Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30602, USA.
BMC Genomics. 2011 Mar 7;12:139. doi: 10.1186/1471-2164-12-139.
Trypanosoma cruzi is a protozoan parasite and the etiologic agent of Chagas disease, an important public health problem in Latin America. T. cruzi is diploid, almost exclusively asexual, and displays an extraordinarily diverse population structure both genetically and phenotypically. Yet, to date the genotypic diversity of T. cruzi and its relationship, if any, to biological diversity have not been studied at the whole genome level.
In this study, we used whole genome oligonucleotide tiling arrays to compare gene content in biologically disparate T. cruzi strains by comparative genomic hybridization (CGH). We observed that T. cruzi strains display widespread and focal copy number variations (CNV) and a substantially greater level of diversity than can be adequately defined by the current genetic typing methods. As expected, CNV were particularly frequent in gene family-rich regions containing mucins and trans-sialidases but were also evident in core genes. Gene groups that showed little variation in copy numbers among the strains tested included those encoding protein kinases and ribosomal proteins, suggesting these loci were less permissive to CNV. Moreover, frequent variation in chromosome copy numbers were observed, and chromosome-specific CNV signatures were shared by genetically divergent T. cruzi strains.
The large number of CNV, over 4,000, reported here uphold at a whole genome level the long held paradigm of extraordinary genome plasticity among T. cruzi strains. Moreover, the fact that these heritable markers do not parse T. cruzi strains along the same lines as traditional typing methods is strongly suggestive of genetic exchange playing a major role in T. cruzi population structure and biology.
克氏锥虫是一种原生动物寄生虫，也是恰加斯病的病原体，恰加斯病是拉丁美洲的一个重要公共卫生问题。克氏锥虫是二倍体，几乎完全是无性繁殖，在遗传和表型上表现出极其多样的群体结构。然而，迄今为止，克氏锥虫的基因型多样性及其与生物学多样性的关系尚未在全基因组水平上进行研究。
在这项研究中，我们使用全基因组寡核苷酸平铺阵列通过比较基因组杂交（CGH）来比较生物差异的克氏锥虫株的基因含量。我们观察到，克氏锥虫株显示出广泛和局灶性的拷贝数变异（CNV），并且其多样性水平远超过当前遗传分型方法所能充分定义的水平。正如预期的那样，CNV 在富含粘蛋白和转涎酸酶的基因家族丰富的区域特别频繁，但在核心基因中也很明显。在测试的菌株中，基因拷贝数变化很小的基因组包括编码蛋白激酶和核糖体蛋白的基因组，这表明这些基因座对 CNV 的容忍度较低。此外，还观察到染色体拷贝数的频繁变化，并且遗传上不同的克氏锥虫株共享染色体特异性的 CNV 特征。
这里报告的超过 4000 个 CNV 数量之多，在全基因组水平上支持了克氏锥虫株之间基因组高度可塑性的长期观点。此外，这些可遗传的标记不能按照传统的分型方法将克氏锥虫株分开，这强烈表明遗传交换在克氏锥虫群体结构和生物学中起着重要作用。
