LAUSR

Simple Summary In eukaryotes, the fraction of the genome not coding for proteins vastly outsizes the portion containing protein-coding genes. This non-coding genome, once termed “junk”, was thought for decades to be inconsequential to the biology of an organism. It is now widely acknowledged that elements within the non-coding genome serve important gene-regulatory functions impacting when, where, and to what levels genes and their protein products are expressed. Without an amino acid-like code to decipher non-coding regulatory elements within the genome, significant technology development has aided in their discovery. Currently, genome-wide identification of non-coding regulatory elements is an active area of research with significant progress made in humans, mice, and other model organisms. However, work to address the roles of these elements in mosquito disease vectors is in its infancy. In this article, we review existing methodology to generate genome-wide catalogs for three classes of non-coding elements and discuss their use in mosquito disease vectors and other insects. Abstract The portion of the mosquito genome that does not code for proteins contains regulatory elements that likely underlie variation for important phenotypes including resistance and susceptibility to infection with arboviruses and Apicomplexan parasites. Filtering the non-coding genome to uncover these functional elements is an expanding area of research, though identification of non-coding regulatory elements is challenging due to the lack of an amino acid-like code for the non-coding genome and a lack of sequence conservation across species. This review focuses on three types of non-coding regulatory elements: (1) microRNAs (miRNAs), (2) long non-coding RNAs (lncRNAs), and (3) enhancers, and summarizes current advances in technical and analytical approaches for measurement of each of these elements on a genome-wide scale. The review also summarizes and highlights novel findings following application of these techniques in mosquito-borne disease research. Looking beyond the protein-coding genome is essential for understanding the complexities that underlie differential gene expression in response to arboviral or parasite infection in mosquito disease vectors. A comprehensive understanding of the regulation of gene and protein expression will inform transgenic and other vector control methods rooted in naturally segregating genetic variation.