Department of Biology, University of Central Florida, Orlando, FL, USA.
Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, USA.
Heredity (Edinb). 2021 Apr;126(4):640-655. doi: 10.1038/s41437-020-00402-9. Epub 2021 Jan 28.
Genetic diversity of major histocompatibility complex (MHC) genes is linked to reduced pathogen susceptibility in amphibians, but few studies also examine broad spatial and temporal patterns of MHC and neutral genetic diversity. Here, we characterized range-wide MHC diversity in the Northern leopard frog, Rana pipiens, a species found throughout North America that is experiencing disease-related declines. We used previously sequenced neutral markers (mitochondrial DNA and microsatellites), sequenced an expressed MHC class IIß gene fragment, and measured infection prevalence and intensity of the global fungal pathogen Batrachochytrium dendrobatidis (Bd) across 14 populations. Four populations were sampled across two decades, enabling temporal comparisons of selection and demography. We recovered 37 unique MHC alleles, including 17 that were shared across populations. Phylogenetic and population genetic patterns between MHC and neutral markers were incongruent, and five MHC codon positions associated with peptide binding were under positive selection. MHC heterozygosity, but not neutral marker heterozygosity, was a significant factor explaining spatial patterns of Bd prevalence, whereas only environmental variables predicted Bd intensity. MHC allelic richness (AR) decreased significantly over time but microsatellite-based AR did not, highlighting a loss of functional immunogenetic diversity that may be associated with Bd selective pressures. MHC supertype 4 was significantly associated with an elevated risk of Bd infection, whereas one supertype 2 allele was associated with a nearly significant reduced risk of Bd. Taken together, these results provide evidence that positive selection contributes to MHC class IIß evolution in R. pipiens and suggest that functional MHC differences across populations may contribute to disease adaptation.
主要组织相容性复合体（MHC）基因的遗传多样性与两栖动物病原体易感性降低有关，但很少有研究还考察了 MHC 和中性遗传多样性的广泛时空模式。在这里，我们描述了北豹蛙（Rana pipiens）的全区域 MHC 多样性，北豹蛙是一种分布于北美的物种，由于疾病相关的衰退而受到威胁。我们使用了先前测序的中性标记物（线粒体 DNA 和微卫星），对一个表达的 MHC 类 IIβ基因片段进行了测序，并测量了 14 个种群中全球性真菌病原体蛙壶菌（Batrachochytrium dendrobatidis，Bd）的感染流行率和强度。四个种群在二十年中进行了采样，使选择和人口统计学的时间比较成为可能。我们共回收了 37 个独特的 MHC 等位基因，其中 17 个等位基因在种群间共享。MHC 和中性标记物之间的系统发育和种群遗传模式不一致，五个与肽结合相关的 MHC 密码子位置受到正选择的影响。MHC 杂合性，但不是中性标记物杂合性，是解释 Bd 流行率空间模式的重要因素，而只有环境变量预测了 Bd 强度。MHC 等位基因丰富度（AR）随着时间的推移显著下降，但基于微卫星的 AR 没有下降，这突出了功能性免疫遗传多样性的丧失，这可能与 Bd 的选择压力有关。MHC 超型 4 与 Bd 感染的风险升高显著相关，而一个超型 2 等位基因与 Bd 感染的风险降低显著相关。总的来说，这些结果提供了证据表明正选择导致了北豹蛙 MHC 类 IIβ的进化，并表明种群之间的功能 MHC 差异可能有助于疾病适应。
