Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
PLoS Genet. 2012;8(11):e1003057. doi: 10.1371/journal.pgen.1003057. Epub 2012 Nov 15.
Variation in susceptibility to infectious disease often has a substantial genetic component in animal and plant populations. We have used genome-wide association studies (GWAS) in Drosophila melanogaster to identify the genetic basis of variation in susceptibility to viral infection. We found that there is substantially more genetic variation in susceptibility to two viruses that naturally infect D. melanogaster (DCV and DMelSV) than to two viruses isolated from other insects (FHV and DAffSV). Furthermore, this increased variation is caused by a small number of common polymorphisms that have a major effect on resistance and can individually explain up to 47% of the heritability in disease susceptibility. For two of these polymorphisms, it has previously been shown that they have been driven to a high frequency by natural selection. An advantage of GWAS in Drosophila is that the results can be confirmed experimentally. We verified that a gene called pastrel--which was previously not known to have an antiviral function--is associated with DCV-resistance by knocking down its expression by RNAi. Our data suggest that selection for resistance to infectious disease can increase genetic variation by increasing the frequency of major-effect alleles, and this has resulted in a simple genetic basis to variation in virus resistance.
动物和植物种群对传染病的易感性的变化通常具有很大的遗传成分。我们使用黑腹果蝇的全基因组关联研究（GWAS）来确定对病毒感染易感性的遗传基础。我们发现，与从其他昆虫中分离出来的两种病毒（FHV 和 DAffSV）相比，两种自然感染黑腹果蝇的病毒（DCV 和 DMelSV）的易感性存在更多的遗传变异。此外，这种增加的变异是由少数常见的多态性引起的，这些多态性对抗性有重大影响，可以单独解释疾病易感性遗传力的高达 47%。对于其中两种多态性，以前已经表明它们是由自然选择驱动到高频率的。在果蝇中进行 GWAS 的一个优势是，结果可以通过实验来验证。我们通过 RNAi 敲低 pastrel 基因的表达，证实了该基因以前不知道具有抗病毒功能，与 DCV 抗性有关。我们的数据表明，对传染病抗性的选择可以通过增加主要效应等位基因的频率来增加遗传变异，从而导致病毒抗性变异的简单遗传基础。
