期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/ijms22052346
关键词
reproductive potential; animal model of human disease; domestication; in vivo verification; RNA-seq; differentially expressed gene
资金
- Russian government project [0259-2021-0009]
- Ministry of Science and Higher Education of the Russian Federation [28.12487.2018/12.1]
- Russian Federal Science & Technology Program for the Development of Genetic Technologies
- Russian Science Foundation [19-15-00075]
- Russian Science Foundation [19-15-00075] Funding Source: Russian Science Foundation
The researchers found a reliable association between changes in gene expression in domestic and wild animals with human reproductive potential and their orthologous genes, while gene expression in wild animals better aligns with the normal state of human reproductive potential.
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 chi(2) 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).
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