Guo Yaqiong, Tang Kevin, Rowe Lori A, Li Na, Roellig Dawn M, Knipe Kristine, Frace Michael, Yang Chunfu, Feng Yaoyu, Xiao Lihua
State Key Laboratory of Bioreactor Engineering, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, GA, 30333, USA.
BMC Genomics. 2015 Apr 18;16(1):320. doi: 10.1186/s12864-015-1517-1.
Cryptosporidium hominis is a dominant species for human cryptosporidiosis. Within the species, IbA10G2 is the most virulent subtype responsible for all C. hominis-associated outbreaks in Europe and Australia, and is a dominant outbreak subtype in the United States. In recent yearsIaA28R4 is becoming a major new subtype in the United States. In this study, we sequenced the genomes of two field specimens from each of the two subtypes and conducted a comparative genomic analysis of the obtained sequences with those from the only fully sequenced Cryptosporidium parvum genome.
Altogether, 8.59-9.05 Mb of Cryptosporidium sequences in 45-767 assembled contigs were obtained from the four specimens, representing 94.36-99.47% coverage of the expected genome. These genomes had complete synteny in gene organization and 96.86-97.0% and 99.72-99.83% nucleotide sequence similarities to the published genomes of C. parvum and C. hominis, respectively. Several major insertions and deletions were seen between C. hominis and C. parvum genomes, involving mostly members of multicopy gene families near telomeres. The four C. hominis genomes were highly similar to each other and divergent from the reference IaA25R3 genome in some highly polymorphic regions. Major sequence differences among the four specimens sequenced in this study were in the 5' and 3' ends of chromosome 6 and the gp60 region, largely the result of genetic recombination.
The sequence similarity among specimens of the two dominant outbreak subtypes and genetic recombination in chromosome 6, especially around the putative virulence determinant gp60 region, suggest that genetic recombination plays a potential role in the emergence of hyper-transmissible C. hominis subtypes. The high sequence conservation between C. parvum and C. hominis genomes and significant differences in copy numbers of MEDLE family secreted proteins and insulinase-like proteases indicate that telomeric gene duplications could potentially contribute to host expansion in C. parvum.
人隐孢子虫是人类隐孢子虫病的主要病原体。在该物种中，IbA10G2是最具毒性的亚型，导致了欧洲和澳大利亚所有与人隐孢子虫相关的疫情爆发，并且是美国的主要疫情爆发亚型。近年来，IaA28R4在美国正成为一种主要的新亚型。在本研究中，我们对来自这两种亚型的两个野外样本的基因组进行了测序，并将获得的序列与唯一已完全测序的微小隐孢子虫基因组序列进行了比较基因组分析。
从这四个样本中总共获得了45 - 767个组装重叠群中的8.59 - 9.05 Mb隐孢子虫序列，占预期基因组的94.36 - 99.47%。这些基因组在基因组织上具有完全的共线性，与已发表的微小隐孢子虫和人隐孢子虫基因组的核苷酸序列相似性分别为96.86 - 97.0%和99.72 - 99.83%。在人隐孢子虫和微小隐孢子虫基因组之间发现了几个主要的插入和缺失，主要涉及端粒附近多拷贝基因家族的成员。这四个人隐孢子虫基因组彼此高度相似，并且在一些高度多态性区域与参考IaA25R3基因组存在差异。本研究中测序的四个样本之间的主要序列差异位于6号染色体的5'和3'末端以及gp60区域，这主要是基因重组的结果。
两种主要疫情爆发亚型样本之间的序列相似性以及6号染色体上的基因重组，特别是在假定的毒力决定因素gp60区域周围，表明基因重组在高传播性人隐孢子虫亚型的出现中可能发挥作用。微小隐孢子虫和人隐孢子虫基因组之间的高序列保守性以及MEDLE家族分泌蛋白和胰岛素酶样蛋白酶拷贝数的显著差异表明，端粒基因重复可能有助于微小隐孢子虫宿主范围的扩大。
