Recent admixture between species of the fungal pathogenHistoplasma

Abstract

Hybridization between species of pathogens has the potential to speed evolution of virulence by providing the raw material for adaptation through introgression or by assembling new combinations of virulence traits. Fungal diseases are a source high morbidity, and remain difficult to treat. Yet the frequency of hybridization between fungal species has rarely been explored, and the functional role of introgressed alleles remains largely unknown. Histoplasma mississippiense and H. ohiense are sympatric throughout their range in North America and have distinct virulence strategies, making them an ideal system to examine the role introgression may play in fungal pathogens. We identified introgressed tracts in the genomes of a sample of H. mississippiense and H. ohiense isolates. We found strong evidence in each species for recent admixture, but introgressed alleles were present at low frequencies, suggesting that they were deleterious. Consistent with this, coding and regulatory sequences were strongly depleted within introgressed regions, whereas intergenic regions were enriched, indicating that functional introgressed alleles were frequently deleterious in their new genomic context. Surprisingly, we found only two isolates with substantial admixture: the H. mississippiense and H. ohiense genomic reference strains, WU24 and G217B, respectively. Our results show that recent admixture has occurred, that it is frequently deleterious and that conclusions based on studies of the H. mississippiense and H. ohiense type strains should be revisited with more representative samples from the genus.

Gene exchange between two divergent species of the fungal human pathogen,Coccidioides

“…We obtained size and frequency distributions for each of the two reciprocal directions of introgression. The size of the introgressed haplotypes are ß10-20 kb on average, with only a single introgression in each species larger than 100 Kb, which is far smaller than what had been observed in more recently diverged hybridizing species (e.g., Maxwell et al 2018). Most introgressions are found at low frequency, indicating that admixture is either rare or that introgressed alleles are generally deleterious.…”

“…Four cases have inferred shared ancestry haplotypes consistent with gene exchange and introgression in fungi. In Histoplasma (Maxwell et al 2018) and Magnaporthe (Gladieux et al 2017), admixture seems to be recent as the size of the inferred introgressions (>1 Mb) is large enough to cover several centimorgans. Furthermore, each of these studies examined gene flow between relatively recently (ß2 million years ago) diverged lineages or species (Desjardins et al 2017;Gladieux et al 2017).…”

“…D-statistics can be used to test whether populations have exchanged genes, but they do not identify the location of introgressed haplotypes in the genome. To identify introgressed regions in individuals from the two Coccidioides species, we used a hidden Markov model (HMM), originally designed to detect introgression in diploids (i.e., Int-HMM; Turissini and Matute 2017) that had been modified to detect introgressed haploblocks in haploids (i.e., by assuming no heterozygosity; Maxwell et al 2018). The latter implementation is more suited to Coccidioides as the fungus is haploid (Pan and Cole 1995).…”

“…Transition probabilities determine how likely the HMM in Int-Hmm is to move between the hidden states. We used a transition matrix for haploid individuals as implemented in Maxwell et al (2018). As proposed in the original description of the method (Turissini and Matute 2017), we assumed starting probabilities for each SNP follow a Poisson distribution with a constant recombination rate.…”

“…We used a transition probability between sites for four states that accounts for transitions between biallelic sites and possible error states. As described in Maxwell et al (2018), transition probabilities for haploid organisms follow the form:…”