Cryptococcus neoformans is an opportunistic fungal pathogen that is found throughout the world, and is one of the leading killers among HIV+ people in sub-Saharan Africa. Previous population genomic analyses of C. neoformans revealed that there was a large amount of recombination, even in unisexual populations where it wasn’t expected. As recombination can introduce sequence not inherited by vertical descent and therefore skew evolutionary analysis, we decided to re-analyze the impact of recombination with our dataset of 605 isolates representing four major lineages of the pathogen using two different methods. In the first method, we identified and quantified recombinant regions and proceeded to estimate phylogenies of the dataset before and after the recombinant regions were removed. One lineage, VNI, had considerably more recombinant regions than was originally measured with a smaller data set. Notably, we observed a difference in the estimation of phylogenies before and after recombinant regions were identified and removed. In an independent approach, we modeled the recombination of nine Multi Locus Sequence Typing (MLST) genes to find which loci show evidence of recombination between lineages. Interestingly, we observed that one specific gene, SOD1, a super oxide dismutase and known virulence factor, was one of the shared genes with highly similar sequences between lineages. Given our results, we hypothesize that recombination plays a more crucial role in the evolution of C. neoformans than previously assumed and it could potentially be misleading to conduct evolutionary studies without taking into account the impact of recombination.
PROJECT: The impact of recombination on evolutionary inference in Cryptococcus neoformans
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