Molecular basis of phenotypic variation and adaptation

A central goal of research in the Chakraborty lab is to understand the genomic and molecular basis of phenotypic variation and adaptation.  While most changes in a trait affecting organismal fitness are considered deleterious (e.g. disease causing mutations), some are adaptive. Our lab is interested in understanding the molecular properties, functional effects, and evolutionary dynamics of the mutations that cause variation in complex traits (i.e. traits with complex genetic basis). We are particularly interested in mutations caused by large (>100 bp) changes in genome structure (e.g.  duplication, deletion, transposition, inversion of sequences), which are collectively known as structural variants or SVs. Although SVs cause human diseases and drive adaptations, technical limitations impeded discovery and in-depth analysis of genome-wide SVs, obscuring a sizable proportion of genetic variation that exerts large effects on fitness. To solve the challenges in understanding the evolutionary and functional consequences of SVs, Chakraborty lab employs cutting edge methods in quantitative and population genetics, genomics, and genome editing . Our lab uses both model organisms (e.g. Drosophila melanogaster) and non-model organisms (e.g. invasive malaria vector Anopheles stephensi) for research.

Role of repetitive genome in evolution of sexual dimorphism and sexual conflict

Despite sharing much of the same genome, males and females of a species exhibit different adaptive optima for many traits. The resulting sexually antagonistic selection and sexual conflict leads to evolution of sexually dimorphic phenotypes at both organismal and molecular levels. The Y chromosome in Diptera (e.g. flies and mosquitoes) and W chromosome in Lepidoptera (butterflies and moths) only occur in males and females, respectively, creating a potential reservoir for genetic elements that would exert unequal functional and fitness effects in the two sexes. However, due to the highly repetitive, heterochromatic nature of these chromosomes, their structure and function have been recalcitrant to scrutiny. Using comparative genomics, functional genomics, and genome editing our lab investigates the roles repetitive sequences play in sexual dimorphism and sexual conflict in insects and butterflies.

1. Samano, A, Kumar, N, Liao, Y, Ishtiaq, F, Chakraborty, M. Genome structural variants shape adaptive success of an invasive urban malaria vector Anopheles stephensi. bioRxiv. 2024; :. doi: 10.1101/2024.07.29.605641. PubMed PMID:39211149 PubMed Central PMC11360885.
2. Shukla, HG, Chakraborty, M, Emerson, JJ. Genetic variation in recalcitrant repetitive regions of the Drosophila melanogaster genome. bioRxiv. 2024; :. doi: 10.1101/2024.06.11.598575. PubMed PMID:38915508 PubMed Central PMC11195212.
3. Chakraborty, M, Lara, AG, Dang, A, McCulloch, KJ, Rainbow, D, Carter, D et al.. Sex-linked gene traffic underlies the acquisition of sexually dimorphic UV color vision in Heliconius butterflies. Proc Natl Acad Sci U S A. 2023;120 (33):e2301411120. doi: 10.1073/pnas.2301411120. PubMed PMID:37552755 PubMed Central PMC10438391.
4. Chakraborty, M, Ramaiah, A, Adolfi, A, Halas, P, Kaduskar, B, Ngo, LT et al.. Author Correction: Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly. BMC Biol. 2022;20 (1):96. doi: 10.1186/s12915-022-01314-2. PubMed PMID:35501892 PubMed Central PMC9059397.
5. Thakare, A, Ghosh, C, Alalamath, T, Kumar, N, Narang, H, Whadgar, S et al.. The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity. Sci Rep. 2022;12 (1):3610. doi: 10.1038/s41598-022-07462-3. PubMed PMID:35246568 PubMed Central PMC8897464.
6. Durkin, SM, Chakraborty, M, Abrieux, A, Lewald, KM, Gadau, A, Svetec, N et al.. Behavioral and Genomic Sensory Adaptations Underlying the Pest Activity of Drosophila suzukii. Mol Biol Evol. 2021;38 (6):2532-2546. doi: 10.1093/molbev/msab048. PubMed PMID:33586767 PubMed Central PMC8136512.
7. Chakraborty, M, Ramaiah, A, Adolfi, A, Halas, P, Kaduskar, B, Ngo, LT et al.. Hidden genomic features of an invasive malaria vector, Anopheles stephensi, revealed by a chromosome-level genome assembly. BMC Biol. 2021;19 (1):28. doi: 10.1186/s12915-021-00963-z. PubMed PMID:33568145 PubMed Central PMC7876825.
8. Liao, Y, Zhang, X, Chakraborty, M, Emerson, JJ. Topologically associating domains and their role in the evolution of genome structure and function in Drosophila. Genome Res. 2021;31 (3):397-410. doi: 10.1101/gr.266130.120. PubMed PMID:33563719 PubMed Central PMC7919452.
9. Chakraborty, M, Chang, CH, Khost, DE, Vedanayagam, J, Adrion, JR, Liao, Y et al.. Evolution of genome structure in the Drosophila simulans species complex. Genome Res. 2021;31 (3):380-396. doi: 10.1101/gr.263442.120. PubMed PMID:33563718 PubMed Central PMC7919458.
10. Linder, RA, Majumder, A, Chakraborty, M, Long, A. Two Synthetic 18-Way Outcrossed Populations of Diploid Budding Yeast with Utility for Complex Trait Dissection. Genetics. 2020;215 (2):323-342. doi: 10.1534/genetics.120.303202. PubMed PMID:32241804 PubMed Central PMC7268983.