Concerted evolution in the repeats of an immunomodulating cell surface protein, SOWgp, of the human pathogenic fungi Coccidioides immitis and C. posadasii

Abstract

Genome dynamics that allow pathogens to escape host immune responses are fundamental to our understanding of host-pathogen interactions. Here we present the first population-based study of the process of concerted evolution in the repetitive domain of a protein-coding gene. This gene, SOWgp, encodes the immunodominant protein in the parasitic phase of the human pathogenic fungi Coccidioides immitis and C. posadasii. We sequenced the entire gene from strains representing the geographic ranges of the two Coccidioides species. By using phylogenetic and genetic distance analyses we discovered that the repetitive part of SOWgp evolves by concerted evolution, predominantly by the mechanism of unequal crossing over. We implemented a mathematical model originally developed for multigene families to estimate the rate of homogenization and recombination of the repetitive array, and the results indicate that the pattern of concerted evolution is a result of homogenization of repeat units proceeding at a rate close to the nucleotide point mutation rate. The release of the SOWgp molecules by the pathogen during proliferation may mislead the host: we speculate that the pathogen benefits from concerted evolution of repeated domains in SOWgp by an enhanced ability to misdirect the host's immune system.

Figure 1.

Unrooted consensus tree of repeat sequences from strains of C. immitis and C. posadasii. Bootstrap values of >50% are given by the branches. Repeats are named as follows: i, immitis; p, posadasii; RMSCC strain number; repeat x out of (y). Edge repeats are encircled with green for C. immitis and red for C. posadasii. C. immitis internal repeats are encircled with yellow.

Figure 2.

Average genetic distance between sequences of repeats at different physical distances in the array. 0, corresponding position; 1, adjacent position; 2–4, separated by one to three repeats. (A) All repeats included; (B) only internal repeats included. The bars represent mean values ±SE for all genetic distances at each position.