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Biology subjects

Clark, N. L.

Publications and source records attributed to Clark, N. L..

3 recordsLinked to original sources

RERconverge: an R package for associating evolutionary rates with convergent traits

Motivation: When different lineages of organisms independently adapt to similar environments, selection often acts repeatedly upon the same genes, leading to signatures of convergent evolutionary rate shifts at these genes. With the increasing availability of genome sequences for organisms displaying a variety of convergent traits, the ability to identify genes with such convergent rate signatures would enable new insights into the molecular basis of these traits.\n\nResults: Here we present the R package RERconverge, which tests for association between relative evolutionary rates of genes and the evolution of traits across a phylogeny. RERconverge can perform associations with binary and continuous traits, and it contains tools for visualization and enrichment analyses of association results.\n\nAvailability: RERconverge source code, documentation, and a detailed usage walk-through are freely available at https://github.com/nclark-lab/RERconverge. Datasets for mammals, Drosophila, and yeast are available at https://bit.ly/2J2QBnj.\n\nContact: mchikina@pitt.edu\n\nSupplementary information: Supplementary information, containing detailed vignettes for usage of RERconverge, are available at Bioinformatics online.

evolutionary biology

Evolutionary rate covariation analysis of E-cadherin identifies Raskol as regulator of cell adhesion and actin dynamics in Drosophila

The adherens junction couples the actin cytoskeletons of neighboring cells to provide the foundation for multicellular organization. The core of the adherens junction is the cadherin-catenin complex that arose early in the evolution of multicellularity to link cortical actin to intercellular adhesions. Over time, evolutionary pressures have shaped the signaling and mechanical functions of the adherens junction to meet specific developmental and physiological demands. Evolutionary rate covariation (ERC) identifies genes with correlated fluctuations in evolutionary rate that can reflect shared selective pressures and functions. Here we use ERC to identify genes with evolutionary histories similar to shotgun (shg), which encodes the Drosophila E-cadherin (DE-Cad) ortholog. Core adherens junction components -catenin and p120-catenin displayed strong ERC correlations with shg, indicating that they evolved under similar selective pressures during evolution between Drosophila species. Further analysis of the shg ERC profile revealed a collection of genes not previously associated with shg function or cadherin-mediated adhesion. We then analyzed the function of a subset of ERC-identified candidate genes by RNAi during border cell (BC) migration and identified novel genes that function to regulate DE-Cad. Among these, we found that the gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates BC migration and adhesion. We named CG42684 raskol (\"to split\" in Russian) and show that it regulates DE-Cad levels and actin protrusions in BCs. We propose that Raskol functions with DE-Cad to restrict Ras/Rho signaling and help guide BC migration. Our results demonstrate that a coordinated selective pressure has shaped the adherens junction and this can be leveraged to identify novel components of the complexes and signaling pathways that regulate cadherin-mediated adhesion.\n\nAuthor SummaryThe establishment of intercellular adhesions facilitated the genesis of multicellular organisms. The adherens junction, which links the actin cytoskeletons of neighboring cells, arose early in the evolution of multicellularity and selective pressures have shaped its function and molecular composition over time. In this study, we used evolutionary rate covariation (ERC) analysis to examine the evolutionary history of the adherens junction and to identify genes that coevolved with the adherens junction gene shotgun, which encodes the Drosophila E-cadherin (DE-Cad). ERC analysis of shotgun revealed a collection of genes with similar evolutionary histories. We then tested the role of these genes in border cell migration in the fly egg chamber, a process that requires the coordinated regulation of cell-cell adhesion and cell motility. Among these, we found that a previously uncharacterized gene CG42684, which encodes a putative GTPase activating protein (GAP), regulates the collective cell migration of border cells, stabilizes cell-cell adhesions and regulates the actin dynamics. Our results demonstrate that components of the adherens junction share an evolutionary history and that ERC analysis is a powerful method to identify novel components of cell adhesion complexes in Drosophila.

genetics

The Molecular Genetic Basis of Herbivory between Butterflies and their Host-Plants

Interactions between herbivorous insects and their host-plants are a central component of terrestrial food webs and a critical topic in agriculture, where a substantial fraction of potential crop yield is lost annually to pests. Important insights into plant-insect interactions have come from research on specific plant defenses and insect detoxification mechanisms. Yet, much remains unknown about the molecular mechanisms that mediate plant-insect interactions. Here we use multiple genome-wide approaches to map the molecular basis of herbivory from both plant and insect perspectives, focusing on butterflies and their larval host-plants. Parallel genome-wide association studies in the Cabbage White butterfly, Pieris rapae, and its host-plant, Arabidopsis thaliana, pinpointed a small number of butterfly and plant genes that influenced herbivory. These genes, along with much of the genome, were regulated in a dynamic way over the time course of the feeding interaction. Comparative analyses, including diverse butterfly/plant systems, showed a variety of genome-wide responses to herbivory, yet a core set of highly conserved genes in butterflies as well as their host-plants. These results greatly expand our understanding of the genomic causes and evolutionary consequences of ecological interactions across two of Natures most diverse taxa, butterflies and flowering plants.

genomics