Study of subtelomeric recombination and stress response in the yeasts Candida albicans and Kluyveromyces lactis
Griffith, Paul Michael
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Subtelomeres are specialized regions adjacent to the chromosome end of DNA/protein structures known as telomeres. These regions experience distinct differences in mutation rate, recombination rate, gene density, and gene silencing which provide a unique environment in which to promote rapid evolution. Subtelomeres may utilize adjacent telomeres as drivers of evolution in response to stress conditions, which may generate transient telomeric dysfunction through sequence modification or protein association modifications and in turn promote telomere recombination. Telomeric recombination has been shown to promote subtelomeric recombination and this process may be used to drive subtelomeric evolution. In this way, the rapid evolution of contingency gene families found at subtelomeric sites may occur through gene duplication and subsequence diversification to provide means of adapting to the surrounding environments. The Adaptive Telomere Failure hypothesis provides a model by which an organism may utilize programmed stress-related telomeric dysfunction to drive the subtelomeric architecture into a evolutionarily active state by promoting increased rates of recombination. To study the role in which subtelomeric recombination plays as part of the milk yeast Kluyveromyces lactis and the human pathogen Candida albicans and its response to stress conditions, URA3 biosynthetic markers and a naturally occurring β-galactosidase were utilized to study single strand annealing (SSA) and break induced replication (BIR) recombinational pathways at subtelomeric and non-subtelomeric loci. K. lactis was found to demonstrate a significant increase in recombination at subtelomeric sites in response to certain stress conditions including exposure to arsenate, but not other stresses. Additionally, we found that exposure to sodium arsenate stress produced reversible slower growing colony morphologies even after removal from arsenate. Finally, studies in C. albicans provided evidence to support a varied rate of subtelomeric recombination among multiple members of the subtelomeric TLO gene family that is transcriptionally modulated during stress conditions.