Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus...

Area of Science:

• Mycology
• Genetics
• Evolutionary Biology

Background:

• Hybridization contributes to species origin and variation.
• Mismatch repair pathways, including Msh2, typically block recombination between divergent DNA, maintaining species boundaries.
• Loss of Msh2 increases interspecific recombination in yeast and bacteria.

Purpose of the Study:

• To investigate if Msh2 deficiency relaxes species boundaries between Cryptococcus neoformans and Cryptococcus deneoformans.
• To determine the role of Msh2 in limiting meiotic recombination between these pathogenic fungal species.

Main Methods:

• Crosses were performed between Cryptococcus species lacking Msh2.
• Hybrid progeny were analyzed for viability, aneuploidy, and genetic recombination via whole-genome sequencing.
• Phenotypic analysis of sexual reproduction structures was conducted.

Main Results:

• Msh2-deficient crosses yielded viable hybrid progeny with high aneuploidy.
• Whole-genome sequencing showed limited recombination between species in hybrid progeny.
• No increase in meiotic recombination was observed in progeny from Msh2-deficient parents.
• Novel sexual reproduction phenotypes were observed in some hybrid progeny.

Conclusions:

• Defects in the Msh2 mismatch repair system did not increase meiotic recombination across the Cryptococcus species boundary.
• Alternative pathways or other mismatch repair components likely enforce species boundaries in Cryptococcus.
• This study presents an unexpected case where a key mechanism for preventing interspecific recombination is bypassed without increasing recombination.