Cargando…

A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans

Aggressiveness is a hereditary behavioral pattern that forms a social hierarchy and affects the individual social rank and accordingly quality and duration of life. Thus, genome-wide studies of human aggressiveness are important. Nonetheless, the aggressiveness-related genome-wide studies have been...

Descripción completa

Detalles Bibliográficos
Autores principales: Oshchepkov, Dmitry, Ponomarenko, Mikhail, Klimova, Natalya, Chadaeva, Irina, Bragin, Anatoly, Sharypova, Ekaterina, Shikhevich, Svetlana, Kozhemyakina, Rimma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923764/
https://www.ncbi.nlm.nih.gov/pubmed/31921305
http://dx.doi.org/10.3389/fgene.2019.01267
_version_ 1783481589042249728
author Oshchepkov, Dmitry
Ponomarenko, Mikhail
Klimova, Natalya
Chadaeva, Irina
Bragin, Anatoly
Sharypova, Ekaterina
Shikhevich, Svetlana
Kozhemyakina, Rimma
author_facet Oshchepkov, Dmitry
Ponomarenko, Mikhail
Klimova, Natalya
Chadaeva, Irina
Bragin, Anatoly
Sharypova, Ekaterina
Shikhevich, Svetlana
Kozhemyakina, Rimma
author_sort Oshchepkov, Dmitry
collection PubMed
description Aggressiveness is a hereditary behavioral pattern that forms a social hierarchy and affects the individual social rank and accordingly quality and duration of life. Thus, genome-wide studies of human aggressiveness are important. Nonetheless, the aggressiveness-related genome-wide studies have been conducted on animals rather than humans. Recently, in our genome-wide study, we uncovered natural selection against underexpression of human aggressiveness-related genes and proved it using F1 hybrid mice. Simultaneously, this natural selection equally supports two opposing traits in humans (dominance and subordination) as if self-domestication could have happened with its disruptive natural selection. Because there is still not enough scientific evidence that this could happen, here, we verified this natural selection pattern using quantitative PCR and two outbred rat lines (70 generations of artificial selection for aggressiveness or tameness, hereinafter: domestication). We chose seven genes—Cacna2d3, Gad2, Gria2, Mapk1, Nos1, Pomc, and Syn1—over- or underexpression of which corresponds to aggressive or domesticated behavior (in humans or mice) that has the same direction as natural selection. Comparing aggressive male rats with domesticated ones, we found that these genes are overexpressed statistically significantly in the hypothalamus (as a universal behavior regulator), not in the periaqueductal gray, where there was no aggressiveness-related expression of the genes in males. Database STRING showed statistically significant associations of the human genes homologous to these rat genes with long-term depression, circadian entrainment, Alzheimer’s disease, and the central nervous system disorders during chronic IL-6 overexpression. This finding more likely supports positive perspectives of further studies on self-domestication syndromes.
format Online
Article
Text
id pubmed-6923764
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-69237642020-01-09 A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans Oshchepkov, Dmitry Ponomarenko, Mikhail Klimova, Natalya Chadaeva, Irina Bragin, Anatoly Sharypova, Ekaterina Shikhevich, Svetlana Kozhemyakina, Rimma Front Genet Genetics Aggressiveness is a hereditary behavioral pattern that forms a social hierarchy and affects the individual social rank and accordingly quality and duration of life. Thus, genome-wide studies of human aggressiveness are important. Nonetheless, the aggressiveness-related genome-wide studies have been conducted on animals rather than humans. Recently, in our genome-wide study, we uncovered natural selection against underexpression of human aggressiveness-related genes and proved it using F1 hybrid mice. Simultaneously, this natural selection equally supports two opposing traits in humans (dominance and subordination) as if self-domestication could have happened with its disruptive natural selection. Because there is still not enough scientific evidence that this could happen, here, we verified this natural selection pattern using quantitative PCR and two outbred rat lines (70 generations of artificial selection for aggressiveness or tameness, hereinafter: domestication). We chose seven genes—Cacna2d3, Gad2, Gria2, Mapk1, Nos1, Pomc, and Syn1—over- or underexpression of which corresponds to aggressive or domesticated behavior (in humans or mice) that has the same direction as natural selection. Comparing aggressive male rats with domesticated ones, we found that these genes are overexpressed statistically significantly in the hypothalamus (as a universal behavior regulator), not in the periaqueductal gray, where there was no aggressiveness-related expression of the genes in males. Database STRING showed statistically significant associations of the human genes homologous to these rat genes with long-term depression, circadian entrainment, Alzheimer’s disease, and the central nervous system disorders during chronic IL-6 overexpression. This finding more likely supports positive perspectives of further studies on self-domestication syndromes. Frontiers Media S.A. 2019-12-13 /pmc/articles/PMC6923764/ /pubmed/31921305 http://dx.doi.org/10.3389/fgene.2019.01267 Text en Copyright © 2019 Oshchepkov, Ponomarenko, Klimova, Chadaeva, Bragin, Sharypova, Shikhevich and Kozhemyakina http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Oshchepkov, Dmitry
Ponomarenko, Mikhail
Klimova, Natalya
Chadaeva, Irina
Bragin, Anatoly
Sharypova, Ekaterina
Shikhevich, Svetlana
Kozhemyakina, Rimma
A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans
title A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans
title_full A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans
title_fullStr A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans
title_full_unstemmed A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans
title_short A Rat Model of Human Behavior Provides Evidence of Natural Selection Against Underexpression of Aggressiveness-Related Genes in Humans
title_sort rat model of human behavior provides evidence of natural selection against underexpression of aggressiveness-related genes in humans
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923764/
https://www.ncbi.nlm.nih.gov/pubmed/31921305
http://dx.doi.org/10.3389/fgene.2019.01267
work_keys_str_mv AT oshchepkovdmitry aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT ponomarenkomikhail aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT klimovanatalya aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT chadaevairina aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT braginanatoly aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT sharypovaekaterina aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT shikhevichsvetlana aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT kozhemyakinarimma aratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT oshchepkovdmitry ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT ponomarenkomikhail ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT klimovanatalya ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT chadaevairina ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT braginanatoly ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT sharypovaekaterina ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT shikhevichsvetlana ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans
AT kozhemyakinarimma ratmodelofhumanbehaviorprovidesevidenceofnaturalselectionagainstunderexpressionofaggressivenessrelatedgenesinhumans