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Mahesh, A.

Publications and source records attributed to Mahesh, A..

2 recordsLinked to original sources

The genomic basis of local adaptation to photoperiod across altitude in a self-fertilizing monkeyflower

Local adaptation along altitudinal gradients is well documented in many plant species, however the genetic basis of adaptive variation over these steep environmental clines remains poorly understood. Populations of Mimulus laciniatus, a self-fertilizing annual plant, experience highly differentiated seasonal environments throughout the Sierra Nevada, CA, where the length of the growing season and timing of favorable flowering conditions vary with altitude. These differences have driven divergence in critical photoperiod between low- and high-elevation M. laciniatus, an environmental cue that enables populations to initiate flowering at locally appropriate times. To investigate the genetic basis of local adaptation in this key ecological trait, we used a bulk-segregant quantitative trait locus (QTL) analysis approach. We crossed low- and high-elevation populations of M. laciniatus that differ in critical photoperiod to generate an F2 mapping population, phenotyping plants in a short-day common garden. Genomic differentiation (FST and G-statistic) between flowering and non-flowering pools identified 46 regions genome-wide associated with short-day flowering, including a strong peak on chromosome 8 overlapping GA2ox3, a candidate gene in the gibberellin pathway. Another gibberellin gene (GA20ox2) has been implicated in photoperiodic flowering in the close relative Mimulus guttatus. We found additional loci on chromosomes 2 and 11 that appear unique to M. laciniatus. Our findings suggest that local adaptation in reproductive timing may arise through a combination of shared genetic mechanisms and novel alleles in closely related Monkeyflowers, and that the genetic architecture underlying within-species adaptive divergence can be more complex than comparisons across species.

genomics↗

Transcriptomic profiles from stereo-EEGs reveal the local cell microenvironment in human epilepsy

Objectives: Our understanding of the pathomechanisms of epilepsy has improved through techniques that access the living human brain. We recently reported that explanted stereo-electroencephalography (SEEG) electrodes from patients with epilepsy carry residual biomolecules and cells which may be utilised for transcriptome and DNA methylation profiling. Methods: Here, we applied bioinformatic and other analyses to explore the transcriptomes (RNA sequencing-based) of those SEEG cases to better understand the types of recovered transcripts in terms of representation of genes expressed by different cell types, brain structures, and the extent to which the signal may reflect local epileptiform activity. Results: Electrodes from all clinical cases retained protein-coding transcripts which reflected the local molecular microenvironment as well as epileptiform activity. Expression of genes involved in housekeeping functions as well as markers of neuronal activity were consistent between patients and between the electrode locations within the brain. We detected transcripts representing various cell types and subtypes including excitatory and inhibitory neurons, all major classes of glia, and endothelial cells, as well as transcripts enriched in specific brain regions. Several genes showed a gradient of expression depending on the electrode position within the brain. We found examples of gene expression that correlated with epileptiform activity as recorded by SEEG. Interpretation: These findings extend the evidence that SEEG electrodes reflect the molecular microenvironments of brain activity in patients with epilepsy, both at sites of seizure onset and within the wider seizure network. The approach has potential applications in intraoperative surgical decision-making as well as to identify molecular biomarkers or therapeutic targets for the drug-resistant epilepsies.

neuroscience↗