Epigenetic mechanisms modulate differences in Drosophila foraging behavior

Abstract

Little is known about how genetic variation and epigenetic marks interact to shape differences in behavior. The foraging (for) gene regulates behavioral differences between the rover and sitter Drosophila melanogaster strains, but the molecular mechanisms through which it does so have remained elusive. We show that the epigenetic regulator G9a interacts with for to regulate strain-specific adult foraging behavior through allele-specific histone methylation of a for promoter (pr4). Rovers have higher pr4 H3K9me dimethylation, lower pr4 RNA expression, and higher foraging scores than sitters. The rover-sitter differences disappear in the presence of G9a null mutant alleles, showing that G9a is necessary for these differences. Furthermore, rover foraging scores can be phenocopied by transgenically reducing pr4 expression in sitters. This compelling evidence shows that genetic variation can interact with an epigenetic modifier to produce differences in gene expression, establishing a behavioral polymorphism in Drosophila.histone methylation | epigenetics | behavior | foraging | Drosophila melanogaster A lthough it has been shown that variation in human and animal behavior correlates with genetic polymorphisms and epigenetic regulation (1, 2), causal links among genetic variation, epigenetic regulation, and behavior have not been established.The foraging (for) gene in Drosophila melanogaster is a complex gene that encodes several different isoforms of a cGMP-dependent protein kinase (3). for regulates various behavioral and physiological phenotypes in the fly and other organisms, including humans (4-9). Importantly, this gene, with its rover and sitter allelic variants, is known to give rise to naturally occurring behavioral variations in D. melanogaster. Larvae with the rover allele move longer distances while foraging than those with sitter alleles, and the rover allele exhibits genetic dominance over the sitter in this trait (3). for also affects rover-sitter differences in foraging behavior in adult flies (10, 11). These rover-sitter behavioral differences have been shown to arise from genetic variation in the for gene, but until now the molecular mechanisms underlying rover-sitter differences have remained elusive.for has four separate transcription start sites and one transcription termination site encoding at least 21 different transcripts, which cluster into four transcript classes of similar coding sequences according to promoter: pr1, pr2, pr3, and pr4 (4). This complexity could contain the key to understanding the regulation of rover-sitter behavioral differences as well as for's pleiotropic functions. The function of each of for's transcripts and how they are regulated are currently unknown.Epigenetic modifiers play an important role in depositing marks that recruit transcription factors and regulate expression. Drosophila G9a (dG9a, EHMT) is an epigenetic modifier known to methylate the regions of the for promoters (12). G9a is one of three histone methyltransferases that catalyze H3K9me2 in flies. While...

Distinct functions of a cGMP-dependent protein kinase in nerve terminal growth and synaptic vesicle cycling

“…Kinases can phosphorylate multiple targets, be expressed in different cells, have different subcellular expression patterns and be temporally activated at different times, all of which are means of pleiotropy. FOR has been implicated in behavioural pleiotropy (Allen et al, 2017;Anreiter et al, 2017;Allen et al, 2018;Anreiter and Sokolowski, 2018). Here, we show distinct spatial and temporal requirements for FOR at the synapse.…”

Distributed physiology and the molecular basis of social life in eusocial insects

“…It appears that gene regulatory networks evolve through both changes in the regulation of conserved loci and incorporation of new players: novel loci are more likely to be incorporated into distal parts of gene regulatory networks and be expressed in novel or secretory tissues, while conserved loci are more likely to undergo changes to transcriptional regulation in conserved tissues16,95 .The function of conserved members of physiological regulatory processes can be influenced by sequence changes, new regulatory connections, or other contextual changes. For example the cGMP-dependent protein kinase G enzyme (known as foraging in Drosophila ) is famous for being a conserved player in the neurobiology of foraging and metabolic regulation across vertebrate and invertebrate taxa[96][97][98] . While the homology of the PKG locus is indeed deeply conserved, the action of PKG is cell-type specific and also probably depends on the identity of downstream phosphorylation targets.…”

Generating high quality assemblies for genomic analysis of transposable elements

“…To illustrate this, we estimated CUSCO values for several publicly available assemblies of different D. melanogaster strains (supplementary fig. 10; (McCoy et al, 2014;Vicoso and Bachtrog, 2015;Anreiter et al, 2017;Singhal et al, 2017;Chakraborty et al, 2019;Ellison and Cao, 2020)). Assemblies based on ONT and PacBio long reads have a similar quality than our assemblies of Pi2 and Canton-S (supplementary fig.…”