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Conserved exchange of paralog proteins during neuronal differentiation

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 genes via RNAi-mediated knockdown is sufficient to influence the differentiation of immature neuron. We propose that remodeling of the vesicular transport system via paralog substitutions is an evolutionary conserved mechanism enabling neuronal differentiation.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Neuron

SUBMITTER: Emilio Cirri

LAB HEAD: Alessandro Ori

PROVIDER: PXD027387 | Pride | 2022-03-07

REPOSITORIES: Pride

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			Action	DRS
	201111_IH_Ori030_S01_si_Non_an1_Rep1_DIA_20201111145552.raw	Raw
	201111_IH_Ori030_S02_si_Non_an1_Rep2_DIA.raw	Raw
	201111_IH_Ori030_S03_si_Sec23a_an1_Rep1_DIA.raw	Raw
	201111_IH_Ori030_S04_si_Sec23a_an1_Rep2_DIA.raw	Raw
	201111_IH_Ori030_S05_si_Sec23b_an1_Rep1_DIA.raw	Raw

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Conserved exchange of paralog proteins during neuronal differentiation

Project description: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 eggNOG 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 genes via silencing-RNA knockdown was able to influence neuronal differentiation in different ways. We propose that remodeling of the vesicular transport system via paralog substitutions is an evolutionary conserved mechanism enabling neuronal differentiation.

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Conserved exchange of paralog proteins during neuronal differentiation

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