Population genomic sequencing of Coccidioides fungi reveals recent hybridization and transposon control

Abstract

We have sequenced the genomes of 18 isolates of the closely related human pathogenic fungi Coccidioides immitis and Coccidioides posadasii to more clearly elucidate population genomic structure, bringing the total number of sequenced genomes for each species to 10. Our data confirm earlier microsatellite-based findings that these species are genetically differentiated, but our population genomics approach reveals that hybridization and genetic introgression have recently occurred between the two species. The directionality of introgression is primarily from C. posadasii to C. immitis, and we find more than 800 genes exhibiting strong evidence of introgression in one or more sequenced isolates. We performed PCRbased sequencing of one region exhibiting introgression in 40 C. immitis isolates to confirm and better define the extent of gene flow between the species. We find more coding sequence than expected by chance in the introgressed regions, suggesting that natural selection may play a role in the observed genetic exchange. We find notable heterogeneity in repetitive sequence composition among the sequenced genomes and present the first detailed genome-wide profile of a repeat-induced point mutation (RIP) process distinctly different from what has been observed in Neurospora. We identify promiscuous HLA-I and HLA-II epitopes in both proteomes and discuss the possible implications of introgression and population genomic data for public health and vaccine candidate prioritization. This study highlights the importance of population genomic data for detecting subtle but potentially important phenomena such as introgression.

Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity

“…There is some hybridization between the two species [6,35]. Sequencing of a large number of clinical isolates in Arizona established that almost all were genetically diverse strains of C. posadasii [8].…”

“…At least four chromosomes have been identified by contour-clamped homogeneous electric field gel electrophoresis [36]. The genomes are haploid and no mating has been observed within or between species, although genes coding for mating functions are present [2] and genetic recombination occurs [35]. About 18% of the genome consists of repetitive DNA.…”

“…Coccidioides spp. appear to have a repeat-induced mutation mechanism to control proliferation of transposons [35]. Both DNA and long terminal repeat transposons are found; Gypsy, which is a retrovirus-like transposon that is common in fungi, is the most common type of transposon.…”

Toward genome-enabled mycology

“…At the level of populations, genomewide association studies (McCarthy et al 2008) based on single nucleotide polymorphisms (SNPs) will provide the ability to characterize variation at the nucleotide level across the genome, with much greater granularity than traditional QTL approaches. Such analyses are already revolutionizing population genetic studies of fungi, providing insight into mechanisms of adaptation and population divergence (Cowen et al 2002, Tsai et al 2008, Neafsey et al 2010, Ellison et al 2011, Louis 2011.…”

The Powers and Perils of PCR in the Search for the Natural Reservoirs of Coccidioides Species

“…Coccidioides immitis and C. posadasii are two distinct species distinguished by multilocus sequencing typing (MLST) and other genetic analyses [2,5,6]. Coccidioides posadasii represents the entire nonCalifornia population of the pathogen.…”