Using BLAST to Detect Horizontal Gene Transfer in Pathogenic Fungi

By Christopher Good

Faculty Mentor: Professor Theresa Grana

Similarly to antibiotic resistance, antifungal resistance is a growing challenge for clinicians. Mechanistically, one method of antibiotic resistance acquisition is through horizontal gene transfer (HGT). Although associated more with prokaryotes, past studies show limited evidence of HGT in Candida yeast, warranting additional comparative, genomic and proteomic research on the evolutionary forces behind fungal virulence. This honors capstone project used the NCBI’s Basic Local Alignment Search Tool (BLAST) to quickly and statistically compare existing biological sequence data in conjunction with EMBL Multiple Sequence Comparison by Log-Expectation (MUSCLE) alignment and Molecular Evolutionary Genetics Analysis (MEGA) to visualize likely evolutionary relationships. Thus, the objective of this project was to use bioinformatics tools to identify potential instances of Horizontal Gene Transfer (HGT) between pathogenic yeast and viruses, specifically HGT as an evolutionary mechanism for antifungal resistance gene (ARG) acquisition. Of the subset of ARGs searched, BLAST showed more support for ERG3 (C-5 sterol desaturase) HGT between edafosvirus and C. glabrata and between orpheovirus and C. albicans and C. californica, respectively. However, the ML phylogeny contradicts these BLAST results and shows more support for ERG3 HGT between both viruses and Hypopichia burtonii. Thus, while BLAST showed limited evidence for ERG3 HGT between three Candida species and two viruses, the ML phylogeny fails to support these evolutionary events. For the purposes of HGT, BLAST might be better suited to certain organisms (i.e., prokaryotes) and its use should be reinforced as a non-definitive predictor of such evolutionary events. Furthermore, increased understanding of the numerous uncharacterized Candida genes could reveal new evidence of fungal HGT and guide treatment options. Word Count: 261