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

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: log2 value) between domestic and wild animals. PC1 corresponded to multiple orthologous DEGs supported by homologs; these DEGs kept the log2 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 log2 value sign from one species to another and from tissue to tissue (i.e., representing intraspecific and interspecific variation).

Stress Reactivity, Susceptibility to Hypertension, and Differential Expression of Genes in Hypertensive Compared to Normotensive Patients

“…For this purpose, using the PubMed database [ 69 ], we collected all the transcriptomes (that we could find) of domestic animals compared with their wild congeners, as shown in Table 8 . The bottom row of this table indicates that we found 2393 DEGs in the tissues of domestic versus wild animals, as cited in the rightmost column of this table [ 72 , 187 , 188 , 189 , 190 , 191 , 192 , 193 ].…”

“…For this purpose, using the PubMed database [69], we collected all the transcriptomes (that we could find) of domestic animals compared with their wild congeners, as shown in Table 8. The bottom row of this table indicates that we found 2393 DEGs in the tissues of domestic versus wild animals, as cited in the rightmost column of this table [72,[187][188][189][190][191][192][193]. Using the 42 DEGs (from the hippocampus of the tame versus aggressive rats) identified here (Table 2), together with these 2393 DEGs of domestic versus wild animals (Table 8), we revealed three β-protocadherin DEGs and seven hemoglobin subunit DEGs, which are compared in Table 9 with the human homologous genes (HBB, HBD, and PCDHB9), annotated with respect to hypertension in Table S3.…”

“…In this work, we analyzed all the publicly available independent experimental RNA-Seq datasets-on transcriptomes from the tissues of hypertensive versus normotensive patients [26][27][28][29][30][31][32][33][34][35][36][37][38][39], hypertensive versus normotensive animals [7,[40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57], and domestic versus wild animals [72,[176][177][178][179][180][181][182][183][184][185][186][187][188][189][190][191][192][193].…”

“…In the present work, we meta-analyzed our eight abovementioned RNA-Seq datasets to ensure out of caution that among them (together with those available in PubMed [ 69 ]), there are still no invariant molecular markers of hypertension. Accordingly, we sequenced the hippocampal transcriptome of tame compared to aggressive rats and identified the stress-reactivity-related rat DEGs and—using our bioinformatics model [ 70 , 71 , 72 ]—compared them by homology with all the available hypertension-related animal DEGs that we could find. The results were verified using the DEGs of hypertensive versus normotensive patients.…”

Editorial: Bioinformatics of Genome Regulation, Volume II

“…They show that the disruptive natural selection of human immunostimulatory and immunosuppressive genes concurrently elevates and reduces the risk of rheumatoid arthritis. The authors hypothesize that rheumatoid arthritis in humans could be a self-domestication syndrome referring to evolution patterns in domestic animals ( Chadaeva et al, 2021 ).…”