Identification of Allorecognition Loci in Neurospora crassa by Genomics and Evolutionary Approaches.
Identification of Allorecognition Loci in Neurospora crassa by Genomics and Evolutionary Approaches.
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DOI：
10.1093/molbev/msv125
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发表时间：
2015-09
影响因子：
10.7
通讯作者：
Glass NL
中科院分区：
文献类型：
--
作者：
Zhao J;Gladieux P;Hutchison E;Bueche J;Hall C;Perraudeau F;Glass NL
了解区分自我和非自我（同种异体识别）能力的遗传和分子基础以及同种异体识别系统进化的潜在机制对于理解其功能失调的情况（如自身免疫性疾病）是一个重要的努力。在丝状真菌中，同种异体识别可导致营养性或异核体不相容，这是一种基因不同细胞融合后发生的程序性细胞死亡。同种异体识别是由等位基因控制的，不相容等位基因的任何组合的共表达都会引发植物不相容。在此，我们鉴定、表征并推断了丝状真菌粗神经孢子菌候选热位点的进化史。由于已知的het基因座编码携带het结构域的蛋白质，我们利用重测序数据对25个自然种群分离物的het结构域基因和N. crassa参考基因组进行了注释。由于同种异体识别系统可能受到频率依赖选择（即平衡选择）的影响，因此我们挖掘了HET结构域位点的重测序数据，这些位点的等位基因表现出高水平的变异性，中频等位基因过量，以及深层的基因谱系。从这些分析中，34个HET结构域位点被确定为可能处于平衡选择下。通过转化、不亲和性测定和遗传分析，我们确定了这些候选基因中的一个具有热位点（et-e）的功能。et-e位点有三个不同的等位基因群，表现出正选择、群内和群间重组和跨种多态性的特征。我们的研究结果代表了一个令人信服的案例，即在多个基因座上的多个等位基因上平衡选择功能，这些等位基因可能涉及同种异体识别。
Understanding the genetic and molecular bases of the ability to distinguish self from nonself (allorecognition) and mechanisms underlying evolution of allorecognition systems is an important endeavor for understanding cases where it becomes dysfunctional, such as in autoimmune disorders. In filamentous fungi, allorecognition can result in vegetative or heterokaryon incompatibility, which is a type of programmed cell death that occurs following fusion of genetically different cells. Allorecognition is genetically controlled by het loci, with coexpression of any combination of incompatible alleles triggering vegetative incompatibility. Herein, we identified, characterized, and inferred the evolutionary history of candidate het loci in the filamentous fungus Neurospora crassa. As characterized het loci encode proteins carrying an HET domain, we annotated HET domain genes in 25 isolates from a natural population along with the N. crassa reference genome using resequencing data. Because allorecognition systems can be affected by frequency-dependent selection favoring rare alleles (i.e., balancing selection), we mined resequencing data for HET domain loci whose alleles displayed elevated levels of variability, excess of intermediate frequency alleles, and deep gene genealogies. From these analyses, 34 HET domain loci were identified as likely to be under balancing selection. Using transformation, incompatibility assays and genetic analyses, we determined that one of these candidates functioned as a het locus (het-e). The het-e locus has three divergent allelic groups that showed signatures of positive selection, intra- and intergroup recombination, and trans-species polymorphism. Our findings represent a compelling case of balancing selection functioning on multiple alleles across multiple loci potentially involved in allorecognition.