A Bioinformatics Model of Human Diseases on the Basis of Differentially Expressed Genes (of Domestic Versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes.

Gennady Vasiliev,Ekaterina Sharypova,Petr Ponomarenko,Ludmila Savinkova,Dmitry Rasskazov,Anton Bogomolov,Dmitry Oshchepkov,Irina Chadaeva,Alexander Osadchuk,Irina Drachkova,Ludmila Osadchuk,Mikhail Ponomarenko,Nikolay Kolchanov

doi:10.3390/ijms22052346

Abstract

Earlier, after our bioinformatic analysis of single-nucleotide polymorphisms of TATA-binding protein-binding sites within gene promoters on the human Y chromosome, we suggested that human reproductive potential diminishes during self-domestication. Here, we implemented bioinformatics models of human diseases using animal in vivo genome-wide RNA-Seq data to compare the effect of co-directed changes in the expression of orthologous genes on human reproductive potential and during the divergence of domestic and wild animals from their nearest common ancestor (NCA). For example, serotonin receptor 3A (HTR3A) deficiency contributes to sudden death in pregnancy, consistently with Htr3a underexpression in guinea pigs (Cavia porcellus) during their divergence from their NCA with cavy (C. aperea). Overall, 25 and three differentially expressed genes (hereinafter, DEGs) in domestic animals versus 11 and 17 DEGs in wild animals show the direction consistent with human orthologous gene-markers of reduced and increased reproductive potential. This indicates a reliable association between DEGs in domestic animals and human orthologous genes reducing reproductive potential (Pearson’s χ2 test p < 0.001, Fisher’s exact test p < 0.05, binomial distribution p < 0.0001), whereas DEGs in wild animals uniformly match human orthologous genes decreasing and increasing human reproductive potential (p > 0.1; binomial distribution), thus enforcing the norm (wild type).

Highlights

As Theodore Dobzhansky noted, “man is genetically specialized to be unspecialized” [1]
We verified our whole-genome sequence-based a priori hypothesis that human reproductive potential can diminish during self-domestication [42], as
NCA, nearest common ancestor; PADJ, significance (Fisher’s Z-test with those corrections on multiple comparisons, which are available within the RNA-Seq data, as published by their authors [26,28,29])

Summary

Introduction

As Theodore Dobzhansky noted, “man is genetically specialized to be unspecialized” [1]. In all landscapes and all climates of all continents [2,3]. To this end, humans did not adapt anthropometrically to the natural environment like animals do but rather adapted it (as an artificial anthropogenic environment) to their own lives, including the domestication of other organisms to satisfy their own needs and even whims [4,5]. Many behavioral and anatomical differences between domestic and wild animals can correspond to human disease symptoms. Bioinformatics models of human diseases on the basis of differentially expressed genes (DEGs) of domestic versus wild animals (from animal genome-wide transcriptomes determined in vivo) are relevant and useful in the post-genomic era of life sciences

Methods

Results

Conclusion