Data from: Experimental manipulation of population-level MHC diversity controls pathogen virulence evolution in Mus musculus

The virulence levels attained by serial passage of pathogens through similar host genotypes are much higher than observed in natural systems, however, it is unknown what keeps natural virulence levels below these empirically demonstrated maximum levels. One hypothesis suggests that host diversity impedes pathogen virulence, because adaptation to one host genotype carries tradeoffs in the ability to replicate and cause disease in other host genotypes. To test this hypothesis, with the simplest level of population diversity within the loci of the major histocompatibility complex (MHC), we serially passaged Friend Virus Complex (FVC) through two rounds, in hosts with either the same MHC genotypes (pure passage) or hosts with different MHC genotypes (alternated passage). Alternated passages showed a significant overall reduction of viral titer (31%) and virulence (54%) when compared to pure passages. Furthermore, a resistant host genotype initially dominated any effects due to MHC diversity, however, when FVC was allowed to adapt to the resistant host genotype, predicted MHC effects emerged, i.e. alternated lines show reduced virulence. These data indicate serial exposure to diverse MHC genotypes is an impediment to pathogen adaptation, suggesting genetic variation at MHC loci is important for limiting virulence in a rapidly evolving pathogen and supports negative frequency-dependent selection as a force maintaining MHC diversity in host populations.病原体经连续传代至同类宿主基因型后所达到的毒力水平，远高于自然系统中观测到的水平，但目前尚不清楚是什么因素将自然毒力水平维持在这些实验证实的最大阈值之下。有假说提出，宿主多样性会抑制病原体毒力，因为病原体适应某一类宿主基因型后，在其他宿主基因型中复制并致病的能力会产生适应性权衡。为验证该假说，我们以主要组织相容性复合体（major histocompatibility complex, MHC）基因座内最简单的种群多样性水平为模型，将Friend病毒复合体（Friend Virus Complex, FVC）进行两轮连续传代：传代宿主均为相同MHC基因型的纯系传代，或宿主为不同MHC基因型的交替传代。与纯系传代相比，交替传代的病毒滴度（31%）和毒力（54%）总体均出现显著下降。此外，抗性宿主基因型最初会主导MHC多样性带来的所有效应，但当FVC适应了该抗性宿主基因型后，预期的MHC效应便会显现：即交替传代组的毒力显著降低。上述数据表明，连续暴露于多样化MHC基因型会阻碍病原体的适应性进化，这提示MHC基因座的遗传变异对于限制快速进化病原体的毒力至关重要，同时也支持负频率依赖选择作为维持宿主种群MHC多样性的进化动力。