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Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoiddependent axial patterning in metazoans

Sobreira, Tiago J. P. and Marlétaz, Ferdinand and Simões-Costa, Marcos and Schechtman, Deborah and Pereira, Alexandre C. and Brunet, Frédéric and Sweeney, Sarah and Pani, Ariel and Aronowicz, Jochanan and Lowe, Christopher J. and Davidson, Bradley and Laudet, Vincent and Schubert, Michael and de Oliveira, Paulo S. L. and Xavier-Neto, José and Bronner, Marianne E. (2011) Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoiddependent axial patterning in metazoans. Proceedings of the National Academy of Sciences of the United States of America, 108 (1). pp. 226-231. ISSN 0027-8424. https://resolver.caltech.edu/CaltechAUTHORS:20110222-134006824

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Abstract

Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1011223108DOIUNSPECIFIED
http://www.pnas.org/content/108/1/226PublisherUNSPECIFIED
Additional Information:© 2011 National Academy of Sciences. Edited by John Gerhart, University of California, Berkeley, CA, and approved November 10, 2010 (received for review August 17, 2010). Published online before print December 17, 2010. We thank Gérard Benoit, Tiago Pereira, Linda Z. Holland, and Nicholas D. Holland for critical reading of the manuscript. We are indebted to the Faculty of Medicine of the University of São Paulo for access to its high-performance computing cluster. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo Grant 06/50843-0 (to J.X.-N.), by funds from Agence Nationale de Recherche (ANR-07-BLAN-0038 and ANR-09-BLAN-0262-02), Centre National de la Recherche Scientifique, and Ministere de l’Education Nationale de la Recherche et de Technologie (to M.S.), and by the Consortium for Research into Nuclear Receptors in Development and Aging (CRESCENDO), a European Union Integrated Project of FP6. M.S.-C. was supported by a travel fellowship from the Company of Biologists. Author contributions: M.S. and J.X.-N. designed research; T.J.P.S., F.M., M.S.-C., D.S., F.B., S.S., A.P., J.A., C.J.L., B.D., P.S.L.d.O., M.S., and J.X.-N. performed research; D.S., C.J.L., B.D., M.B., and P.S.L.d.O. contributed new reagents/analytic tools; T.J.P.S., F.M., M.S.-C., D.S., A.C.P., F.B., S.S., A.P., J.A., C.J.L., B.D., V.L., P.S.L.d.O., M.S., and J.X.-N. analyzed data; and T.J.P.S., F.M., D.S., B.D., V.L., M.B., P.S.L.d.O., M.S., and J.X.-N. wrote the paper.
Funders:
Funding AgencyGrant Number
Fundação de Amparo à Pesquisa do Estado de São Paulo06/50843-0
Agence Nationale de RechercheANR- 07-BLAN-0038
Agence Nationale de RechercheANR-09-BLAN-0262-02
Centre National de la Recherche ScientifiqueUNSPECIFIED
Ministere de l’Education Nationale de la Recherche et de TechnologieUNSPECIFIED
Consortium for Research into Nuclear Receptors in Development and Aging (CRESCENDO)UNSPECIFIED
Company of BiologistsUNSPECIFIED
Subject Keywords:Aldehyde dehydrogenase phylogeny; Branchiostoma floridae; Ciona intestinalis versus Ciona savignyi; evolution of retinoic acid signaling; origins of morphogen-dependent signaling
Issue or Number:1
Record Number:CaltechAUTHORS:20110222-134006824
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110222-134006824
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:22431
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:22 Feb 2011 23:15
Last Modified:03 Oct 2019 02:37

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