Biology subjects

Harris, M. E.

Publications and source records attributed to Harris, M. E..

3 recordsLinked to original sources

bioRxiv2025

Divergent climate impacts despite similar response to temperature in a widespread aerial insectivore

Climate change is shifting when animals breed1,2, but it is still not clear why some populations keep pace with warming while others fall behind3,4. Differences could arise from variation in sensitivity to temperature3 or constraints on the ability to respond to temperature. Without knowing whether populations differ in sensitivity--or in their ability to act on that sensitivity--we cannot identify which are most at risk. Using 1,555 population-years from 123 populations of tree swallows (Tachycineta bicolor), we show that populations have similar sensitivity to local temperature, advancing breeding by about one day per degree of warming. However, northern populations face tighter time constraints and greater exposure to recent warming. Northern populations have advanced laying dates the most, but still experience stronger selection for earlier breeding, especially in warm years; they have also declined most in breeding abundance. These findings show that vulnerability to climate change can arise not just from different sensitivity to warming, but from when and where populations can respond effectively. By disentangling sensitivity from timing constraints, our results support a general mechanism by which even uniformly responsive species can show uneven impacts of climate change across their ranges.

ecology↗

bioRxiv2019

Benzoate-Tolerant Escherichia coli Strains from Experimental Evolution Lose the Gad Regulon, Multi-Drug Efflux Pumps, and Hydrogenases

Benzoate, a partial uncoupler of the proton motive force (PMF), selects for sensitivity to chloramphenicol and tetracycline in Escherichia coli K-12. Genetic mechanisms of increased benzoate tolerance and decreased drug resistance were analyzed in strains isolated from experimental evolution with benzoate. Transcriptomes showed reversal of benzoate-dependent regulation, including the Gad regulon for acid resistance and multi-drug resistance (MDR). Benzoate-evolved strains knocked down the nitrate reductase narHJ and the acid-consuming hydrogenase Hyd-3, but upregulated OmpF and other porins that admit nutrients and antibiotics. Mutations were found affecting many genes of aromatic catabolism such as folD and add. Several candidate genes from benzoate-evolved strains had a role in benzoate tolerance. Growth with benzoate or salicylate was increased by deletion of the Gad activator ariR, or by deletion of the slp-gadX acid fitness island encoding Gad regulators and the MDR pump MdtEF. Benzoate growth was also increased by deletion of MDR component emrA, the RpoS post-transcriptional regulator cspC, or the adenosine deaminase add. Growth in chloramphenicol with benzoate was decreased by a point mutation in the RNA polymerase alpha-subunit rpoA, which appeared in one chloramphenicol-sensitive benzoate-evolved strain. Growth in chloramphenicol was also decreased by deletion of Mar activator rob, or of rfaY (lipopolysaccharide biosynthesis). Hydrogenase Hyd-3 deletion increased benzoate tolerance. Overall, long-term culture in the presence of benzoate or salicylate favors loss of MDR efflux pumps and of hydrogenases that generate a futile cycle of PMF; and favors upregulation of large-hole porins that increase uptake of fermentable nutrients and of antibiotics. IMPORTANCEBenzoate is a common food preservative, and salicylate is the active form of aspirin. In E. coli, benzoate derivatives upregulate multiple regulons that export antibiotics and other toxic products, and downregulate large outer-membrane porins that allow antibiotic influx. But benzoate or salicylate exposure causes energy stress by depleting the proton motive force. In the absence of antibiotics, long-term benzoate exposure selects against energy-spending systems such as multi-drug efflux pumps and the proton-consuming hydrogenase. Selection favors upregulation of porins that admit fermentable substrates but also allow entry of antibiotics. Thus, evolution with benzoate requires a tradeoff for antibiotic sensitivity. Benzoate and salicylate are naturally occurring plant signal molecules that may influence the evolution of microbiomes in plants and in animal digestive tracts. Effects on hydrogenase activity may be relevant to the biotechnology of hydrogen production.

microbiology↗

bioRxiv2017

Modeling of Epigenetic Modification-Induced Changes in CRX-dependent Genes cis-Regulatory Elements

PurposeDNA methylation is a well characterized epigenetic repressor of mRNA transcription in many plant and vertebrate systems. However, the mechanism of this repression is not fully understood. The process of synthesizing a strand of RNA from DNA, or transcription, is controlled by proteins that regulate RNA polymerase activity by binding to specific gene regulatory sequences. Cone-rod homeobox (CRX) is a well-characterized mammalian transcription factor that controls photoreceptor cell specific gene expression. While much is known about the functions and DNA binding specificity of CRX, less is known about how DNA methylation modulates CRX binding affinity to genomic cis-regulatory elements.\n\nMethodsWe used bisulfite pyrosequencing of human ocular tissues to measure DNA methylation levels of the regulatory regions of RHO, PDE6B, PAX6, and LINE. To describe the molecular mechanism of repression, we used molecular modeling to illustrate the effect of DNA methylation on human RHO regulatory sequences.\n\nResultsIn this study, we demonstrate an inverse correlation between DNA methylation in regulatory regions adjacent to the human RHO and PDE6B genes and their subsequent transcription in human ocular tissues. Docking of CRX to our DNA models shows that CRX interacts with the grooves of these sequences, suggesting changes in groove structure could regulate binding. Molecular dynamics simulations of the RHO promoter and enhancer regions show changes in the flexibility and groove width upon epigenetic modification. Models also demonstrate that changes to the local dynamics of CRX binding sites within RHO regulatory sequences which may account for the repression of CRX dependent transcription.\n\nConclusionCollectively, these data demonstrate epigenetic regulation of CRX binding sites in human retinal tissue and provide insight into the mechanism of this mode of epigenetic regulation to be tested in future experiments.

molecular biology↗