PTC2 region genotypes counteract Biomphalaria glabrata population differences between M-line and BS90 in resistance to infection by Schistosoma mansoni.

PTC2 region genotypes counteract Biomphalaria glabrata population differences between M-line and BS90 in resistance to infection by Schistosoma mansoni.
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DOI:
10.7717/peerj.13971
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发表时间:
2022
期刊:
影响因子:
2.7
通讯作者:
Tennessen, Jacob A.
Tennessen, Jacob A.
中科院分区:
生物学3区
文献类型:
--
作者:
Blouin, Michael S.;Bollmann, Stephanie R.;Tennessen, Jacob A.

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光滑生物线虫是曼氏血吸虫的钉螺中间宿主,曼氏血吸虫是人类血吸虫病的致病吸虫。BS90是研究最多的光滑芽孢杆菌菌株之一,因为它对大多数曼氏杆菌菌株都有很高的抵抗力。1999年的一项F2作图研究发现了两个与BS90群体相对于敏感M系群体显性抗性的单基因座相关的随机扩增多态性标记。一个标记不能被定位,但另一个标记OPM-04映射到PTC2的5Mb以内,我们最近显示的一个区域对受到相同寄生虫株(PR1)挑战的另一个钉螺种群的抵抗力有非常大的影响。在这里,我们检验了PTC2区域包含因果基因/S的假设,该基因解释了BS90钉螺的标志性抗性。利用分子标记辅助回交的方法,将PtC2区的BS90型(两侧+/−~1Mb)导入M线(易感品系)遗传背景,将M线突变带入BS90型遗传背景。我们用PR1株血吸虫攻击后代,并在共同的遗传背景下测试PTC2区域的等位基因变异的影响。相对于M线单倍型,BS90单倍型实际上增强了易感性。因此,我们拒绝接受我们最初的假设。对我们的结果的一种可能的解释是,与OPM-04相关的因果基因很近,但不在我们导入每一条线的PTC2块中。因此,我们使用F2杂交在随机遗传背景下独立测试PTC2和OPM-04区域的影响。我们证实,BS90单倍型增加了易感性,我们在OPM-04上看到了类似的影响,尽管不显著。我们讨论了我们的结果与1999年的研究结果如此显著不同的可能原因。我们还介绍了BS90和M-line中PTC2及其侧翼区的PacBio组装,与以前发表的PTC2单倍型进行了比较,并讨论了可能导致BS90单倍型易感性增强的候选基因。
Biomphalaria glabrata is a snail intermediate host for Schistosoma mansoni, a trematode responsible for human schistosomiasis. BS90 is one of the most well studied strains of B. glabrata owing to its high resistance to infection by most strains of S. mansoni. An F2 mapping study from 1999 identified two RAPD markers that associated with what appeared to be single-locus, dominant resistance by the BS90 population relative to the susceptible M-line population. One marker cannot be mapped, but the other, OPM-04, maps to within 5 Mb of PTC2, a region we recently showed has a very large effect on resistance within another snail population challenged by the same strain of parasite (PR1). Here we tested the hypothesis that the PTC2 region contains the causal gene/s that explain the iconic resistance of BS90 snails. We used marker-assisted backcrossing to drive the BS90 version of the PTC2 region (+/−~1 Mb on either side) into an M-line (susceptible strain) genetic background, and the M-line version into a BS90 genetic background. We challenged the offspring with PR1-strain schistosomes and tested for effects of allelic variation in the PTC2 region in a common genetic background. Relative to M-line haplotypes, the BS90 haplotype actually confers enhanced susceptibility. So we reject our original hypothesis. One possible explanation for our result was that the causal gene linked to OPM-04 is near, but not in the PTC2 block that we introgressed into each line. So we used an F2 cross to independently test the effects of the PTC2 and OPM-04 regions in a randomized genetic background. We confirmed that the BS90 haplotype confers increased susceptibility, and we see a similar, although non-significant effect at OPM-04. We discuss possible reasons why our results differed so dramatically from those of the 1999 study. We also present Pacbio assemblies of the PTC2 and flanking region in BS90 and M-line, compare with previously published PTC2 haplotypes, and discuss candidate genes that might be behind the enhanced susceptibility of the BS90 haplotype.
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