Genetic evidence for the spread of a benzimidazole resistance mutation across southern India from a single origin in the parasitic nematode Haemonchus contortus
Genetic evidence for the spread of a benzimidazole resistance mutation across southern India from a single origin in the parasitic nematode Haemonchus contortus
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DOI：
10.1016/j.ijpara.2015.04.007
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发表时间：
2015-09-01
影响因子：
4
通讯作者：
Gilleard, John S.
中科院分区：
文献类型：
--
作者：
Chaudhry, Umer;Redman, Elizabeth M.;Gilleard, John S.
了解驱虫药耐药突变是如何产生和传播的，以确定适当的缓解策略是很重要的。我们假设，对印度南部弯血蜱（Haemonchus contortus）的分子遗传学研究，可能会为虫虫耐药性的起源和传播提供一些重要的见解，该地区的耐药性可能不如西欧和北美发达。F200Y （barC下的T (A)）同型1 β -微管蛋白苯并并唑耐药突变在世界各地的弯毛鼠中都很常见，F167Y （barC下的T (A)）和E198A （barA下的G (C)）突变虽然不太常见，但在许多不同的国家都有报道。本文研究了印度南部23个小反刍动物弯鼠种群中β -微管蛋白苯并咪唑抗性等位基因的单倍型多样性和系统发育关系。F200Y （barC下的T (A)）突变最常见，在18123个群体中检测到，频率在9% ~ 84%之间；E198A （G (C)）突变在8/23个群体中检测到，频率在8% ~ 18%之间。在23个群体中均未检测到F167Y （barC下的T (C)）突变。系统发育单倍型网络分析表明，F200Y （T (A) under barC）突变在该地区发生了多次独立的突变，在调查人群中至少有三个独立的抗性等位基因起源。相比之下，E198A （barA下的G (C)）突变出现在单一单倍型上，考虑到该地区易感等位基因的高水平单倍型多样性，这表明这种特殊的突变可能是通过人为的动物运动从单一起源传播的。利用8个微卫星标记对12个弯齿人居群进行群体遗传分析，结果表明弯齿人居群间遗传分化极低，符合位点间基因高流动的假设。此外，绵羊和山羊的弯齿鼠种群之间没有明显的遗传分化，这与两种不同寄主之间自由共享弯齿鼠种群是一致的。总的来说，我们认为这些结果首次提供了明确的遗传证据，证明一种驱虫抗性突变是从单一来源传播到多个不同地点的。(C) 2015年Elsevier Ltd.代表Australian Society for Parasitology Inc出版。
It is important to understand how anthelmintic drug resistance mutations arise and spread in order to determine appropriate mitigation strategies. We hypothesised that a molecular genetic study of Haemonchus contortus in southern India, a region where resistance may be less advanced than in western Europe and North America, might provide some important insights into the origin and spread of anthelmintic resistance. The F200Y (T (A) under barC) isotype-1 beta-tubulin benzimidazole resistance mutation is common in H. contortus throughout the world and the F167Y (T (A) under barC) and E198A (G (C) under barA) mutations, although less common, have been reported in a number of different countries. We have investigated the haplotypic diversity and phylogenetic relationship of isotype-1 beta-tubulin benzimidazole resistance alleles for 23 H. contortus populations from small ruminants across southern India. The F200Y (T (A) under barC) mutation was most common, being detected in 18123 populations at frequencies between 9% and 84% and the E198A (G (C) under barA) mutation was also detected in 8/23 populations at frequencies between 8% and 18%. The F167Y (T (C) under barC) mutation was not detected in any of the 23 populations. Phylogenetic haplotype network analysis suggested that the F200Y (T (A) under barC) mutation has arisen multiple independent times in the region with at least three independent origins of resistance alleles across the populations surveyed. In contrast, the E198A (G (C) under barA) mutation was present on a single haplotype which, given the high level of haplotypic diversity of the susceptible alleles in the region, suggests this particular mutation has spread from a single origin, likely by anthropogenic animal movement. Population genetic analysis of 12 of the H. contortus populations, using a panel of eight microsatellite markers, revealed extremely low genetic differentiation between populations, consistent with the hypothesis of high gene flow among sites. Additionally, there was no significant genetic differentiation between H. contortus taken from sheep and goats which is consistent with H. contortus populations being freely shared between these two different hosts. Overall, we believe these results provide the first clear genetic evidence for the spread of an anthelmintic resistance mutation to multiple different locations from a single origin. (C) 2015 Published by Elsevier Ltd. on behalf of Australian Society for Parasitology Inc.