Abstract:
In fungi, fusion between individuals leads to localized cell death, a phenomenon termed heterokaryon incompatibility. Generally, the genes responsible for this incompatibility are observed to be under balancing selection resulting from negative frequency-dependent selection. Here, we assess this phenomenon in Aspergillus fumigatus, a human pathogenic fungus with a very low level of linkage disequilibrium as well as an extremely high crossover rate. Using complementation of auxotrophic mutations as an assay for hyphal compatibility, we screened sexual progeny for compatibility to identify genes involved in this process, called het genes. In total, 5/148 (3.4%) offspring were compatible with a parent and 166/2,142 (7.7%) sibling pairs were compatible, consistent with several segregating incompatibility loci. Genetic mapping identified five loci, four of which could be fine mapped to individual genes, of which we tested three through heterologous expression, confirming their causal relationship. Consistent with long-term balancing selection, trans-species polymorphisms were apparent across several sister species, as well as equal allele frequencies within A. fumigatus. Surprisingly, a sliding window genome-wide population-level analysis of an independent dataset did not show increased Tajima\'s D near these loci, in contrast to what is often found surrounding loci under balancing selection. Using available de novo assemblies, we show that these balanced polymorphisms are restricted to several hundred base pairs flanking the coding sequence. In addition to identifying the first het genes in an Aspergillus species, this work highlights the interaction of long-term balancing selection with rapid linkage disequilibrium decay.
摘要:
在真菌中,个体之间的融合导致局部细胞死亡,一种被称为异核体不相容的现象。一般来说,导致这种不相容性的基因被观察到处于由负频率依赖性选择导致的平衡选择下。这里,我们在烟曲霉中评估了这种现象,一种人类致病真菌,具有非常低的连锁不平衡水平以及极高的交叉率。使用营养缺陷型突变的补充作为菌丝相容性的测定方法,我们筛选了性后代的相容性,以鉴定参与这一过程的基因,叫做het基因。总的来说,5/148(3.4%)的后代与父母相容,而166/2142(7.7%)的兄弟姐妹对相容,与几个分离的不相容基因座一致。遗传作图确定了五个基因座,其中四个可以很好地映射到单个基因,其中我们通过异源表达测试了三个,确认其因果关系。与长期平衡选择一致,跨物种多态性在几个姐妹物种中很明显,以及烟曲霉内相同的等位基因频率。令人惊讶的是,对独立数据集的滑动窗口全基因组人群水平分析未显示这些基因座附近的Tajima'sD增加,与在平衡选择下经常发现的周围基因座相反。使用可用的从头程序集,我们表明,这些平衡的多态性仅限于编码序列侧翼的几百个碱基对。除了鉴定曲霉属物种中的第一个het基因,这项工作强调了长期平衡选择与快速连锁不平衡衰减的相互作用。