Genome-Wide Association Analysis of Anoxia Tolerance in Drosophila melanogaster
Genome-Wide Association Analysis of Anoxia Tolerance in Drosophila melanogaster
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DOI：
10.1534/g3.119.400421
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发表时间：
2019-09-01
影响因子：
2.6
通讯作者：
Harrison, Jon F.
中科院分区：
文献类型：
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作者：
Campbell, Jacob B.;Overby, Paula F.;Harrison, Jon F.
由于缺氧耐受性变异的遗传基础知之甚少，我们使用果蝇遗传学参考小组（DGRP）进行全基因组关联研究（GWAS）的成年和幼虫果蝇的缺氧耐受性。存活率范围为0-100%的成人暴露于6小时的缺氧和20-98%的幼虫暴露于1小时的缺氧。耐缺氧能力的广义遗传力为0.552，幼虫为0.433。幼虫和成人的表型弱相关，但成年男性和女性的耐缺氧性强相关。GWA在成虫中鉴定出180个SNPs，在幼虫中鉴定出32个SNPs与缺氧耐受性相关。基因本体富集分析表明，119个多态性基因与成人耐缺氧相关的离子转运或免疫功能。与此相反，22个与幼虫耐缺氧相关的多态性基因大多与转录和DNA复制调控有关。定位基因的RNAi通常支持这些基因的破坏降低缺氧耐受性的假设。对于两个离子转运基因，我们测试了SNP等位基因对成人缺氧耐受性的预测方向和性别特异性影响，并在一种情况下找到了强有力的支持，但另一种情况下没有。将我们的表型与先前的DGRP研究相关联表明，影响缺氧耐受性的基因也影响抗应激性、免疫功能和离子平衡。总的来说，我们的研究结果提供了证据，多个新的潜在的遗传影响缺氧耐受性和离子平衡和免疫过程中的重要作用，在确定缺氧耐受性的变化提供了额外的支持。
As the genetic bases to variation in anoxia tolerance are poorly understood, we used the Drosophila Genetics Reference Panel (DGRP) to conduct a genome-wide association study (GWAS) of anoxia tolerance in adult and larval Drosophila melanogaster. Survival ranged from 0-100% in adults exposed to 6 h of anoxia and from 20-98% for larvae exposed to 1 h of anoxia. Anoxia tolerance had a broad-sense heritability of 0.552 in adults and 0.433 in larvae. Larval and adult phenotypes were weakly correlated but the anoxia tolerance of adult males and females were strongly correlated. The GWA identified 180 SNPs in adults and 32 SNPs in larvae associated with anoxia tolerance. Gene ontology enrichment analysis indicated that many of the 119 polymorphic genes associated with adult anoxia-tolerance were associated with ionic transport or immune function. In contrast, the 22 polymorphic genes associated with larval anoxia-tolerance were mostly associated with regulation of transcription and DNA replication. RNAi of mapped genes generally supported the hypothesis that disruption of these genes reduces anoxia tolerance. For two ion transport genes, we tested predicted directional and sex-specific effects of SNP alleles on adult anoxia tolerance and found strong support in one case but not the other. Correlating our phenotype to prior DGRP studies suggests that genes affecting anoxia tolerance also influence stress-resistance, immune function and ionic balance. Overall, our results provide evidence for multiple new potential genetic influences on anoxia tolerance and provide additional support for important roles of ion balance and immune processes in determining variation in anoxia tolerance.