Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen
Year: 2018
Type: article
Abstract: Candida albicans is a heterozygous diploid yeast that is a commensal of the human gastrointestinal (GI) tract and a prevalent opportunistic pathogen. Here, whole-genome sequencing was performed on multiple C. albicans isolates passaged in different niches to characterize the complete spectrum of mutations arising during microevolution. We reveal that evolution during short time-scales (<600 generations) is driven by both de novo base substitutions and short-tract loss of heterozygosity (LOH) events. In contrast, large-scale chromosomal changes are relatively rare, although chromosome 7 trisomies repeatedly emerged during passaging in one GI colonization model. Both strain background and chromosomal features affected mutational patterns, with mutation rates being greatly elevated in regions adjacent to emergent LOH tracts. Mutation rates were also elevated during host infection where genomes showed strong evidence of purifying selection. These results establish the genetic events driving C. albicans evolution and that this heterozygous diploid is extensively shaped by purifying selection.
Institutions: Brown University, Broad Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Funders: U.S. Department of Health and Human Services, Burroughs Wellcome Fund, Sigma Delta Epsilon-Graduate Women in Science, Massachusetts Institute of Technology, Wellcome Trust, Broad Institute, Graduate Women in Science, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Dental and Craniofacial Research
Awards: G100359263, G1044601524, Parasexual Genetics and Host Adaptation in Candida Fungal Pathogens, Advancing genomic, transcriptomic and functional approaches to combat globally important and emerging pathogens, G1442055599, Development of Quantitative Genetics Approaches in Candida albicans, G2898696312, G3708211351, Transcriptional Regulation of C. albicans Cell Fate and Host Interactions, G4914387008, G5679901488, G5729080129, G6969247893, Defining the Roles of Perseverance and Heteroresistance in Persistent Human Fungal Infections, G7313007295, Genotypic plasticity and parasex in Candida albicans, G9000209541
OpenAlex ID: W2889392906