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Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain

Changes in regulatory networks generate materials for evolution to create phenotypic diversity. For transcription networks, multiple studies have shown that alterations in binding sites of cis-regulatory elements correlate well with the gain or loss of specific features of the body plan. Less is kno...

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Autores principales: Onal, Pinar, Gunasinghe, Himari Imaya, Umezawa, Kristaley Yui, Zheng, Michael, Ling, Jia, Azeez, Leen, Dalmeus, Anecine, Tazin, Tasmima, Small, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136501/
https://www.ncbi.nlm.nih.gov/pubmed/33599280
http://dx.doi.org/10.1093/molbev/msab051
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author Onal, Pinar
Gunasinghe, Himari Imaya
Umezawa, Kristaley Yui
Zheng, Michael
Ling, Jia
Azeez, Leen
Dalmeus, Anecine
Tazin, Tasmima
Small, Stephen
author_facet Onal, Pinar
Gunasinghe, Himari Imaya
Umezawa, Kristaley Yui
Zheng, Michael
Ling, Jia
Azeez, Leen
Dalmeus, Anecine
Tazin, Tasmima
Small, Stephen
author_sort Onal, Pinar
collection PubMed
description Changes in regulatory networks generate materials for evolution to create phenotypic diversity. For transcription networks, multiple studies have shown that alterations in binding sites of cis-regulatory elements correlate well with the gain or loss of specific features of the body plan. Less is known about alterations in the amino acid sequences of the transcription factors (TFs) that bind these elements. Here we study the evolution of Bicoid (Bcd), a homeodomain (HD) protein that is critical for anterior embryo patterning in Drosophila. The ancestor of Bcd (AncBcd) emerged after a duplication of a Zerknullt (Zen)-like ancestral protein (AncZB) in a suborder of flies. AncBcd diverged from AncZB, gaining novel transcriptional and translational activities. We focus on the evolution of the HD of AncBcd, which binds to DNA and RNA, and is comprised of four subdomains: an N-terminal arm (NT) and three helices; H1, H2, and Recognition Helix (RH). Using chimeras of subdomains and gene rescue assays in Drosophila, we show that robust patterning activity of the Bcd HD (high frequency rescue to adulthood) is achieved only when amino acid substitutions in three separate subdomains (NT, H1, and RH) are combined. Other combinations of subdomains also yield full rescue, but with lower penetrance, suggesting alternative suboptimal activities. Our results suggest a multistep pathway for the evolution of the Bcd HD that involved intermediate HD sequences with suboptimal activities, which constrained and enabled further evolutionary changes. They also demonstrate critical epistatic forces that contribute to the robust function of a DNA-binding domain.
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spelling pubmed-81365012021-05-25 Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain Onal, Pinar Gunasinghe, Himari Imaya Umezawa, Kristaley Yui Zheng, Michael Ling, Jia Azeez, Leen Dalmeus, Anecine Tazin, Tasmima Small, Stephen Mol Biol Evol Fast Track Changes in regulatory networks generate materials for evolution to create phenotypic diversity. For transcription networks, multiple studies have shown that alterations in binding sites of cis-regulatory elements correlate well with the gain or loss of specific features of the body plan. Less is known about alterations in the amino acid sequences of the transcription factors (TFs) that bind these elements. Here we study the evolution of Bicoid (Bcd), a homeodomain (HD) protein that is critical for anterior embryo patterning in Drosophila. The ancestor of Bcd (AncBcd) emerged after a duplication of a Zerknullt (Zen)-like ancestral protein (AncZB) in a suborder of flies. AncBcd diverged from AncZB, gaining novel transcriptional and translational activities. We focus on the evolution of the HD of AncBcd, which binds to DNA and RNA, and is comprised of four subdomains: an N-terminal arm (NT) and three helices; H1, H2, and Recognition Helix (RH). Using chimeras of subdomains and gene rescue assays in Drosophila, we show that robust patterning activity of the Bcd HD (high frequency rescue to adulthood) is achieved only when amino acid substitutions in three separate subdomains (NT, H1, and RH) are combined. Other combinations of subdomains also yield full rescue, but with lower penetrance, suggesting alternative suboptimal activities. Our results suggest a multistep pathway for the evolution of the Bcd HD that involved intermediate HD sequences with suboptimal activities, which constrained and enabled further evolutionary changes. They also demonstrate critical epistatic forces that contribute to the robust function of a DNA-binding domain. Oxford University Press 2021-02-18 /pmc/articles/PMC8136501/ /pubmed/33599280 http://dx.doi.org/10.1093/molbev/msab051 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Fast Track
Onal, Pinar
Gunasinghe, Himari Imaya
Umezawa, Kristaley Yui
Zheng, Michael
Ling, Jia
Azeez, Leen
Dalmeus, Anecine
Tazin, Tasmima
Small, Stephen
Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
title Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
title_full Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
title_fullStr Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
title_full_unstemmed Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
title_short Suboptimal Intermediates Underlie Evolution of the Bicoid Homeodomain
title_sort suboptimal intermediates underlie evolution of the bicoid homeodomain
topic Fast Track
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136501/
https://www.ncbi.nlm.nih.gov/pubmed/33599280
http://dx.doi.org/10.1093/molbev/msab051
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