A bioinformatic search for correspondence between differentially expressed genes of domestic versus wild animals and orthologous human genes altering reproductive potential

Abstract

One of the greatest achievements of genetics in the 20th century is D.K. Belyaev's discovery of destabilizing selection during the domestication of animals and that this selection affects only gene expression regulation (not gene structure) and inf luences systems of neuroendocrine control of ontogenesis in a stressful environment. Among the experimental data generalized by Belyaev's discovery, there are also f indings about accelerated extinc tion of testes' hormonal function and disrupted seasonality of reproduction of domesticated foxes in comparison with their wild congeners. To date, Belyaev's discovery has already been repeatedly conf irmed, for example, by independent observations during deer domestication, during the use of rats as laboratory animals, after the reintroduction of endangered species such as Przewalski's horse, and during the creation of a Siberian reserve population of the Siberian grouse when it had reached an endangered status in natural habitats. A genome-wide comparison among humans, several domestic animals, and some of their wild congeners has given rise to the concept of self-domestication syndrome, which includes autism spectrum disorders. In our previous study, we created a bioinformatic model of human self-domestication syndrome using differentially expressed genes (DEGs; of domestic animals versus their wild congeners) orthologous to the human genes (mainly, nervous-system genes) whose changes in expression affect reproductive potential, i. e., growth of the number of humans in the absence of restrictions caused by limiting factors. Here, we applied this model to 68 human genes whose changes in expression alter the reproductive health of women and men and to 3080 DEGs of domestic versus wild animals. As a result, in domestic animals, we identif ied 16 and 4 DEGs, the expression changes of which are codirected with changes in the expression of the human orthologous genes decreasing and increasing human reproductive potential, respectively. The wild animals had 9 and 11 such DEGs, respectively. This difference between domestic and wild animals was signif icant according to Pearson's χ2 test (p < 0.05) and Fisher's exact test (p < 0.05). We discuss the results from the standpoint of restoration of endangered animal species whose natural habitats are subject to an anthropogenic impact.

Keywords: RNA-Seq; animal model of human disease; domestication; human; most recent common ancestor; reproductive potential.

Table 1.. Examples of the 68 studied human genes for which a signif icant effect of an SNP(s) in the binding site for TATA-binding protein (TBP) on the aff inity of TBP for the promoter of these genes has been previously documented, as have the effects on the levels of their expression and corresponding changes in the reproductive system of women (Chadaeva et al., 2018) and men (Ponomarenko et al., 2020). The complete list is provided in Supplemental Material

Notе. No. is the ID number of a gene in the full list, sorted alphabetically in Supplementary Material. NSNP is the number of candidate SNP markers that signif icantly reduce or increase the aff inity of TBP for a promoter of a gene (Chadaeva et al., 2018; Ponomarenko et al., 2020), thus decreasing (–) or increasing (+) its expression (Mogno et al., 2010; Ponomarenko et al., 2010); impact on reproductive system and health: deterioration (↓) or improvement (↑). Genes: ACKR1 – atypical chemokine receptor 1; DNMT1 – DNA methyltransferase 1; PLCXD1 – phosphatidylinositol-specif ic phospholipase CX domain – containing 1; ZFY – Y- linked zinc f inger protein.

Table 2.. The analyzed RNA-Seq data on DEGs of domestic vs wild animals available in the PubMed database (Lu, 2011)

Table 3.. Examples of the studied DEGs of domestic vs wild animals. These DEGs are collectively characterized in Table 2

Notе. log2 – expression in domesticated relative to wild animals (in log2 units); p – statistical signif icance as determined by the authors cited in column ix. Genes: Ckbl – creatine kinase B-like protein; Adm – adrenomedullin; Hpd – 4-hydroxyphenylpyruvate dioxygenase; Mdk – midkine; C7 – component 7 of the complement system of innate immunity; Ano3 – anoctamin 3; Agt – angiotensinogen; Gp2 – glycoprotein 2; ApoD – apolipoprotein D; Pgk1 – phosphoglycerate kinase 1; Aqp1 – aquaporin 1; Irf6 – interferon regulatory factor 6; Alb – albumin; Fst – follistatin.

Table 4.. A comparison between the effects of expression changes of human orthologous genes on reproductive potential and expression changes during the divergence of domestic and wild animals from their most recent common ancestor

Table 4end.. Table 4 (end)

Notе. See the footnote of Table 3. Genes: Apoa1 – apolipoprotein A1; Cetp – cholesteryl ester transfer protein; Cyp17a1 – steroid 17α-monooxygenase; Gcg – glucagon; Il1b – interleukin 1β; Nr5a1 – steroidogenic factor 1; F3, F7, and Proc – blood coagulation factors III, VII, and XIV, respectively; Gh1 – growth hormone; HBD, Hba1, Hbad, Hbbl, Hbm, and Hbz1 are hemoglobin subunits δ, α1, αD, β-like, μ, and ζ1, respectively; Esr2 – estrogen receptor 2; Il9r – interleukin 9 receptor; Pgr – progesterone receptor; Slc25a6 – mitochondrial solute transporter.