Coordinated Gene Family Evolution Shapes the Genome of Dimorphic Organisms

Dimorphic organisms possess the remarkable ability to encode within their genomes the information necessary to alternate between two distinct life forms, a choice unavailable to most monomorphic species. However, the evolutionary solution that allows for the integration of genetic information from two divergent life forms into a single dimorphic organism remains unresolved. Here, we investigated this phenomenon using species of Mucorales fungi that are not only capable of growing as either yeast or mycelium but also able to transition reversibly between these forms depending on environmental cues. We have discovered that hundreds of gene families have undergone convergent evolution to adapt their paralogs to the dimorphic lifestyle. This adaptation manifests as the functionalization of paralogs and expression, with some paralogs expressed in the yeast form and others in the mycelial form. Although each of these dimorphic gene families performs distinct and specialized functions, they are all coordinately regulated to achieve differential expression of yeast and mycelium paralogs. Furthermore, distinct gene families with related functions have organized their paralogs into head-to-head (H2H) structures, further enhancing the coordination of their differential expression. This striking coordinated regulation is controlled by two new genes identified in this study (dkl and dfl). Loss of function of these genes results in global dysregulation of gene expression and the consequential loss of dimorphism. Dimorphic gene families, H2H marker loci, and the dfl gene are conserved across various dimorphic species but are absent in closely related monomorphic species. Collectively, dimorphic gene families, their genomic organization, and their specific regulation represent a novel evolutionary mechanism that integrates and optimizes the genetic information required for two distinct life forms within a single organism. Overall design: RNA-seq experiment to analyze the differences in gene expression at the mRNA levels in the yeast-to-hyphae and from mycelium-to-yeast transitions in M. lusitanicus. Total RNA was extracted using the NYZ total RNA kit (NYZtech) and subjected to on-column DNase I treatment (Sigma). Three biological replicates were analyzed for each expression experiment.