Evolution of loss of heterozygosity patterns in hybrid genomes of Candida yeast pathogens

Background Hybrids are chimeric organisms with highly plastic heterozygous genomes that may confer unique traits enabling the adaptation to new environments. However, most evolutionary theory frameworks predict that the high levels of genetic heterozygosity present in hybrids from divergent parents are likely to result in numerous deleterious epistatic interactions. Under this scenario, selection is expected to favor recombination events resulting in loss of heterozygosity (LOH) affecting genes involved in such negative interactions. Nevertheless, it is so far unknown whether this phenomenon actually drives genomic evolution in natural populations of hybrids. To determine the balance between selection and drift in the evolution of LOH patterns in natural yeast hybrids, we analyzed the genomic sequences from fifty-five hybrid strains of the pathogenic yeasts Candida orthopsilosis and Candida metapsilosis, which derived from at least six distinct natural hybridization events. Results We found that, although LOH patterns in independent hybrid clades share some level of convergence that would not be expected from random occurrence, there is an apparent lack of strong functional selection. Moreover, while mitosis is associated with a limited number of inter-homeologous chromosome recombinations in these genomes, induced DNA breaks seem to increase the LOH rate. We also found that LOH does not accumulate linearly with time in these hybrids. Furthermore, some C. orthopsilosis hybrids present LOH patterns compatible with footprints of meiotic recombination. These meiotic-like patterns are at odds with a lack of evidence of sexual recombination and with our inability to experimentally induce sporulation in these hybrids. Conclusions Our results suggest that genetic drift is the prevailing force shaping LOH patterns in these hybrid genomes. Moreover, the observed LOH patterns suggest that these are likely not the result of continuous accumulation of sporadic events—as expected by mitotic repair of rare chromosomal breaks—but rather of acute episodes involving many LOH events in a short period of time. This work was supported by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. H2020-MSCA-ITN-2014-642095. The TG group also acknowledges the support from the Spanish Ministry of Economy, Industry, and Competitiveness (MEIC) for the EMBL partnership and grants “Centro de Excelencia Severo Ochoa 2013-2017” SEV-2012-0208 and BFU2015-67107 co-founded by the European Regional Development Fund (ERDF); from the CERCA Programme/Generalitat de Catalunya; from the Catalan Research Agency (AGAUR) SGR857 and grants from the European Union’s Horizon 2020 research and innovation program under the grant agreement ERC-2016-724173. TG also receives support from an INB Grant (PT17/0009/0023—ISCIII-SGEFI/ERDF). The authors thank Dr. Powel Golik’s guidance in the identification of PPR proteins, Simone Mozzachiodi and Dr. Gianni Liti for the helpful discussions on the analysis of meiotic patterns, and all Gabaldón lab members for the helpful discussions and comments on this work, especially Marina Marcet-Houben.