Haplotype structure, adaptive history and associations with exploratory behaviour of theDRD4gene region in four great tit (Parus major) populations

Abstract

The assessment of genetic architecture and selection history in genes for behavioural traits is fundamental to our understanding of how these traits evolve. The dopamine receptor D4 (DRD4) gene is a prime candidate for explaining genetic variation in novelty seeking behaviour, a commonly assayed personality trait in animals. Previously, we showed that a single nucleotide polymorphism in exon 3 of this gene is associated with exploratory behaviour in at least one of four Western European great tit (Parus major) populations. These heterogeneous association results were explained by potential variable linkage disequilibrium (LD) patterns between this marker and the causal variant or by other genetic or environmental differences among the populations. Different adaptive histories are further hypothesized to have contributed to these population differences. Here, we genotyped 98 polymorphisms of the complete DRD4 gene including the flanking regions for 595 individuals of the four populations. We show that the LD structure, specifically around the original exon 3 SNP is conserved across the four populations and does not explain the heterogeneous association results. Study-wide significant associations with exploratory behaviour were detected in more than one haplotype block around exon 2, 3 and 4 in two of the four tested populations with different allele effect models. This indicates genetic heterogeneity in the association between multiple DRD4 polymorphisms and exploratory behaviour across populations. The association signals were in or close to regions with signatures of positive selection. We therefore hypothesize that variation in exploratory and other dopamine-related behaviour evolves locally by occasional adaptive shifts in the frequency of underlying genetic variants.

Combined epigenetic and intraspecific variation of theDRD4andSERTgenes influence novelty seeking behavior in great titParus major

“…Subsequent sequencing of the PCR products revealed 9 SNPs, 7 located in the promoter region (detailed in Table 1). 11,12 the In/del ID15 was not observed in our populations. Two SNPs were observed in exon 1 of the DRD4 gene.…”

“…However, although earlier works found an association between DRD4 SNP830 polymorphism and novelty seeking in great tits, 10 this association was only found in one population. 11,12,43 More recently, the SERT gene has been suggested as one of the candidate genes for local adaptation to novel conditions and urbanization. 13 Since we found that one of the main differences between urban and forest great tits probably relied on personality, 27,44 we thought that it could be valuable to look for a direct relationship between SERT polymorphisms, in addition to DRD4, and personality.…”

“…10 However, the relationship between genes and behavior appears far more complex than previously described, as the relationship holds in some populations but not in others. 11 This made Mueller et al 12 suggest that the link between DRD4 gene and personality is context-dependent, probably mediated by certain characteristics of habitat at a local scale. In a recent study, we found that urban and forest great tits differed greatly in novelty seeking behavior, but we were unable to link this variation in behavior to DRD4 SNP830 (Riyahi & Senar personal observation).…”

Evidence from pyrosequencing indicates that natural variation in animal personality is associated with DRD4 DNA methylation

“…association study to detect a significant association with personality traits for several great tit populations (Mueller et al 2013). Although the link between DNA methylation and gene expression is not always straightforward (Jones 2012), we hypothesize that differential methylation at the DRD4 gene affects gene activity and ultimately personality variation.…”

“…In great tits (Parus major), allelic variants in exon 3 of the DRD4 gene are statistically associated with exploratory behaviour in experimental populations that were selected for divergent levels of exploratory behaviour and in hand-reared wild birds (Fidler et al 2007) and also in some (but not all) natural populations (Korsten et al 2010;Mueller et al 2013). However, the observed association could not be linked to any functional (nonsynonymous) single nucleotide polymorphism (SNP) or deletion site within the DRD4 gene or its flanking regions, although there were signs of selection for this polymorphism (Korsten et al 2010;Mueller et al 2013). Thus, DRD4 seems to play a role in heritable variation in great tit exploratory behaviour, but the underlying molecular mechanism remains to be demonstrated.…”