烟曲霉是一种致命的真菌病原体,负责>400,000感染/年和高死亡率。烟曲霉菌株在感染相关性状方面表现出变异,包括他们的毒力。然而,大多数烟曲霉蛋白质编码基因,包括那些调节其毒力的,在烟曲霉菌株和密切相关的非致病性亲属之间共享。我们假设烟曲霉基因在基因起始密码子上游的非编码区域表现出大量的遗传变异,这可以反映菌株之间基因调控的差异。为了开始测试这个假设,我们在263株烟曲霉的基因组中鉴定了5,812个单拷贝直向同源物。与相应的蛋白质编码区相比,烟曲霉非编码区显示出更高水平的序列变异。具体来说,我们发现,1,274个非编码区表现出<75%的核苷酸序列相似性(与928个蛋白质编码区相比),3,721个非编码区表现出75%至99%的相似性(与2,482个蛋白质编码区相比)。与2,402个蛋白质编码区相比,只有817个非编码区表现出≥99%的序列相似性。通过检查2,482个基因,其蛋白质编码序列同一性得分在75%至99%之间,我们鉴定出478个仅在其非编码区具有阳性选择特征的基因和65个仅在其蛋白质编码区具有特征的基因.选择的478个非编码区中的28个和65个蛋白质编码区中的5个与已知调节烟曲霉毒力的基因相关。烟曲霉菌株之间的非编码区变异包括单核苷酸多态性和至少几个核苷酸的插入或缺失。这些结果表明,烟曲霉基因的非编码区比蛋白质编码区具有更大的序列变异,提出了这种变异可能导致烟曲霉表型异质性的假设。
A.fumigatus is a deadly fungal pathogen, responsible for >400,000 infections/year and high mortality rates. A. fumigatus strains exhibit variation in infection-relevant traits, including in their virulence. However, most A. fumigatus protein-coding genes, including those that modulate its virulence, are shared between A. fumigatus strains and closely related non-pathogenic relatives. We hypothesized that A. fumigatus genes exhibit substantial genetic variation in the non-coding regions immediately upstream to the start codons of genes, which could reflect differences in gene regulation between strains. To begin testing this hypothesis, we identified 5,812 single-copy orthologs across the genomes of 263 A. fumigatus strains. A. fumigatus non-coding regions showed higher levels of sequence variation compared to their corresponding protein-coding regions. Specifically, we found that 1,274 non-coding regions exhibited <75% nucleotide sequence similarity (compared to 928 protein-coding regions) and 3,721 non-coding regions exhibited between 75% and 99% similarity (compared to 2,482 protein-coding regions) across strains. Only 817 non-coding regions exhibited ≥99% sequence similarity compared to 2,402 protein-coding regions. By examining 2,482 genes whose protein-coding sequence identity scores ranged between 75% and 99%, we identified 478 total genes with signatures of positive selection only in their non-coding regions and 65 total genes with signatures only in their protein-coding regions. 28 of the 478 non-coding regions and 5 of the 65 protein-coding regions under selection are associated with genes known to modulate A. fumigatus virulence. Non-coding region variation between A. fumigatus strains included single nucleotide polymorphisms and insertions or deletions of at least a few nucleotides. These results show that non-coding regions of A. fumigatus genes harbor greater sequence variation than protein-coding regions, raising the hypothesis that this variation may contribute to A. fumigatus phenotypic heterogeneity.