Mechanisms of chromosomal plasticity in malaria mosquitoes

Mosquitoes, along with Drosophila, are model organisms for studying rearrangements of the genome, which invert chromosome segments by 180 degrees. Mosquitoes of the Maculipennis group include species with many polymorphic chromosomal inversions and species with no or very few polymorphic inversions. Mosquito species with the high level of inversion polymorphism have the widest geographic distribution and a remarkable ability to adapt to different climate conditions from warm environments to cold climatic zones in Eurasia and North America. Also, five chromosomal arms of mosquitoes remarkably differ in rates of inversion polymorphism and fixation. However, the specific roles of inversions in species adaptation as well as mechanisms of their origin and function are poorly understood.

The proposed project will address the problem of origin and functional significance of chromosomal inversions by studying genomes and transcriptomes of species from the Maculipennis group. The investigators will test the hypothesis that interactions within the genome play the central role in the generation of rearrangements. The researchers will apply the innovative Hi-C approach to identify both short-range chromatin interactions defined as topologically associating domains (TADs) and long-range interactions—megabases-long chromosome loops. Their preliminary data demonstrate that the genomic distribution of repetitive DNA together with long-range chromatin interactions may explain the species- and chromosome-specific patterns of chromosomal rearrangements. TADs have also been shown to be important for gene regulation by restricting to some degree the interaction of cell-type specific enhancers with their target genes. The research team suggests that the breakpoints of inversions are located within TADs, the rearrangement of which can lead to a change in the gene expression profile. Thus, chromosomal inversions can be the main factor in the reorganization of TADs in evolution. Moreover, the investigators hypothesize that genes located within the polymorphic inversions are differentially expressed in the alternative arrangements. As a result, this evolutionary approach will help to understand the rules governing genetic functions.

The “inversion origin” and “inversion effect” hypotheses will be tested by analyzing chromosomally polymorphic (An. messeae and An. beklemishevi) and chromosomally monomorphic (An. atroparvus and An. freeborni) species. To successfully achieve the research goal, the investigators will develop chromosome-level genome assemblies for An. messeae, An. beklemishevi, and An. freeborni, as they have already done for An. atroparvus.

The role of chromatin organization in evolutionary rearrangements in insect species will be tested for the first time in the proposed project. The research aims will be accomplished by using innovative approaches and methods. For the first time, the team will be using Oxford Nanopore sequencing technology to obtain high-quality genome assemblies for mosquitoes. An innovative Hi-C approach will be used to scaffold genomic contigs to the chromosome level and to identify TADs and long-range chromatin interactions in mosquitoes. The investigators will use multicolor FISH to map the Oxford Nanopore assembly to polytene chromosomes using an efficient protocol. The research team is uniquely qualified to perform the proposed project. The high quality of the expected results is confirmed by the professionalism of the team members involved in the project and their multiple publications in Science, Nature, PNAS, and other journals on topics of direct relevance to this project.

Project details

Basic Science
Enabling Technologies & Assays
Genetics and Genomics

Jan 2021 — Dec 2023

Russian Federation