Behavioral idiosyncrasy reveals genetic control of phenotypic variability

Abstract

Quantitative genetics has primarily focused on describing genetic effects on trait means and largely ignored the effect of alternative alleles on trait variability, potentially missing an important axis of genetic variation contributing to phenotypic differences among individuals. To study the genetic effects on individual-to-individual phenotypic variability (or intragenotypic variability), we used Drosophila inbred lines and measured the spontaneous locomotor behavior of flies walking individually in Y-shaped mazes, focusing on variability in locomotor handedness, an assay optimized to measure variability. We discovered that some lines had consistently high levels of intragenotypic variability among individuals, whereas lines with low variability behaved as although they tossed a coin at each left/right turn decision. We demonstrate that the degree of variability is itself heritable. Using a genome-wide association study (GWAS) for the degree of intragenotypic variability as the phenotype across lines, we identified several genes expressed in the brain that affect variability in handedness without affecting the mean. One of these genes, Ten-a, implicates a neuropil in the central complex of the fly brain as influencing the magnitude of behavioral variability, a brain region involved in sensory integration and locomotor coordination. We validated these results using genetic deficiencies, null alleles, and inducible RNAi transgenes. Our study reveals the constellation of phenotypes that can arise from a single genotype and shows that different genetic backgrounds differ dramatically in their propensity for phenotypic variabililty. Because traditional mean-focused GWASs ignore the contribution of variability to overall phenotypic variation, current methods may miss important links between genotype and phenotype.variability | variance QTL | DGRP | ten-a | personality

Neuromodulatory Regulation of Behavioral Individuality in Zebrafish

“…Behavioral variability in individuals is due to genetic, developmental, pharmacological, environmental and social processes (Kappeler and Anthes, 2010; Laskowski and Bell, 2014). Inter-individual behavioral variation is widely observed across animal phyla and might be under selective pressure during animal evolution (Ayroles et al, 2015; Laurila et al, 2008). However, variation among individuals is often ignored when behavior is quantified as averages with associated dispersions (Geiler-Samerotte et al, 2013).…”

Within-strain variation in behavior differs consistently between common inbred strains of mice

“…A study on variation in gene expression has shown that segregating mouse lines are instrumental to identify loci underlying within-strain variability (Fraser and Schadt 2010). In fact, a recent study using different Drosophila inbred lines confirmed the idea that different genotypes vary dramatically in their propensity for variability, and that loci affecting variability could be mapped (Ayroles et al 2015). We anticipate that systematic automated behavioral analysis panels of inbred or mutant mice in the home-cage could provide the throughput, multidimensionality and sensitivity for genetic dissection of phenotypic robustness in mice as well.…”

Modelling the co-evolution of indirect genetic effects and inherited variability

“…Recently, methods have been developed to detect QTLs that control variability, so-called vQTLs (Rönnegård and Valdar 2011; Rönnegård and Valdar 2012), and these have been found in studies of litter size in pigs (Sell-Kubiak et al 2015), several morphological traits and days to flowering in maize (Ordas et al 2008), and locomotor behavior in fruit flies (Ayroles et al 2015). Furthermore, several mechanisms, resulting in vQTL effects have been proposed (Rönnegård and Valdar 2011; Rönnegård and Valdar 2012), including: epistatic gene interaction, gene-by-environmental interaction, multi-allelic additive effects underlying a QTL and scale of measurement for the observed phenotype.…”