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 two 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; 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.目前学界对于主要组织相容性复合体（Major Histocompatibility Complex，MHC）多态性对野生种群个体适合度变异的影响尚未达成共识，但大量研究证据表明，杂合子优势是其主要决定因素之一。为探究MHC多态性对自然种群个体疾病抗性与易感性的贡献，我们以新西兰海狮（New Zealand sea lion, NZSL, *Phocarctos hookeri*）为研究对象，对其两个MHC II类B基因座位——DQB与DRB展开了分析。新西兰海狮属于受威胁物种，其幼崽极易在幼年阶段因细菌感染死亡；自1997年以来，该种群已先后爆发三次由细菌引发的兽疫，导致幼崽死亡率居高不下。我们对已知死亡原因（细菌感染、肠炎或外伤）的死亡幼崽的MHC DQB与DRB单倍型进行了测序与构建，并与存活超过2月龄的幼崽进行对照分析，结果发现MHC DRB等位基因频率与基因型存在显著差异。有两项发现尤为引人注目：其一，某一DRB等位基因仅在死亡幼崽中存在；其二，在存活幼崽中较为常见的某一DRB杂合基因型，并未在死亡幼崽中被检测到。上述结果与这些变异体间存在一定功能关联的情形相符，同时表明DRB座位存在杂合子优势效应。我们对17个微卫星（microsatellite）座位的分析未发现杂合度与适合度之间存在显著关联，这表明本研究中观测到的适合度差异并非由整体杂合度所导致。该结果可能是近年来多种病原体持续侵染引发的反复选择的结果，同时凸显了MHC座位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。