Natural Selection in Virulence Genes of Francisella tularensis
Natural Selection in Virulence Genes of Francisella tularensis
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DOI：
10.1007/s00239-016-9743-y
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发表时间：
2016-06-01
影响因子：
3.9
通讯作者：
Adams, Byron J.
中科院分区：
文献类型：
--
作者：
Gunnell, Mark K.;Robison, Richard A.;Adams, Byron J.
进化论的一个基本原则是，处于负选择状态的等位基因通常是有害的，不会带来进化优势。阴性选择的等位基因被从基因库中移除，并最终从种群中消失。相反，正向选择下的等位基因确实赋予进化优势，并导致有机体整体适合度的增加。这些等位基因的频率会增加，直到它们最终在人群中变得固定。图拉氏方济氏菌是一种人畜共患病病原体，也是一种潜在的生物制剂。毒力最强的图拉氏丝虫病A型分布在北美各地，A.I型主要发生在东部，A.II型主要出现在西部。由于在其基因组中存在数量相对较多的假基因，因此图拉氏丝虫被认为是一个衰退中的基因组(丢失基因)。我们假设，观察到的基因丢失/伪基因的频率可能是对不断变化的环境做出反应的进化产物，参与毒力的基因应该处于强烈的正选择之下。为了验证这一假设，我们对A.I型和A.II型分离株的整个基因组进行了测序和比较。我们分析了来自几个亚种基因组的毒力和管家基因的一个子集，以确定正选择的存在和程度。对之前发现的11个毒力基因和10个看家基因进行了正选择筛选。选择分析得到1个看家基因和7个毒力基因，这表明在与细胞表面结构和膜蛋白、代谢和生物合成、转录、翻译和细胞分离以及底物结合和运输有关的基因座上存在明显的正选择。我们的结果表明，虽然负选择可以加速废弃功能基因的丧失，但方氏杆菌基因组的衰退也可能是由宿主、病原体和环境之间复杂的相互作用驱动的适应性进化的副产品，其几个毒力基因正在经历强烈的正选择。
A fundamental tenet of evolution is that alleles that are under negative selection are often deleterious and confer no evolutionary advantage. Negatively selected alleles are removed from the gene pool and are eventually extinguished from the population. Conversely, alleles under positive selection do confer an evolutionary advantage and lead to an increase in the overall fitness of the organism. These alleles increase in frequency until they eventually become fixed in the population. Francisella tularensis is a zoonotic pathogen and a potential biothreat agent. The most virulent type of F. tularensis, Type A, is distributed across North America with Type A.I occurring mainly in the east and Type A.II appearing mainly in the west. F. tularensis is thought to be a genome in decay (losing genes) because of the relatively large number of pseudogenes present in its genome. We hypothesized that the observed frequency of gene loss/pseudogenes may be an artifact of evolution in response to a changing environment, and that genes involved in virulence should be under strong positive selection. To test this hypothesis, we sequenced and compared whole genomes of Type A.I and A.II isolates. We analyzed a subset of virulence and housekeeping genes from several F. tularensis subspecies genomes to ascertain the presence and extent of positive selection. Eleven previously identified virulence genes were screened for positive selection along with 10 housekeeping genes. Analyses of selection yielded one housekeeping gene and 7 virulence genes which showed significant evidence of positive selection at loci implicated in cell surface structures and membrane proteins, metabolism and biosynthesis, transcription, translation and cell separation, and substrate binding and transport. Our results suggest that while the loss of functional genes through disuse could be accelerated by negative selection, the genome decay in Francisella could also be the byproduct of adaptive evolution driven by complex interactions between host, pathogen, and thier environment, as evidenced by several of its virulence genes which are undergoing strong, positive selection.