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PreprintCited by 2Developmental Biology and Gene RegulationCellular transport and secretionNeurogenesis and neuroplasticity mechanisms

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Conserved exchange of paralog proteins during neuronal differentiation

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Di Fraia, Domenico, Anitei, Mihaela, Mackmull, Marie-Therese, Parca, Luca, Behrendt, Laura, Andres-Pons, Amparo, Gilmour, Darren, Citterich, Manuela Helmer, Kaether, Christoph, Beck, Martin, Ori, Alessandro·2021·Life Science Alliance
DOI 10.1101/2021.07.22.453347PMC PMC8917807

Preprint — published as 10.26508/lsa.202201397 · Paper page

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Abstract

Gene duplication enables the emergence of new functions by lowering the general evolutionary pressure. Previous studies have highlighted the role of specific paralog genes during cell differentiation, e.g., in chromatin remodeling complexes. It remains unexplored whether similar mechanisms extend to other biological functions and whether the regulation of paralog genes is conserved across species. Here, we analyze the expression of paralogs across human tissues, during development and neuronal differentiation in fish, rodents and humans. While ~80% of paralog genes are co-regulated, a subset of paralogs shows divergent expression profiles, contributing to variability of protein complexes. We identify 78 substitutions of paralog pairs that occur during neuronal differentiation and are conserved across species. Among these, we highlight a substitution between the paralogs SEC23A and SEC23B subunits of the COPII complex. Altering the ratio between these two proteins via RNAi-mediated knockdown is sufficient to influence neuron differentiation. We propose that remodeling of the vesicular transport system via paralog substitutions is an evolutionary conserved mechanism enabling neuronal differentiation.

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Metadata

Authors
Di Fraia, D., Anitei, M., Mackmull, M.-T., Parca, L., Behrendt, L., Andres-Pons, A., Gilmour, D., Citterich, M. H., Kaether, C., Beck, M., & Ori, A.
Affiliations
  • Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
  • ETH Zurich (CH)
  • University of Rome Tor Vergata (IT)
  • University of Zurich (CH)
  • Max Planck Institute of Biophysics (DE)
ORCID
Venue
Life Science Alliance
Publisher
openRxiv
Published
2021-07-23
Volume
5
Issue
6
Pages
e202201397-e202201397
ISSN
2575-1077 (ISSN-L)
DOI
10.1101/2021.07.22.453347
PMC
PMC8917807
OpenAlex
W4226086748
Cited by
2
References
1
Citations by year
2026: 2
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Life Science Alliance (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
  • ETH Zürich Research Collection
Funders
  • European Molecular Biology Laboratory
  • Chan Zuckerberg Initiative
  • Australian Government
  • Deutsche Forschungsgemeinschaft (KA1751/8-1, GRK 2155, 2019_A79)
  • Associazione Italiana per la Ricerca sul Cancro (ig23539)
  • Leibniz-Gemeinschaft (GRK 2155, 2019_A79)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
gene duplication, neuronal differentiation, SEC23A, SEC23B, COPII complex, vesicle trafficking, co-regulation, evolutionary conservation, chromatin remodeling, RNAi knockdown
MeSH terms
Animals, Biological Evolution, Gene Duplication

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