Clonality despite sex: the evolution of host-associated sexual neighborhoods in the pathogenic fungus Penicillium marneffei.

Daniel A Henk,Alex Andrianopoulos,Heiman Wertheim,Nguyen Van Kinh,Po-Ren Hsueh,William C Nierman,Nengyong Zhan,Nongnuch Vanittanakom,Khuraijam Ranjana Devi,Matthew C Fisher,Revital Shahar-Golan,Natalie D Fedorova,Elaine M Bignell,Kwok-Yung Yuen,Kylie J Boyce,Tran P M Sieu,Stephen G Baker,Jeremy N Day,Bruce A Mcdonald

doi:10.1371/journal.ppat.1002851

Abstract

Molecular genetic approaches typically detect recombination in microbes regardless of assumed asexuality. However, genetic data have shown the AIDS-associated pathogen Penicillium marneffei to have extensive spatial genetic structure at local and regional scales, and although there has been some genetic evidence that a sexual cycle is possible, this haploid fungus is thought to be genetically, as well as morphologically, asexual in nature because of its highly clonal population structure. Here we use comparative genomics, experimental mixed-genotype infections, and population genetic data to elucidate the role of recombination in natural populations of P. marneffei. Genome wide comparisons reveal that all the genes required for meiosis are present in P. marneffei, mating type genes are arranged in a similar manner to that found in other heterothallic fungi, and there is evidence of a putatively meiosis-specific mutational process. Experiments suggest that recombination between isolates of compatible mating types may occur during mammal infection. Population genetic data from 34 isolates from bamboo rats in India, Thailand and Vietnam, and 273 isolates from humans in China, India, Thailand, and Vietnam show that recombination is most likely to occur across spatially and genetically limited distances in natural populations resulting in highly clonal population structure yet sexually reproducing populations. Predicted distributions of three different spatial genetic clusters within P. marneffei overlap with three different bamboo rat host distributions suggesting that recombination within hosts may act to maintain population barriers within P. marneffei.

Highlights

Hypotheses of globally continuous populations and strict clonality in putatively asexual microbial pathogens are rarely supported [1,2,3,4,5]
Previous studies have shown that P. marneffei has a pattern of extreme clonality despite the ability to disperse across wide distances and the presence of mating type genes that are required for sexual recombination
In this study we used genetic markers, comparative genomics, experimental data, and spatial models to determine the influence of sex on P. marneffei populations, and we found that there was substantial evidence of sexual recombination, most of the recombination in natural populations was limited to sexual neighborhoods, amongst genetically similar and spatially close individuals

Summary

Introduction

Hypotheses of globally continuous populations and strict clonality in putatively asexual microbial pathogens are rarely supported [1,2,3,4,5]. Genetic approaches detect recombination in microbes regardless of assumed asexuality, and pathogens are surprisingly promiscuous despite strong population genetic structure [6,7,8]. Examples that cause extensive morbidity include Cryptococcus neoformans, Coccidioides sp., Histoplasma capsulatum and Penicillium marneffei. These fungi are maintained in natural environmental reservoirs that might contribute to structured populations via local adaptation, and they are thought to be largely clonal.

Author Summary

Findings

Materials and Methods