Biology subjects

Harrison, R. G.

Publications and source records attributed to Harrison, R. G..

3 recordsLinked to original sources

bioRxiv2021

Consequences of coupled barriers to gene flow for the build-up of genomic differentiation

Theory predicts that when different barriers to gene flow become coincident, their joint effects enhance reproductive isolation and genomic divergence beyond their individual effects, but empirical tests of this coupling hypothesis are rare. Here, we analyze patterns of gene exchange among populations of European corn borer moths that vary in the number of acting barriers, allowing for comparisons of genomic variation when barrier traits or loci are in coincident or independent states. We find that divergence is mainly restricted to barrier loci when populations differ by a single barrier, whereas the coincidence of temporal and behavioral barriers is associated with divergence of two chromosomes harboring barrier loci. Furthermore, differentiation at temporal barrier loci increases in the presence of behavioral divergence and differentiation at behavioral barrier loci increases in the presence of temporal divergence. Our results demonstrate how the joint action of coincident barrier effects leads to levels of genomic differentiation that far exceed those of single barriers acting alone, consistent with theory arguing that coupling allows indirect selection to combine with direct selection and thereby lead to a stronger overall barrier to gene flow. Thus, the state of barriers - independent or coupled - strongly influences the accumulation of genomic differentiation.

evolutionary biology↗

bioRxiv2020

Mechanism and kinetics of copper complexes binding to the influenza A M2 channel

Copper(II) is known to bind in the influenza virus His37 cluster in the homotetrameric M2 proton channel and block the proton current needed for uncoating. Copper complexes based on iminodiacetate also block the M2 proton channel and show reduced cytotoxicity and zebrafish-embryo toxicity. In voltage-clamp oocyte studies using the ubiquitous amantadine-insensitive M2 S31N variant, the current block showed fast and slow phases in contrast to the single phase found for amantadine block of WT M2. Here we evaluate the mechanism of block by copper adamantyl iminodiacitate (Cu(AMT-IDA)) and copper cyclooctyl iminodiacitate (Cu(CO-IDA)) complexes and address whether the complexes can covalently bind to one or more of the His37 imidazoles. The current traces were fitted to parametrized master equations. The energetics of binding and the rate constants suggest that the first step is copper-complex binding within the channel and the slow step in the current block is the covalent bond formation between copper complex and histidine. Isothermal titration calorimetry (ITC) indicates that a single imidazole binds strongly to the copper complexes. Structural optimization using density functional theory (DFT) reveals that the complexes fit inside the channel and project the Cu(II) towards the His37 cluster allowing one imidazole to form a covalent bond with the Cu(II). Electrophysiology and DFT studies also show that the complexes block the G34E amantadine-resistant mutant in spite of some crowding in the binding site by the glutamates.

biophysics↗

bioRxiv2019

Genomic basis of circannual rhythm in the European corn borer moth

Genetic variation in life-history timing allows populations to synchronize with seasonal cycles but little is known about the molecular mechanisms that produce differences in circannual rhythm in nature. Changes in diapause timing in the European corn borer moth (Ostrinia nubilalis) have facilitated rapid response to shifts in winter length encountered during range expansion and from climate change, with some populations emerging from diapause earlier to produce an additional generation per year. We identify genomic variation associated with changes in the time spent in winter diapause and show evidence that the circadian clock genes period (per) and pigment dispersing factor receptor (Pdfr) interact to underlie this adaptive polymorphism in circannual rhythm. Per and Pdfr are located within two epistatic QTL, strongly differ in allele frequency among individuals that pupate earlier or later, have the highest linkage disequilibrium among gene pairs in the QTL regions despite separation by > 4 megabases, and possess amino-acid changes likely to affect function. One per mutation in linkage disequilibrium with Pdfr creates a novel putative clock-cycle binding site found exclusively in populations that pupate later. We find associated changes in free-running daily circadian rhythm, with longer daily rhythms in individuals that end diapause early. These results support a modular connection between circadian and circannual timers and provide testable hypotheses about the physiological role of the circadian clock in seasonal synchrony. Winter length is expected to continually shorten from climate warming and we predict these gene candidates will be targets of selection for future adaptation and population persistence.

evolutionary biology↗