Pathogen Genomics Group, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
Genome Res. 2009 Dec;19(12):2231-44. doi: 10.1101/gr.097501.109. Epub 2009 Sep 10.
Candida dubliniensis is the closest known relative of Candida albicans, the most pathogenic yeast species in humans. However, despite both species sharing many phenotypic characteristics, including the ability to form true hyphae, C. dubliniensis is a significantly less virulent and less versatile pathogen. Therefore, to identify C. albicans-specific genes that may be responsible for an increased capacity to cause disease, we have sequenced the C. dubliniensis genome and compared it with the known C. albicans genome sequence. Although the two genome sequences are highly similar and synteny is conserved throughout, 168 species-specific genes are identified, including some encoding known hyphal-specific virulence factors, such as the aspartyl proteinases Sap4 and Sap5 and the proposed invasin Als3. Among the 115 pseudogenes confirmed in C. dubliniensis are orthologs of several filamentous growth regulator (FGR) genes that also have suspected roles in pathogenesis. However, the principal differences in genomic repertoire concern expansion of the TLO gene family of putative transcription factors and the IFA family of putative transmembrane proteins in C. albicans, which represent novel candidate virulence-associated factors. The results suggest that the recent evolutionary histories of C. albicans and C. dubliniensis are quite different. While gene families instrumental in pathogenesis have been elaborated in C. albicans, C. dubliniensis has lost genomic capacity and key pathogenic functions. This could explain why C. albicans is a more potent pathogen in humans than C. dubliniensis.
都柏林假丝酵母是白假丝酵母（人类最具致病性的酵母物种）最接近的亲缘种。然而，尽管这两个物种具有许多表型特征，包括形成真正菌丝的能力，但都柏林假丝酵母的毒力和多功能性明显较低。因此，为了鉴定可能导致疾病的白假丝酵母特异性基因，我们对都柏林假丝酵母的基因组进行了测序，并将其与已知的白假丝酵母基因组序列进行了比较。尽管两个基因组序列高度相似且基因排列在整个过程中保持保守，但鉴定出了 168 个种特异性基因，其中包括一些编码已知菌丝特异性毒力因子的基因，如天冬氨酸蛋白酶 Sap4 和 Sap5 以及拟入侵素 Als3。在都柏林假丝酵母中确认的 115 个假基因中，有几个丝状生长调节剂（FGR）基因的同源物，这些基因也可能在发病机制中起作用。然而，基因组库中的主要差异涉及假定转录因子的 TLO 基因家族和白假丝酵母中假定跨膜蛋白的 IFA 家族的扩张，它们代表新的候选毒力相关因子。结果表明，白假丝酵母和都柏林假丝酵母的最近进化历史非常不同。虽然在白假丝酵母中基因家族在发病机制中起重要作用，但都柏林假丝酵母已经失去了基因组能力和关键的致病性功能。这可以解释为什么白假丝酵母比都柏林假丝酵母在人类中更具致病性。
