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Impact of Genetic Background on Allele Selection in a Highly Mutable Candida albicans Gene, PNG

Citation

Zhang, N and Cannon, RD and Holland, BR and Patchett, ML and Schmid, J, Impact of Genetic Background on Allele Selection in a Highly Mutable Candida albicans Gene, PNG, PLOS One, 5, (3) EJ ISSN 1932-6203 (2010) [Refereed Article]


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Copyright Statement

Copyright: © 2010 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI: doi:10.1371/journal.pone.0009614

Abstract

In many microbes rapid mutation of highly mutable contingency genes continually replenishes a pool of variant alleles from which the most suitable are selected, assisting in rapid adaptation and evasion of the immune response. In some contingency genes mutability is achieved through DNA repeats within the coding region. The fungal human pathogen Candida albicans has 2600 repeat-containing ORFs. For those investigated (ALS genes, HYR1, HYR2, CEK1, RLM1) many protein variants with differing amino acid repeat regions exist, as expected for contingency genes. However, specific alleles dominate in different clades, which is unexpected if allele variation is used for short-term adaptation. Generation of new alleles of repeat-containing C. albicans ORFs has never been observed directly. Here we present evidence for restrictions on the emergence of new alleles in a highly mutable C. albicans repeat-containing ORF, PNG2, encoding a putative secreted or cell surface glycoamidase. In laboratory cultures new PNG2 alleles arose at a rate of 2.861025 (confidence interval 3.36102629. 961025) per cell per division, comparable to rates measured for contingency genes. Among 80 clinical isolates 17 alleles of different length and 23 allele combinations were distinguishable; sequence differences between repeat regions of identical size suggest the existence of 36 protein variants. Specific allele combinations predominated in different genetic backgrounds, as defined by DNA fingerprinting and multilocus sequence typing. Given the PNG2 mutation rate, this is unexpected, unless in different genetic backgrounds selection favors different alleles. Specific alleles or allele combinations were not preferentially associated with C. albicans isolates from particular body sites or geographical regions. Our results suggest that the mutability of PNG2 is not used for short-term adaptation or evasion of the immune system. Nevertheless the large number of alleles observed indicates that mutability of PNG2 may assist C. albicans strains from different genetic backgrounds optimize their interaction with the host in the long term.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Microbiology
Research Field:Microbial Genetics
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Holland, BR (Associate Professor Barbara Holland)
ID Code:63293
Year Published:2010
Web of Science® Times Cited:5
Deposited By:Mathematics
Deposited On:2010-04-27
Last Modified:2010-05-05
Downloads:249 View Download Statistics

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