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DOI10.1073/pnas.2016818118
Lineage-specific selection and the evolution of virulence in the Candida clade
Singh-Babak S.D.; Babak T.; Fraser H.B.; Johnson A.D.
发表日期2021
ISSN00278424
卷号118期号:12
英文摘要Candida albicans is the most common cause of systemic fungal infections in humans and is considerably more virulent than its closest known relative, Candida dubliniensis. To investigate this difference, we constructed interspecies hybrids and quantified mRNA levels produced from each genome in the hybrid. This approach systematically identified expression differences in orthologous genes arising from cis-regulatory sequence changes that accumulated since the two species last shared a common ancestor, some 10 million y ago. We documented many orthologous gene-expression differences between the two species, and we pursued one striking observation: All 15 genes coding for the enzymes of glycolysis showed higher expression from the C. albicans genome than the C. dubliniensis genome in the interspecies hybrid. This pattern requires evolutionary changes to have occurred at each gene; the fact that they all act in the same direction strongly indicates lineage-specific natural selection as the underlying cause. To test whether these expression differences contribute to virulence, we created a C. dubliniensis strain in which all 15 glycolysis genes were produced at modestly elevated levels and found that this strain had significantly increased virulence in the standard mouse model of systemic infection. These results indicate that small expression differences across a deeply conserved set of metabolism enzymes can play a significant role in the evolution of virulence in fungal pathogens. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Microbial pathogenesis | natural selection | allele-specific expression
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180174
作者单位Department of Microbiology and Immunology, University of California, San Francisco, CA 94158, United States; Assay Development, Lucira Health, Emeryville, CA 94608, United States; Department of Biology, Queens University, Kingston, ON K7L 3N6, Canada; Department of Biology, Stanford University, Stanford, CA 94305, United States; Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, United States; Microbiome Initiative, Chan Zuckerberg Biohub, San Francisco, CA 94158, United States
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Singh-Babak S.D.,Babak T.,Fraser H.B.,et al. Lineage-specific selection and the evolution of virulence in the Candida clade[J],2021,118(12).
APA Singh-Babak S.D.,Babak T.,Fraser H.B.,&Johnson A.D..(2021).Lineage-specific selection and the evolution of virulence in the Candida clade.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA Singh-Babak S.D.,et al."Lineage-specific selection and the evolution of virulence in the Candida clade".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).
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