MHC class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the southern Kalahari
MHC class II DRB variability and parasite load in the striped mouse (Rhabdomys pumilio) in the southern Kalahari
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DOI：
10.1093/molbev/msi112
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发表时间：
2005-05-01
影响因子：
10.7
通讯作者：
Sommer, S
中科院分区：
文献类型：
--
作者：
Froeschke, G;Sommer, S
主要组织相容性复合体（MHC）的变异性被认为是由病原体驱动的选择，通过杂合优势或频率依赖性选择介导。然而，在自然条件下，这些假设的实证支持是罕见的。在这项研究中，我们调查了功能上重要的MHC II类基因（DRB外显子2）的遗传构成和寄生虫负荷的条纹小鼠（小横纹鼠）在南卡拉哈里的人口。58个人进行了遗传学检查和内寄生虫负荷进行了定量计算粪便蠕虫卵通过使用改良的McMaster技术。34只动物（58.6%）被感染。我们鉴定了20种不同的MHC等位基因，等位基因之间具有高水平的序列差异。特别地，抗原结合位点显示非同义替换（d（N））的比率显著高于同义替换（d（S）），这提供了平衡选择的强有力证据。杂合性确实影响感染状态（感染与否）和个体粪卵计数（FEC）值，在纯合个体中观察到显著更高的值。此外，特异性等位基因与寄生虫负荷呈正相关。等位基因Rhpu-DRB*1在感染个体和具有高FEC值（高寄生虫负荷）的个体中显著更频繁地发生。携带Rhpu-DRB*1等位基因的个体比不携带该等位基因的个体感染的几率高1.5倍（比值比检验，P < 0.05）。相反，等位基因Rhpu-DRB*8在FEC值较低的个体中明显更频繁地出现。我们的研究结果支持假设，MHC多态性在R。pumilio是通过杂合性优势和频率依赖性选择共同作用的病原体驱动的选择来维持的。
Major histocompatibility complex (MHC) variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygous advantage or frequency-dependent selection. However, empirical support for these hypotheses under natural conditions is rare. In this study, we investigated the genetic constitution of the functionally important MHC class II gene (DRB exon 2) and the parasite load in a population of the striped mouse (Rhabdomys pumilio) in the Southern Kalahari. Fifty-eight individuals were genetically examined and the endoparasite load was quantified by counting fecal helminth eggs by using a modified McMaster technique. Thirty-four animals (58.6%) were infected. We identified 20 different MHC alleles with high levels of sequence divergence between alleles. Particularly, the antigen-binding sites revealed a significant higher rate of nonsynonymous substitutions (d(N)) than synonymous substitutions (d(S)), giving strong evidence of balancing selection. Heterozygosity did influence the infection status (being infected or not) and the individual fecal egg count (FEC) value with significantly higher values observed in homozygous individuals. Furthermore, a positive relationship was found between specific alleles and parasite load. The allele Rhpu-DRB*1 significantly occurred more frequently in infected individuals and in individuals with high FEC values (high parasite load). Individuals with the allele Rhpu-DRB*1 had a 1.5-fold higher chance of being infected than individuals without this allele (odds ratio test, P < 0.05). Contrarily, the allele Rhpu-DRB*8 significantly occurred more frequent in individuals with low FEC values. Our results support the hypotheses that MHC polymorphism in R. pumilio is maintained through pathogen-driven selection acting by both heterozygosity advantage and frequency-dependent selection.