molecular basis 2

Molecular basis of phenotypic variation and adaptation

A central goal of research in the Chakraborty lab is understanding the genomic and molecular basis of phenotypic variation and adaptation. While most changes in a trait affecting organismal fitness are considered deleterious, many 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). Our present focus is on mutations caused by large (>100 bp) changes in genome structure (e.g., duplication, deletion, transposition, inversion of sequences), collectively known as structural variants or SVs. Although SVs cause diseases and drive adaptations, short reads miss many genome-wide SVs, obscuring candidate mutations for phenotypic variation and adaptation. We employ cutting-edge methods in genomics, genome editing, and population and quantitative genetics to decipher the functional and evolutionary consequences of SVs at the molecular, cellular, and organismal levels. We use the model organism Drosophila melanogaster and the invasive malaria vector Anopheles stephensi) for our research, but we are extending our work to other organisms.

repeats feature

Repetitive genome, sexual conflict, and the evolution of sexual dimorphism

Although males and females of a species share the same genome more or less, they exhibit different adaptive optima for many traits. The resulting sexually antagonistic selection and sexual conflict lead to the 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.

constraint 1

Protein structural constraints, maintenance of genetic variation, and evolution of new genes

Fundamental molecular properties that promote the maintenance of heritable phenotypic variation and functional innovation are largely unknown. Structural constraints in a protein can hinder optimizing its 3D structure simultaneously for multiple functions if each function requires a different optimal structure. Promiscuous enzymes are prone to such constraints because their substrates for different functions may bind optimally to different structures of the enzyme. Any amino acid changes in the enzyme that improves the structure for function may compromise another function. Such constraints can prevent the spreading of a beneficial amino acid variant and facilitate the origin of new genes and the diversification of protein families. Our lab uses molecular evolution theory, protein mutagenesis and functional assays, transgenics, and fitness assays to elucidate the roles protein structural constraints play in maintaining phenotypic variation by balancing natural selection and the evolution of new genes and gene families.