Cargando…

Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation

Antagonistic pleiotropy (AP), the ability of a gene to show opposing effects in different phenotypes, has been identified in various life history traits and complex disorders, indicating its fundamental role in balancing fitness over the course of evolution. It is intuitive that natural selection mi...

Descripción completa

Detalles Bibliográficos
Autores principales: Yadav, Anupama, Radhakrishnan, Aparna, Bhanot, Gyan, Sinha, Himanshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426359/
https://www.ncbi.nlm.nih.gov/pubmed/25711830
http://dx.doi.org/10.1534/g3.115.017020
_version_ 1782370582131638272
author Yadav, Anupama
Radhakrishnan, Aparna
Bhanot, Gyan
Sinha, Himanshu
author_facet Yadav, Anupama
Radhakrishnan, Aparna
Bhanot, Gyan
Sinha, Himanshu
author_sort Yadav, Anupama
collection PubMed
description Antagonistic pleiotropy (AP), the ability of a gene to show opposing effects in different phenotypes, has been identified in various life history traits and complex disorders, indicating its fundamental role in balancing fitness over the course of evolution. It is intuitive that natural selection might maintain AP to allow organisms phenotypic flexibility in different environments. However, despite several attempts, little evidence exists for its role in adaptation. We performed a meta-analysis in yeast to identify the genetic basis of AP in bi-parental segregants, natural isolates, and a laboratory strain genome-wide deletion collection, by comparing growth in favorable and stress conditions. We found that whereas AP was abundant in the synthetic populations, it was absent in the natural isolates. This finding indicated resolution of trade-offs, i.e., mitigation of trade-offs over evolutionary history, probably through accumulation of compensatory mutations. In the deletion collection, organizational genes showed AP, suggesting ancient resolutions of trade-offs in the basic cellular pathways. We find abundant AP in the segregants, greater than estimated in the deletion collection or observed in previous studies, with IRA2, a negative regulator of the Ras/PKA signaling pathway, showing trade-offs across diverse environments. Additionally, IRA2 and several other Ras/PKA pathway genes showed balancing selection in isolates of S. cerevisiae and S. paradoxus, indicating that multiple alleles maintain AP in this pathway in natural populations. We propose that during AP resolution, retaining the ability to vary signaling pathways such as Ras/PKA, may provide organisms with phenotypic flexibility. However, with increasing organismal complexity AP resolution may become difficult. A partial resolution of AP could manifest as complex human diseases, and the inability to resolve AP may play a role in speciation. Our findings suggest that testing a universal phenomenon like AP across multiple experimental systems may elucidate mechanisms underlying its regulation and evolution.
format Online
Article
Text
id pubmed-4426359
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Genetics Society of America
record_format MEDLINE/PubMed
spelling pubmed-44263592015-05-13 Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation Yadav, Anupama Radhakrishnan, Aparna Bhanot, Gyan Sinha, Himanshu G3 (Bethesda) Investigations Antagonistic pleiotropy (AP), the ability of a gene to show opposing effects in different phenotypes, has been identified in various life history traits and complex disorders, indicating its fundamental role in balancing fitness over the course of evolution. It is intuitive that natural selection might maintain AP to allow organisms phenotypic flexibility in different environments. However, despite several attempts, little evidence exists for its role in adaptation. We performed a meta-analysis in yeast to identify the genetic basis of AP in bi-parental segregants, natural isolates, and a laboratory strain genome-wide deletion collection, by comparing growth in favorable and stress conditions. We found that whereas AP was abundant in the synthetic populations, it was absent in the natural isolates. This finding indicated resolution of trade-offs, i.e., mitigation of trade-offs over evolutionary history, probably through accumulation of compensatory mutations. In the deletion collection, organizational genes showed AP, suggesting ancient resolutions of trade-offs in the basic cellular pathways. We find abundant AP in the segregants, greater than estimated in the deletion collection or observed in previous studies, with IRA2, a negative regulator of the Ras/PKA signaling pathway, showing trade-offs across diverse environments. Additionally, IRA2 and several other Ras/PKA pathway genes showed balancing selection in isolates of S. cerevisiae and S. paradoxus, indicating that multiple alleles maintain AP in this pathway in natural populations. We propose that during AP resolution, retaining the ability to vary signaling pathways such as Ras/PKA, may provide organisms with phenotypic flexibility. However, with increasing organismal complexity AP resolution may become difficult. A partial resolution of AP could manifest as complex human diseases, and the inability to resolve AP may play a role in speciation. Our findings suggest that testing a universal phenomenon like AP across multiple experimental systems may elucidate mechanisms underlying its regulation and evolution. Genetics Society of America 2015-02-23 /pmc/articles/PMC4426359/ /pubmed/25711830 http://dx.doi.org/10.1534/g3.115.017020 Text en Copyright © 2015 Yadav et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Yadav, Anupama
Radhakrishnan, Aparna
Bhanot, Gyan
Sinha, Himanshu
Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation
title Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation
title_full Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation
title_fullStr Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation
title_full_unstemmed Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation
title_short Differential Regulation of Antagonistic Pleiotropy in Synthetic and Natural Populations Suggests Its Role in Adaptation
title_sort differential regulation of antagonistic pleiotropy in synthetic and natural populations suggests its role in adaptation
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426359/
https://www.ncbi.nlm.nih.gov/pubmed/25711830
http://dx.doi.org/10.1534/g3.115.017020
work_keys_str_mv AT yadavanupama differentialregulationofantagonisticpleiotropyinsyntheticandnaturalpopulationssuggestsitsroleinadaptation
AT radhakrishnanaparna differentialregulationofantagonisticpleiotropyinsyntheticandnaturalpopulationssuggestsitsroleinadaptation
AT bhanotgyan differentialregulationofantagonisticpleiotropyinsyntheticandnaturalpopulationssuggestsitsroleinadaptation
AT sinhahimanshu differentialregulationofantagonisticpleiotropyinsyntheticandnaturalpopulationssuggestsitsroleinadaptation