Data from: Multilocus patterns of genetic variation across Cryptosporidium species suggest balancing selection at the gp60 locus

Cryptosporidium is an apicomplexan protozoan that parasites most vertebrates, including humans. Its gp60 gene is functionally involved in its attachement to host’s cells and its high level of genetic variation has made it the reference marker for sample typing in epidemiological studies. To understand the origin of such high diversity and to determine the extent to which this classification applies to the rest of the genome, we analysed the patterns of variation at gp60 and nine other nuclear loci in isolates of three Cryptosporidium species. Most loci showed low genetic polymorphism (πS < 1%) and similar levels of between-species divergence. Contrastingly, gp60 exhibited very different features: (i) it was nearly ten times more variable than the other loci, (ii) it displayed a significant excess of polymorphisms relative to between-species differences in a Maximum-likelihood Hudson-Kreitman-Aguadé test (iii) gp60 subtypes turned out to be much older than the species they were found in and (iv) showed a significant excess of polymorphic variants shared across species from random expectations. These observations suggest that this locus evolves under balancing selection, and specifically under negative frequency-dependent selection. Interestingly, genetic variation at the other loci cluster very well within the subtypes defined by gp60, which may provide new tools to understand the genome-wide patterns of genetic variation of the parasite in the wild. These results suggest that gp60 plays an active and essential role in the life cycle of the parasite and that genetic variation at this locus might be essential for the parasite’s long-term success.

隐孢子虫（Cryptosporidium）是一类顶复门原生动物，可寄生于包括人类在内的绝大多数脊椎动物宿主。其gp60基因在宿主细胞黏附过程中行使关键功能，该基因极高的遗传变异程度使其成为流行病学研究中样本分型的参考标记基因。为厘清此类高遗传多样性的起源，并明确该分型体系在多大程度上可推广至基因组其余区域，我们对3种隐孢子虫分离株的gp60基因与另外9个核基因座的变异模式展开了分析。多数基因座呈现较低的遗传多态性（πS < 1%），且种间分化水平较为接近。与之形成鲜明反差的是，gp60基因展现出迥异的特征：(i) 其变异幅度几乎是其他基因座的10倍；(ii) 在最大似然Hudson-Kreitman-Aguadé检验（Maximum-likelihood Hudson-Kreitman-Aguadé test）中，该基因座的多态性位点相对于种间差异存在显著过剩；(iii) gp60亚型的演化时间远早于其所在物种的形成时间；(iv) 相较于随机预期，该基因座存在大量跨物种共享的多态性变异，且该差异具有统计学显著性。上述观测结果表明，该基因座处于平衡选择（balancing selection），尤其是负频率依赖选择（negative frequency-dependent selection）的演化选择压力之下。值得注意的是，其余基因座的遗传变异可很好地聚类至gp60定义的亚型框架内，这或许可为解析该寄生虫野外种群的全基因组遗传变异模式提供全新的研究工具。本研究结果提示，gp60基因在寄生虫的生命周期中发挥着活跃且不可或缺的作用，该基因座的遗传变异或许是寄生虫实现长期存续的关键要素。