Data from: 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.

野生环境中MHC（Major Histocompatibility Complex）多态性对个体适合度变异的影响仍不明确；然而，大量证据表明杂合子优势是关键决定因素。为探究自然种群中MHC多态性对个体疾病抗性或易感性的贡献，我们研究了新西兰海狮（NZSL, Phocarctos hookeri）的两个MHC II类B基因座（loci）——DQB和DRB。新西兰海狮是濒危物种，其幼年期对细菌感染致死具有异常高的易感性；自1997年以来，该物种已发生三次细菌性动物流行病，导致幼崽死亡率居高不下。我们对已知死因（细菌感染、肠炎或创伤）的死亡新西兰海狮幼崽的MHC DQB和DRB单倍型进行了测序与重建，并与存活超过2个月的幼崽进行对比，发现MHC DRB等位基因频率及基因型存在显著差异。两项发现尤为显著：（i）某一DRB等位基因仅存在于死亡幼崽中；（ii）某一在存活幼崽中常见的杂合DRB基因型在死亡幼崽中完全缺失。这些结果表明这些变异具有某种功能关联，并提示DRB基因座存在杂合子优势效应。我们未发现17个微卫星基因座的杂合度与适合度之间存在关联，这表明此处检测到的适合度效应并非由总体杂合度所致。该结果可能是近年来多重病原体侵袭反复选择的结果，同时凸显了MHC基因座的杂合子优势作为野生种群适合度差异潜在机制的重要性。