Heterozygosity and Loss of Heterozygosity in Candida albicans
Germán Larriba and Richard A. Calderone
from: Pathogenic Fungi: Insights in Molecular Biology (Edited by: Gioconda San-Blas and Richard A. Calderone). Caister Academic Press, U.K. (2008)
Although experiments in the early eighties demonstrated the natural auxotrophic heterozygosity of Candida albicans, an accurate estimate of the extent of that heterozygosity in terms of number, nature, and identification of polymorphisms had to wait until the genomic sequence of strain SC5314 and the subsequent elaboration of the diploid assembly was completed. The heterozygosity far exceeds that found in other polymorphic genomes such as human and Anopheles and is widespread among the clinical isolates. Non-synonymous single base polymorphisms (SNP) within a particular ORF result in two proteins that differ in one or several amino acids that may confer functional differences for each protein. This situation considerably increases the number of different proteins encoded by the genome. Furthermore, specific and/or differential expression of both alleles may be controlled by synonymous changes within the ORF or by polymorphisms in the regulatory regions. The high levels of heterozygosity in of a diploid organism with a predominantly clonal mode of propagation suggests that maintenance or even gain of this heterozygosity is essential to maintain genetic diversity within the species. The elucidation of the genetic mechanisms underlying these processes is essential to understand the biology of the organism. Recombination and chromosome loss may modify the levels of heterozygosity, and this may result in the acquisition of new properties, which include assimilation of normally unused sugars, resistance to antifungal compounds, ability to mate, modifications of virulence, etc. Once a certain level of heterozygosity has been reached and a haplotype has been established, mitotic recombination diversifies that haplotype within a particular locus or along the entire chromosome. A parasexual cycle may participate to increase diversity by shuffling alleles of genes that are located in the same or different pair of chromosomes read more ...