Research Article: A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

Date Published: September 27, 2012

Publisher: Public Library of Science

Author(s): Frank W. Albert, Mehmet Somel, Miguel Carneiro, Ayinuer Aximu-Petri, Michel Halbwax, Olaf Thalmann, Jose A. Blanco-Aguiar, Irina Z. Plyusnina, Lyudmila Trut, Rafael Villafuerte, Nuno Ferrand, Sylvia Kaiser, Per Jensen, Svante Pääbo, Joshua M. Akey

Abstract: Domestication has led to similar changes in morphology and behavior in several animal species, raising the question whether similarities between different domestication events also exist at the molecular level. We used mRNA sequencing to analyze genome-wide gene expression patterns in brain frontal cortex in three pairs of domesticated and wild species (dogs and wolves, pigs and wild boars, and domesticated and wild rabbits). We compared the expression differences with those between domesticated guinea pigs and a distant wild relative (Cavia aperea) as well as between two lines of rats selected for tameness or aggression towards humans. There were few gene expression differences between domesticated and wild dogs, pigs, and rabbits (30–75 genes (less than 1%) of expressed genes were differentially expressed), while guinea pigs and C. aperea differed more strongly. Almost no overlap was found between the genes with differential expression in the different domestication events. In addition, joint analyses of all domesticated and wild samples provided only suggestive evidence for the existence of a small group of genes that changed their expression in a similar fashion in different domesticated species. The most extreme of these shared expression changes include up-regulation in domesticates of SOX6 and PROM1, two modulators of brain development. There was almost no overlap between gene expression in domesticated animals and the tame and aggressive rats. However, two of the genes with the strongest expression differences between the rats (DLL3 and DHDH) were located in a genomic region associated with tameness and aggression, suggesting a role in influencing tameness. In summary, the majority of brain gene expression changes in domesticated animals are specific to the given domestication event, suggesting that the causative variants of behavioral domestication traits may likewise be different.

Partial Text: Domesticated animals differ from their wild relatives in a number of traits, several of which are shared among different domesticated species [1]. Shared traits include conspicuous coat color variation (Figure 1), reduced cranial volume and skeletal gracilization [2] as well as behavioral traits such as reduced fear, higher levels of adult play, and less aggressive behavior [2], [3]. The genetic basis for most domestication traits is unknown [4], [5], with the exception of genetic variants causing between-breed differences in coat color [6]–[8] and some other breed-specific morphological and physiological traits [9], [10]. In addition, a recent genome-wide survey for positive selection in chicken identified genes that may be involved in domestication-related traits [11]. No genetic variants are known to cause domestication-specific behaviors.

We compared gene expression levels in the brains of three pairs of domesticated species and their wild ancestor species. Gene expression differences between domesticated animals and their close wild ancestors were overall small in magnitude, and only a few dozen genes were differentially expressed. We aimed to put these expression differences in context by comparing them to those between domesticated guinea pigs and a more distantly related wild species of cavy and to two lines of rats that were selected for tame and aggressive behavior towards humans as a model for animal domestication [25]. The dog, pig and rabbit comparisons fell in between these two extremes, as expected given most gene expression change accumulates over evolutionary time in parallel with sequence divergence [51]–[52]. The most parsimonious explanation for this correlation is that most observed gene expression differences between species are selectively neutral or nearly neutral [53] or constrained by negative selection [54]. Most of the gene expression changes between domesticated and wild animals are therefore unlikely to have been individually positively selected. In line with this view, expression changes in dogs, pigs and rabbits did not significantly overlap with regions under positive selection associated with domestication, suggesting that the expression changes were not individually driven by positive selection at cis-regulatory sites. The expression changes may be caused by genetic differences in trans, neutral differences in cis, and/or physiological correlates of domestication. We suggest that at present, the differentially expressed genes are best described as domestication phenotypes, i.e. consequences rather than cause of other domestication traits.