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Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective

Evolutionary changes in brain and craniofacial development have endowed humans with unique cognitive and social skills, but also predisposed us to debilitating disorders in which these traits are disrupted. What are the developmental genetic underpinnings that connect the adaptive evolution of our c...

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Autores principales: Zug, Roman, Uller, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426018/
https://www.ncbi.nlm.nih.gov/pubmed/37588924
http://dx.doi.org/10.1017/ehs.2022.42
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author Zug, Roman
Uller, Tobias
author_facet Zug, Roman
Uller, Tobias
author_sort Zug, Roman
collection PubMed
description Evolutionary changes in brain and craniofacial development have endowed humans with unique cognitive and social skills, but also predisposed us to debilitating disorders in which these traits are disrupted. What are the developmental genetic underpinnings that connect the adaptive evolution of our cognition and sociality with the persistence of mental disorders with severe negative fitness effects? We argue that loss of function of genes involved in transcriptional regulation represents a crucial link between the evolution and dysfunction of human cognitive and social traits. The argument is based on the haploinsufficiency of many transcriptional regulator genes, which makes them particularly sensitive to loss-of-function mutations. We discuss how human brain and craniofacial traits evolved through partial loss of function (i.e. reduced expression) of these genes, a perspective compatible with the idea of human self-domestication. Moreover, we explain why selection against loss-of-function variants supports the view that mutation-selection-drift, rather than balancing selection, underlies the persistence of psychiatric disorders. Finally, we discuss testable predictions.
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spelling pubmed-104260182023-08-16 Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective Zug, Roman Uller, Tobias Evol Hum Sci Perspective Evolutionary changes in brain and craniofacial development have endowed humans with unique cognitive and social skills, but also predisposed us to debilitating disorders in which these traits are disrupted. What are the developmental genetic underpinnings that connect the adaptive evolution of our cognition and sociality with the persistence of mental disorders with severe negative fitness effects? We argue that loss of function of genes involved in transcriptional regulation represents a crucial link between the evolution and dysfunction of human cognitive and social traits. The argument is based on the haploinsufficiency of many transcriptional regulator genes, which makes them particularly sensitive to loss-of-function mutations. We discuss how human brain and craniofacial traits evolved through partial loss of function (i.e. reduced expression) of these genes, a perspective compatible with the idea of human self-domestication. Moreover, we explain why selection against loss-of-function variants supports the view that mutation-selection-drift, rather than balancing selection, underlies the persistence of psychiatric disorders. Finally, we discuss testable predictions. Cambridge University Press 2022-09-26 /pmc/articles/PMC10426018/ /pubmed/37588924 http://dx.doi.org/10.1017/ehs.2022.42 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.
spellingShingle Perspective
Zug, Roman
Uller, Tobias
Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective
title Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective
title_full Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective
title_fullStr Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective
title_full_unstemmed Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective
title_short Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective
title_sort evolution and dysfunction of human cognitive and social traits: a transcriptional regulation perspective
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10426018/
https://www.ncbi.nlm.nih.gov/pubmed/37588924
http://dx.doi.org/10.1017/ehs.2022.42
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