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Comparative Study
. 2020 Oct 1;12(10):1918-1928.
doi: 10.1093/gbe/evaa158.

Brain Transcriptomics of Wild and Domestic Rabbits Suggests That Changes in Dopamine Signaling and Ciliary Function Contributed to Evolution of Tameness

Daiki X Sato  1   2 , Nima Rafati  2   3 , Henrik Ring  4 , Shady Younis  2 , Chungang Feng  2 , José A Blanco-Aguiar  5   6 , Carl-Johan Rubin  2 , Rafael Villafuerte  7 , Finn Hallböök  4 , Miguel Carneiro  5   8 , Leif Andersson  2   9   10
Affiliations
Comparative Study

Brain Transcriptomics of Wild and Domestic Rabbits Suggests That Changes in Dopamine Signaling and Ciliary Function Contributed to Evolution of Tameness

Daiki X Sato et al. Genome Biol Evol. .

Abstract

Domestication has resulted in immense phenotypic changes in animals despite their relatively short evolutionary history. The European rabbit is one of the most recently domesticated animals, but exhibits distinct morphological, physiological, and behavioral differences from their wild conspecifics. A previous study revealed that sequence variants with striking allele frequency differences between wild and domestic rabbits were enriched in conserved noncoding regions, in the vicinity of genes involved in nervous system development. This suggests that a large proportion of the genetic changes targeted by selection during domestication might affect gene regulation. Here, we generated RNA-sequencing data for four brain regions (amygdala, hypothalamus, hippocampus, and parietal/temporal cortex) sampled at birth and revealed hundreds of differentially expressed genes (DEGs) between wild and domestic rabbits. DEGs in amygdala were significantly enriched for genes associated with dopaminergic function and all 12 DEGs in this category showed higher expression in domestic rabbits. DEGs in hippocampus were enriched for genes associated with ciliary function, all 21 genes in this category showed lower expression in domestic rabbits. These results indicate an important role of dopamine signaling and ciliary function in the evolution of tameness during rabbit domestication. Our study shows that gene expression in specific pathways has been profoundly altered during domestication, but that the majority of genes showing differential expression in this study have not been the direct targets of selection.

Keywords: amygdala; domestication; dopamine; evolution of tameness; the European rabbit; transcriptome.

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Figures

<sc>Fig</sc>. 1.
Fig. 1.
(A) Overlap among genes showing differential expression between wild versus domestic rabbits in four brain regions. (B) Twenty-seven differentially expressed genes were found to be shared among all brain regions. Genes with selection signal between domestic and wild rabbits are highlighted in red. Purple and green represent higher expression in wild and domestic rabbits, respectively. Genes with an asterisk denote manually curated genes with insufficient annotation of their names.
<sc>Fig</sc>. 2.
Fig. 2.
Protein–protein interaction networks among differentially expressed genes detected in (A) amygdala and (B) hippocampus. Only genes connected in networks are shown, and ones belonging to clustered subnetworks estimated by Cytoscape are highlighted in different colors. Black represents ribosomal gene clusters in both figures. Clusters corresponding to the genes involved in dopaminergic neurotransmission in amygdala and dynein complex and cilium axoneme in hippocampus are highlighted in green and purple, respectively. Defined dopaminergic or ciliary genes based on the clustering and enrichment analysis (DAVID and GREAT) are shown with large symbols. Genes associated with signals of selection are highlighted in red. The thickness of the line indicates the strength of data support analyzed by STRING. Some of the genes without annotation by STRING are shown with the name of orthologs in parentheses (an asterisk denotes manual curation). (C) Changes in expression levels of all the dopaminergic genes showing differential expression in amygdala and all the ciliary genes showing differential expression in hippocampus. Positive values on the y-axis represent higher expression in wild rabbits, and high expression in domestic and wild rabbits are shown in green and purple, respectively.
<sc>Fig</sc>. 3.
Fig. 3.
Signatures of selection for genomic regions harboring (A) TCEAL2, (B) NTRK1, (C) DNAH11, and (D) RPL21. Black lines and points represent window-based (±5 kb) and per-site dAF values, respectively. Red dashed lines indicate top 1% of dAF calculated from its distribution across the genome. A red bold line in (C) represents a selective sweep reported in Carneiro et al. (2014). Both genes denoted with asterisk in (A) seem to be orthologs of human NXF2.
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