Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis, also known as Valley fever in the southwestern United States, Central and South Americas. Coccidioides immitis causes disease along the Pacific range of North America, and is composed of at least 2 populations. Our previous work indicated that C. posadasii is comprised of at least three populations; ARIZONA, TEXAS/MEXICO/SOUTH_AMERICA (TX/MX/SA), and GUATEMALA. The exact range of C. posadasii and its role on human and animal infections in Central and South America is not well defined. The Caribbean region is bordered by the Caribbean Sea, and its surrounding continental landscapes and islands may play an important role in the dispersion of C. posadasii across South America through Southeastern Mexico, Honduras, Guatemala and Venezuela. In order to better define the genetic distribution and population dynamics of C. posadasii in Central and South America, we de novo sequenced the genomes of 6 Coccidioides posadasii clinical isolates from Venezuela, 2 from Mexico as well 1 from Texas and 1 from Florida (USA). We performed phylogenomic and population genomics analysis by incorporating 52 previous deposited genomes from C. posadasii to identify the genetic background of Venezuelan strains and better understand dispersion of this species complex into Central and South America. Comparative phylogenomic analyses of C. posadasii complex reveal that clinical strains from Guatemala and Venezuela are genetically isolated. Population genomics data indicates that limited gene flow exists between GUATEMALA and ARIZONA populations, whereas reproductive isolation from ARIZONA and TX/MX/SA was observed in the GUATEMALA cluster. By using comparative genomics and population genetics tools we provide strong evidence that the South American continent was colonized by at least two ancestral populations: one by a TX/MX/SA ancestral genotype, and the second by a GUATEMALA ancestral genotype. The isolates from Brazil and Paraguay cluster within the TX/MX/SA cluster whereas the Venezuelan clade shares a common ancestor with the Guatemalan cluster and together forms the newly defined CARIBE population. The data suggest that the Venezuela lineage was purified through migration through Central America to the semi-arid regions of Venezuela especially in the coastal plains of the Paraguaná peninsula and the depression valleys of Lara and Falcon states.
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