Selection on DRD4 haplotypes in a natural great tit population in relation to personality

Abstract: Variations in neurotransmitter-related genes are reported to be associated with personality traits among humans. One of the genes, the dopamine receptor (Drd4) gene showed a relation with novelty-seeking behaviour or curiosity traits. Moreover, in human, the dopamine receptor is the target site for drugs used in treating Parkinson’s disease and schizophrenia. Non human vertebrates and free living species can provide better understanding of the genotype personality relationships as they can be measured under standardized selection experiments. The great tit (Parus major) is one such model species used in these types of studies. Temperamental traits are heritable as well as linked to fitness traits, which makes it important in the study of ecology and evolution. A recent study by Fidler et al (2007) detected 73 polymorphisms (66 SNPs and 7 indels) in the great tit Drd4 orthologue (GenBank: DQ006801.1) The objectives of the current study were i) to amplify and sequence selected regions in dopamine receptor gene in two lines (slow and fast) of great tit, including from the wild and ii) to identify SNPs and haplotypes within this gene. iii) To develop a strategy for typing the different haplotypes within a large population (> 1000 animals). Two different lines of a great tit population, selected for slow and fast Early Exploratory Behaviour (EEB) were considered for the experiment. These birds were reared under captive conditions at Netherlands Institute of Ecology (NIOO). A total of 19 birds from the fast line and 21 birds from the slow line were used in the study. Apart from the captive population of these two lines, a wild population (N=10) representing an out-group was also tested to identify the pattern followed under natural selection. Twelve regions within the dopamine receptor gene (Fig 1) were selected based on either SNP density or their proximity to indels. Six haplotype blocks were identified within the gene. The SNPs constituting these blocks had, on an average, a MAF of 0.2 and were in high LD, which would eventually make it easier to find them and thereby enable to genotype a larger population using these six haplotype blocks. A significant association of SNPs 79 and 81 with the slow phenotype was observed, suggestive of a region which could be in association with this trait. SNP 76, which was reported (Fidler et al, 2007) to be associated with novelty seeking behaviour was found to be not significant. However, these SNPs are in close correlation (r2=0.69) with SNP 76 and hence indicate a region of strong association with the trait. The effect of introns, rather than the coding regions, in gene regulation could be the possible reason for this strong association. Further, a low level of LD within the gene supports the speculation that the causative mutation is within the dopamine receptor gene. The results from the wild out group weren’t significant owing to their small number but a highly similar trend was noticed suggestive of an association with the trait. A more detailed study could explain the trends followed in natural selection and evolution.