title: Divergence of protein kinase A catalytic subunits in Cryptococcus neoformans and Cryptococcus gattii illustrates evolutionary reconfiguration of a signaling cascade.
abstract: Gene duplication and divergence via both the loss and gain of gene activities are powerful evolutionary forces underlying the origin of new biological functions. Here a comparative genetics approach was applied to examine the roles of protein kinase A (PKA) catalytic subunits in three closely related varieties or sibling species of the pathogenic fungus genus Cryptococcus. Previous studies revealed that two PKA catalytic subunits, Pka1 and Pka2, control virulence factor production and mating. However, only one of the two plays the predominant physiological role, and this function has been exchanged between Pka1 and Pka2 in strains of the Cryptococcus neoformans var. grubii serotype A lineage compared to divergent C. neoformans var. neoformans serotype D isolates. To understand the basis for this functional plasticity, here the activities of Pka1 and Pka2 were defined in the two varieties and the related sibling species Cryptococcus gattii by gene disruption and characterization, heterologous complementation, and analysis of serotype AD hybrid mutant strains. The findings provide evidence for a shared ancestral role of PKA in governing mating and virulence factor production and indicate that the exchange of catalytic subunit roles is attributable to loss of function. Our studies illustrate the plasticity of signaling networks enabling rapid rewiring during speciation of a clade of common human fungal pathogens.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Dr., Durham, NC 27710, USA.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Hicks
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
mesh_terms: D020134:Catalytic Domain / Q000502:physiology*; D003455:Cryptococcus neoformans / Q000145:classification / Q000201:enzymology* / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000502:physiology; D019143:Evolution, Molecular; D020440:Gene Duplication; D049770:Genes, Mating Type, Fungal / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis; D010802:Phylogeny; D021122:Protein Subunits / Q000737:chemistry* / Q000502:physiology; D012703:Serotyping / Q000145:classification; D015398:Signal Transduction / Q000235:genetics; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D021122:Protein Subunits; D037521:Virulence Factors; D017868:Cyclic AMP-Dependent Protein Kinases