Domestication Explains Two-Thirds of Differential-Gene-Expression Variance between Domestic and Wild Animals; The Remaining One-Third Reflects Intraspecific and Interspecific Variation

SIMPLE SUMMARY: Before genomes were sequenced, zoologists had discovered destabilizing selection as a general pattern of animal domestication that in foxes and minks had yielded fur colors never seen in the wild. Today, known genomes of humans and domestic and wild animals arouse interest in a common whole-genome pattern of animal domestication that may at least explain differences between the effects of natural and artificial environments on organisms. Accordingly, here we identified genes differing in expression between tame and aggressive rats (a laboratory domestication model) to compare them with all such known changes of genes’ activity (available in databases) in other domestic versus wild animals (e.g., dogs versus wolves). The results show that the majority of these genes changed their expression similarly among all the domestic versus wild animals studied, i.e., explained two-thirds of the variance, while the remaining one-third reflected animal intraspecific and interspecific variation, just as the gold standard of variation in nature. Accordingly, here we found that the artificial environment of domestic animals alters activities of genes in the same direction as that seen in corresponding human genes during human diseases, whereas the natural environment maintains a normal gene expression pattern in wild animals (matching human health). ABSTRACT: Belyaev’s concept of destabilizing selection during domestication was a major achievement in the XX century. Its practical value has been realized in commercial colors of the domesticated fox that never occur in the wild and has been confirmed in a wide variety of pet breeds. Many human disease models involving animals allow to test drugs before human testing. Perhaps this is why investigators doing transcriptomic profiling of domestic versus wild animals have searched for breed-specific patterns. Here we sequenced hypothalamic transcriptomes of tame and aggressive rats, identified their differentially expressed genes (DEGs), and, for the first time, applied principal component analysis to compare them with all the known DEGs of domestic versus wild animals that we could find. Two principal components, PC1 and PC2, respectively explained 67% and 33% of differential-gene-expression variance (hereinafter: log(2) value) between domestic and wild animals. PC1 corresponded to multiple orthologous DEGs supported by homologs; these DEGs kept the log(2) value sign from species to species and from tissue to tissue (i.e., a common domestication pattern). PC2 represented stand-alone homologous DEG pairs reversing the log(2) value sign from one species to another and from tissue to tissue (i.e., representing intraspecific and interspecific variation).