Buck Institute for Research on Aging, Novato, CA, United States.
Department of Plant and Microbial Biology, UC Berkeley, Berkeley, CA, United States.
BMC Genomics. 2022 Dec 20;23(1):842. doi: 10.1186/s12864-022-09063-w.
Organisms in the wild can acquire disease- and stress-resistance traits that outstrip the programs endogenous to humans. Finding the molecular basis of such natural resistance characters is a key goal of evolutionary genetics. Standard statistical-genetic methods toward this end can perform poorly in organismal systems that lack high rates of meiotic recombination, like Caenorhabditis worms.
Here we discovered unique ER stress resistance in a wild Kenyan C. elegans isolate, which in inter-strain crosses was passed by hermaphrodite mothers to hybrid offspring. We developed an unbiased version of the reciprocal hemizygosity test, RH-seq, to explore the genetics of this parent-of-origin-dependent phenotype. Among top-scoring gene candidates from a partial-coverage RH-seq screen, we focused on the neuronally-expressed, cuticlin-like gene cutl-24 for validation. In gene-disruption and controlled crossing experiments, we found that cutl-24 was required in Kenyan hermaphrodite mothers for ER stress tolerance in their inter-strain hybrid offspring; cutl-24 was also a contributor to the trait in purebred backgrounds.
These data establish the Kenyan strain allele of cutl-24 as a determinant of a natural stress-resistant state, and they set a precedent for the dissection of natural trait diversity in invertebrate animals without the need for a panel of meiotic recombinants.
野生生物可以获得超越人类内在程序的疾病和压力抗性特征。找到这种自然抗性特征的分子基础是进化遗传学的一个关键目标。对于缺乏高减数分裂重组率的生物系统，如秀丽隐杆线虫，标准的统计遗传方法往往效果不佳。
在这里，我们在肯尼亚野生秀丽隐杆线虫分离株中发现了独特的 ER 应激抗性，在种间杂交中，这种抗性通过雌雄同体的母亲传递给杂交后代。我们开发了一种无偏的正反交半合子测试（RH-seq）版本，以探索这种母源依赖表型的遗传基础。在部分覆盖 RH-seq 筛选的顶级基因候选者中，我们专注于神经元表达的、类角质素样基因 cutl-24 进行验证。在基因敲除和受控杂交实验中，我们发现 cutl-24 是肯尼亚雌雄同体母亲在其种间杂交后代中耐受 ER 应激所必需的；cutl-24 也是纯合背景中该性状的一个贡献者。
这些数据确立了 cutl-24 的肯尼亚菌株等位基因是自然应激抗性状态的决定因素，并为在没有减数重组面板的情况下对无脊椎动物的自然性状多样性进行剖析开创了先例。
