Chromosomal Rearrangements between Serotype A and D Strains in Cryptococcus neoformans

Cryptococcus neoformans is a major human pathogenic fungus that can cause meningoencephalitis in immunocompromised hosts. It contains two divergent varieties, var. grubii (serotype A) and var. neoformans (serotype D), as well as hybrids (serotype AD) between these two varieties. In this study, we investigated the extent of chromosomal rearrangements between the two varieties, estimated the effects of chromosomal rearrangements on recombination frequencies, and surveyed the potential polymorphisms of the rearrangements among natural strains of the three serotypes. Through the analyses of two sequenced genomes from strains H99 (representing var. grubii) and JEC21 (representing var. neoformans), we revealed a total of 32 unambiguous chromosome rearrangements, including five translocations, nine simple inversions, and 18 complex rearrangements. Our analyses identified that overall, rearranged regions had recombination frequencies about half of those around syntenic regions. Using a direct PCR screening strategy, we examined the potential polymorphisms of 11 rearrangements among 64 natural C. neoformans strains from five countries. We found no polymorphism within var. neoformans and very limited polymorphism within var. grubii. However, strains of serotype AD showed significant polymorphism, consistent with their hybrid origins coupled with differential loss of heterozygosity. We discuss the implications of these results on the genome structure, ecology, and evolution of C. neoformans.

新型隐球菌（Cryptococcus neoformans）是一种重要的人类致病真菌，可在免疫功能受损的宿主中引发脑膜脑炎。该真菌包含两个分化的变种：grubii变种（血清型A）与neoformans变种（血清型D），以及这两个变种间的杂交株（血清型AD）。本研究针对两类变种间的染色体重排程度展开探究，评估了染色体重排对重组频率的影响，并调查了三类血清型自然菌株中重排的潜在多态性。通过对代表grubii变种的菌株H99与代表neoformans变种的菌株JEC21的两个已测序基因组进行分析，我们共鉴定出32处明确的染色体重排，包括5处易位、9处简单倒位以及18处复杂重排。分析结果显示，整体而言，重排区域的重组频率约为共线性区域周边的一半。我们采用直接PCR筛选策略，对来自5个国家的64株新型隐球菌自然菌株中的11处重排的潜在多态性进行了检测。结果发现，neoformans变种内部未检测到多态性，grubii变种内部的多态性也极为有限。然而，血清型AD菌株则表现出显著的多态性，这与其杂交起源及伴随的差异性杂合性丢失现象相符。本研究还讨论了上述研究结果对新型隐球菌基因组结构、生态学与进化的启示。