Deciphering the genetic and gene regulation adaptation strategies of Cryptococcus neoformans passaged in mice of different MHC haplotypes

Abstract

Organisms utilize different mechanisms to adapt or respond to novel environments, including changes to the genome, gene expression, and protein-level functions. This study focused on genome and gene expression changes that occurred when a fungal pathogen encountered new hosts that differed only at a specific immune locus that adapt the immune system. To investigate how a fungal pathogen adapted to the host environment, we obtained genomic and transcriptomic data from strains of Cryptococcus neoformans that were passaged through congenic mice with differences only in the major histocompatibility complex (MHC) locus, H2. I examined the genomic sequence, transcript levels, and transcript structures for each fungal strain and identified one key shared adaptation strategy to a mouse host between all strains. My results indicate that C. neoformans primarily adapted to the mouse host via mutations in the pyrimidine metabolism pathway. However, gene expression changes were identified when strains grown in specific MHC haplotypes were compared. Various metabolic and signaling pathways were changed between strains suggesting that the majority of MHC-specific adaptation occurred at the gene expression level rather than the genomic level. These data suggest that this fungal pathogen has evolved the flexibility to respond to novel environments while maintaining its genomic integrity.