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Rand, D. M.

Publications and source records attributed to Rand, D. M..

4 recordsLinked to original sources

The Genetic Architecture of Robustness for Flight Performance in Drosophila

A central challenge of quantitative genetics is partitioning phenotypic variation into genetic and non-genetic components. These non-genetic components are usually interpreted as environmental effects; however, variation between genetically identical individuals in a common environment can still exhibit phenotypic variation. A traits resistance to variation is called robustness, though the genetics underlying it are poorly understood. Accordingly, we performed an association study on a previously studied, whole organism trait: flight performance. Using 197 of the Drosophila Genetic Reference Panel (DGRP) lines, we surveyed variation at the level of single nucleotide polymorphisms and whole genes using additive, marginal, and epistatic analyses that associated with robustness for flight performance. Many genes had developmental and neurodevelopmental annotations, and many more were identified from associations that differed between sexes. Additionally, many genes were pleiotropic, with several annotated for fitness-associated traits (e.g. gametogenesis and courtship). Our results corroborate a previous study for genetic modifiers of micro-environmental variation, and have sizable overlap with studies for modifiers of wing morphology and courtship behavior. These results point to an important and shared role for genetic modifiers of robustness of flight performance affecting development, neurodevelopment, and behavior.

genetics

Ecological load and balancing selection in circumboreal barnacles

Acorn barnacle adults experience environmental heterogeneity at various spatial scales of their circumboreal habitat, raising the question of how adaptation to high environmental variability is maintained in the face of strong juvenile dispersal and mortality. Here we show that 4% of genes in the barnacle genome experience balancing selection across the entire range of the species. Many of these genes harbor mutations maintained across 2 million years of evolution between the Pacific and Atlantic oceans. These genes are involved in ion regulation, pain reception, and heat tolerance, functions which are essential in highly variable ecosystems. The data also reveal complex population structure within and between basins, driven by the trans-Arctic interchange and the last glaciation. Divergence between Atlantic and Pacific populations is high, foreshadowing the onset of allopatric speciation, and suggesting that balancing selection is strong enough to maintain functional variation for millions of years in the face of complex demography.

evolutionary biology

FreeClimber: Automated quantification of climbing performance in Drosophila, with examples from mitonuclear genotypes

Negative geotaxis (climbing) performance is a useful metric for quantifying Drosophila health and vigor. Manual methods to quantify climbing performance are slow, tedious, and may be systematically biased, while available computational methods have inflexible hardware or software requirements. We present an alternative: FreeClimber. This open source, Python-based pipeline subtracts a video’s static background to improve spot detection for moving flies in heterogeneous backgrounds. FreeClimber calculates a cohort’s velocity as the slope of the most linear portion of a mean-vertical position vs. time plot. It can run from a graphical user interface for parameter optimization or a command line interface for high-throughput and automated batch processing. It outputs calculated slopes, spot locations for follow up analyses such as tracking, and several visualizations and diagnostic plots. We demonstrate FreeClimber’s utility in a longitudinal study for endurance exercise performance in Drosophila using six distinct mitochondrial haplotypes paired with a common w1118 nuclear background.Summary statement FreeClimber quantifies the climbing velocity for a group of flies, eliminating systematic biases associated with traditional manual methods in a high throughput and automated (graphical and/or command line-based) platform.List of Symbols and AbbreviationsecceccentricityGUIGraphical User Interfacemito-nuclearMitochondrial-nuclearmitotypesMitochondrial haplotypeOreROregon RROIRegion of InterestyakyakubaZimZimbabwe53View Full Text

bioinformatics

Natural variation in the regulation of neurodevelopmental genes modifies flight performance in Drosophila

The winged insects of the order Diptera are colloquially named for their most recognizable phenotype: flight. These insects rely on flight for a number of important life history traits, like dispersal, foraging, and courtship. Despite the importance of flight, relatively little is known about the genetic architecture of variation for flight performance. Accordingly, we sought to uncover the genetic modifiers of flight using a measure of flies reaction and response to an abrupt drop in a vertical flight column. We conducted an association study using 197 of the Drosophila Genetic Reference Panel (DGRP) lines, and identified a combination of additive and marginal variants, epistatic interactions, whole genes, and enrichment across interaction networks. We functionally validated 13 of these candidate genes (Adgf-A/Adgf-A2/CG32181, bru1, CadN, CG11073, CG15236, CG9766, CREG, Dscam4, form3, fry, Lasp/CG9692, Pde6, Snoo) contribution to flight, two of which (fry and Snoo) also validate a whole gene analysis we introduce for the DGRP: PEGASUS_flies. Overall, our results suggest modifiers of muscle and wing morphology, and peripheral and central nervous system assembly and function are all important for flight performance. Additionally, we identified ppk23, an Acid Sensing Ion Channel (ASIC) homolog, as an important hub for epistatic interactions. These results represent a snapshot of the genetic modifiers affecting drop-response flight performance in Drosophila, with implications for other insects. It also draws connections between genetic modifiers of performance and BMP signaling and ASICs as targets for treating neurodegeneration and neurodysfunction. Author summaryInsect flight is a widely recognizable phenotype of winged insects, hence the name: flies. While fruit flies, or Drosophila melanogaster, are a genetically tractable model, flight performance is a highly integrative phenotype, making it challenging to comprehensively identify the genetic modifiers that contribute to its genetic architecture. Accordingly, we screened 197 Drosophila Genetic Reference Panel lines for their ability to react and respond to an abrupt drop. Using several computational tools, we successfully identified several additive, marginal, and epistatic variants, as well as whole genes and altered sub-networks of gene-gene and protein-protein interaction networks, demonstrating the benefits of using multiple methodologies to elucidate the genetic architecture of complex traits more generally. Many of these significant genes and variants mapped to regions of the genome that affect development of sensory and motor neurons, wing and muscle development, and regulation of transcription factors. We also introduce PEGASUS_flies, a Drosophila-adapted version of the PEGASUS platform first used in human studies, to infer gene-level significance of association based on the distribution of individual variant P-values. Our results contribute to the debate over the relative importance of individual, additive factors and epistatic, or higher order, interactions, in the mapping of genotype to phenotype.

genetics