Three-Dimensional Genome Organization in Mosquito Brains: An Analysis of Anopheles coluzzii and Culex quinquefasciatus Using Micro-C

Abstract

Studies of genome organization in Drosophila melanogaster have revealed that physical interactions between DNA loci influence gene expression. Recently, ultra-long interactions between loci megabases apart have been discovered, defined as meta-loops. Notably, genes brought into proximity by these meta-loops are enriched for those involved in axon guidance and synapse formation, suggesting a role in shaping Drosophila behavior. Building on these insights, studying genome organization in mosquitoes may help uncover genetic mechanisms underlying behaviors relevant to vector-borne disease transmission. This project aimed to characterize the three-dimensional genome organization in Anopheles coluzzii and Culex quinquefasciatus mosquitoes through Micro-C chromosome conformation capture technology. This technique enabled the creation of high-resolution maps that revealed both local and broad-scale chromatin architecture. Analysis of genes near Anopheles meta-loops revealed enrichment of gene ontology terms related to neural development, consistent with findings in Drosophila. Comparisons of chromatin structure across sexes showed minimal differences, suggesting that sex-specific gene expression may rely on other regulatory mechanisms. Comparisons between the Anopheles brain and gonads revealed notable variation in chromatin structure, implicating both local and long-range interactions in tissue-specific gene expression. Together, these findings highlight the possible regulatory role of genome organization in mosquitoes, which may be leveraged to address the global burden of vector-borne disease.