heterozygote advantage at MHC DRB may influence response to infectious disease epizootics.
The effect of MHC polymorphism on individual fitness variation in the wild remains equivocal; however, much evidence suggests that heterozygote advantage is a major determinant. To understand the contribution of MHC polymorphism to individual disease resistance or susceptibility in natural populations, we investigated two MHC class II B loci, DQB and DRB, in the New Zealand sea lion (NZSL, Phocarctos hookeri). The NZSL is a threatened species which is unusually susceptible to death by bacterial infection at an early age; it has suffered three bacterial induced epizootics resulting in high mortality levels of young pups since 1997. The MHC DQB and DRB haplotypes of dead NZSL pups with known cause of death (bacteria, enteritis or trauma) were sequenced and reconstructed, compared to pups that survived beyond 2 months of age, and distinct MHC DRB allele frequency and genotype differences were identified. Two findings were striking: (i) one DRB allele was present only in dead pups, and (ii) one heterozygous DRB genotype, common in live pups, was absent from dead pups. These results are consistent with some functional relationship with these variants and suggest heterozygote advantage is operating at DRB. We found no association between heterozygosity and fitness at 17 microsatellite loci, indicating that general heterozygosity is not responsible for the effect on fitness detected here. This result may be a consequence of recurrent selection by multiple pathogen assault over recent years and highlights the importance of heterozygote advantage at MHC as a potential mechanism for fitness differences in wild populations.
Department of Anatomy, University of Otago, PO Box 913, Dunedin, 9054, New Zealand; Department of Pathology, University of Otago, Christchurch, 8140, New Zealand.
Amy J
AJ
Osborne
John
J
Pearson
Sandra S
SS
Negro
B Louise
BL
Chilvers
Martin A
MA
Kennedy
Neil J
NJ
Gemmell
D000818:Animals; D001424:Bacterial Infections / Q000235:genetics / Q000662:veterinary*; D058872:Epidemics; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009520:New Zealand; D046070:Sea Lions / Q000235:genetics* / Q000382:microbiology; D017422:Sequence Analysis, DNA
conservation genetics; disease biology; ecological genetics; mammals; natural selection and contemporary evolution; population genetics-empirical