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通过等位基因特异性表达揭示的转录调控机制。

Mechanisms of transcriptional regulation in revealed by allele-specific expression.

机构信息

Department of Vector Biology, Liverpool School of Tropical Medicine, Pembroke Place , Liverpool L3 5QA, UK.

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SA, UK.

出版信息

Proc Biol Sci. 2024 Sep;291(2031):20241142. doi: 10.1098/rspb.2024.1142. Epub 2024 Sep 18.

Abstract

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in , by regulatory sequences on the same chromosome, and by acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in -regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb-resistant and susceptible strains to identify -regulated genes that might be responsible for the resistant phenotype using RNAseq, and CRM sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele-specific expression (ASE) in hybrids of insecticide susceptible and resistant strains, suggesting -regulation is an important mechanism of gene expression regulation in . The genes showing ASE included a higher proportion of -specific genes on average younger than genes with balanced allelic expression.

摘要

疟疾控制依赖于针对蚊子媒介的杀虫剂,但这越来越受到杀虫剂抗性的影响,这种抗性可以通过解毒酶的表达升高来实现,解毒酶可以代谢杀虫剂。在二倍体生物中,基因表达既受同一染色体上的调控序列调控,也受顺式作用因子调控,平等地影响两个等位基因。转录水平的不同可以由 -调控模块 (CRM)中的突变引起,但在蚊子中很少有这样的突变被鉴定出来。我们将苯氧威抗性和敏感 品系杂交,使用 RNAseq 鉴定可能导致抗性表型的 -调控基因,并使用机器学习预测控制与杀虫剂抗性相关组织中基因表达的 CRM 序列。我们发现 115 个基因在杀虫剂敏感和抗性品系的杂种中表现出等位基因特异性表达 (ASE),表明 -调控是基因表达调控的一个重要机制。表现出 ASE 的基因包括平均比具有平衡等位基因表达的基因更年轻的 -特异性基因的比例更高。

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