Clonality Despite Sex: The Evolution of Host-Associated Sexual Neighborhoods in the Pathogenic Fungus <em>Penicillium marneffei</em>

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.分子遗传学方法通常可检测微生物中的重组现象，无论其被认为是否为无性生殖。然而，遗传学数据显示，艾滋病相关病原体马尔尼菲青霉菌（Penicillium marneffei）在局域和区域尺度上存在广泛的空间遗传结构；尽管已有部分遗传学证据表明其可能存在有性周期，但由于其种群结构高度克隆化，这种单倍体真菌被认为在遗传与形态上均属于无性生物。本研究通过比较基因组学、混合基因型感染实验以及种群遗传学数据，解析重组在马尔尼菲青霉菌自然种群中的作用。全基因组比对分析发现，马尔尼菲青霉菌中存在减数分裂所需的全部基因，其交配型基因的排布方式与其他异宗配合真菌相似，且存在推定的减数分裂特异性突变过程的证据。实验结果表明，亲和交配型菌株之间的重组可能发生在哺乳动物感染过程中。对来自印度、泰国、越南竹鼠的34株分离株，以及中国、印度、泰国、越南人类宿主的273株分离株开展的种群遗传学分析显示，在自然种群中，重组最有可能发生在空间和遗传距离均有限的范围内，这使得该种群既呈现高度克隆化的结构，同时又属于有性繁殖种群。马尔尼菲青霉菌的三个不同空间遗传簇的预测分布，与三种不同竹鼠宿主的分布范围相重叠，这提示宿主内的重组可能是维持马尔尼菲青霉菌种群屏障的关键因素。