Comparative genomics of the fungal pathogens Candida dubliniensis and Candida albicans
Comparative genomics of the fungal pathogens Candida dubliniensis and Candida albicans
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DOI：
10.1101/gr.097501.109
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发表时间：
2009-12-01
期刊：
影响因子：
7
通讯作者：
Berriman, Matthew
中科院分区：
文献类型：
--
作者：
Jackson, Andrew P.;Gamble, John A.;Berriman, Matthew
都柏林念珠菌是已知的白色念珠菌（人类致病性最强的酵母菌）的最近亲。然而，尽管这两个物种具有许多共同的表型特征，包括形成真正菌丝的能力，但都柏林念珠菌是一种毒性明显较低、用途较少的病原体。因此，为了鉴定可能导致疾病能力增加的白色念珠菌特异性基因，我们对都柏林念珠菌基因组进行了测序，并将其与已知的白色念珠菌基因组序列进行了比较。尽管两个基因组序列高度相似且同线性始终保守，但已鉴定出 168 个物种特异性基因，其中包括一些编码已知菌丝特异性毒力因子的基因，例如天冬氨酰蛋白酶 Sap4 和 Sap5 以及拟议的入侵素 Als3。在都柏林隐球菌中确认的 115 个假基因中，有一些丝状生长调节 (FGR) 基因的直向同源物，这些基因也被怀疑在发病机制中发挥作用。然而，基因组库的主要差异涉及白色念珠菌中假定转录因子的 TLO 基因家族和假定跨膜蛋白的 IFA 家族的扩展，它们代表了新的候选毒力相关因子。结果表明，白色念珠菌和都柏林念珠菌近期的进化史有很大不同。虽然在白色念珠菌中发挥作用的基因家族已被详细阐述，但都柏林念珠菌已经失去了基因组能力和关键致病功能。这可以解释为什么白色念珠菌对人类来说是比都柏林念珠菌更有效的病原体。
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.