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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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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. |
format | Online Article Text |
id | pubmed-8136501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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