Genetic diversity estimates for the Caenorhabditis Intervention Testing Program screening panel.
Genetic diversity estimates for the Caenorhabditis Intervention Testing Program screening panel.
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DOI：
10.17912/micropub.biology.000518
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发表时间：
2022
影响因子：
--
通讯作者：
Phillips PC
中科院分区：
文献类型：
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作者：
Teterina AA;Coleman-Hulbert AL;Banse SA;Willis JH;Perez VI;Lithgow GJ;Driscoll M;Phillips PC
小杆线虫干预测试计划（CITP）的建立原则是，在遗传多样性测试集上具有积极作用的化合物应具有增加的参与具有哺乳动物翻译潜力的保守生物化学途径的可能性。为了完成其任务，CITP使用小杆线虫菌株的遗传多样性小组来测定候选化合物的长寿效应。该小组包括来自三个不同物种的22个菌株，在全球范围内收集，以实现种群间的遗传多样性。这三个代表种，C. elegans、秀丽隐杆线虫C. briggsae，和C. tropicalis，都是连续雌雄同体，这简化了实验程序，同时最大限度地提高种群内的同质性。在这里，我们提出了基于其最近发表的和公开可用的全基因组序列以及两个新生成的基因组数据集的面板中的组成菌株封装的遗传多样性的估计。我们观察到C. elegans（1.2e-3），C. briggsae（7.5e-3）和C. tropicalis菌株（2.6e-3）高于人类种群的估计值，与小鼠种群中发现的相似。我们的分析支持CITP筛选小组包含广泛的遗传多样性的假设，这表明在整个小组中具有功效的延长寿命的化学物质应该被富集用于在遗传背景中共享的保守过程上发挥作用的干预措施。虽然多样性小组是由CITP为研究长寿干预措施而建立的，但该小组在为具有潜在遗传背景效应的任何表型寻求广泛有效的干预措施时，可能对更广泛的研究界有用。
The Caenorhabditis Intervention Testing Program (CITP) was founded on the principle that compounds with positive effects across a genetically diverse test-set should have an increased probability of engaging conserved biochemical pathways with mammalian translational potential. To fulfill its mandate, the CITP uses a genetic diversity panel of Caenorhabditis strains for assaying longevity effects of candidate compounds. The panel comprises 22 strains from three different species, collected globally, to achieve inter-population genetic diversity. The three represented species, C. elegans, C. briggsae, and C. tropicalis, are all sequential hermaphrodites, which simplifies experimental procedures while maximizing intra-population homogeneity. Here, we present estimates of the genetic diversity encapsulated by the constituent strains in the panel based on their most recently published and publicly available whole-genome sequences, as well as two newly generated genomic data sets. We observed average genome-wide nucleotide diversity (π) within the C. elegans (1.2e-3), C. briggsae (7.5e-3), and C. tropicalis strains (2.6e-3) greater than estimates for human populations, and comparable to that found in mouse populations. Our analysis supports the assumption that the CITP screening panel encompasses broad genetic diversity, suggesting that lifespan-extending chemicals with efficacy across the panel should be enriched for interventions that function on conserved processes that are shared across genetic backgrounds. While the diversity panel was established by the CITP for studying longevity interventions, the panel may prove useful for the broader research community when seeking broadly efficacious interventions for any phenotype with potential genetic background effects.