Genome evolution in the Candida clade (360G-Wellcome-109165_Z_15_A)

The CUG-Serine clade, a group of yeasts including the common human pathogen Candida albicans, has been known to translate the codon CUG as serine instead of leucine for over 20 years. Recently, a sister species that translates CUG as alanine was discovered. In my bioinformatics rotation I discovered a second, independent CUG-Ser clade as well as a CUG-Ala clade and three separate CUG-Leu clades.In my PhD project I will examine tRNA gene evolution in these clades and test the hypothesis that they descended from a catastrophic event in their common ancestor in which the CUG- decoding tRNA was lost. I will perform experiments to artificially push a yeast species to change its CUG translation from Ser to Leu by replacing a tRNA gene, and monitor the effect on the proteome. In parallel, I will study centromere evolution in yeasts, which show an extraordinary diversity of centromere types, by using ChiP-seq to find centromeres across the Candida clade and beyond. This project will develop valuable new tools for manipulating Candida genomes, including transformation vectors that completely lack CUG codons and should work in any species, and potentially also new centromere-based plasmids for use in C. albicans.