TY - JOUR T1 - Conserved exchange of paralog proteins during neuronal differentiation JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201397 VL - 5 IS - 6 SP - e202201397 AU - Domenico Di Fraia AU - Mihaela Anitei AU - Marie-Therese Mackmull AU - Luca Parca AU - Laura Behrendt AU - Amparo Andres-Pons AU - Darren Gilmour AU - Manuela Helmer Citterich AU - Christoph Kaether AU - Martin Beck AU - Alessandro Ori‬‬ Y1 - 2022/06/01 UR - https://www.life-science-alliance.org/content/5/6/e202201397.abstract N2 - Gene duplication enables the emergence of new functions by lowering the evolutionary pressure that is posed on the ancestral genes. Previous studies have highlighted the role of specific paralog genes during cell differentiation, for example, 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. Whereas ∼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 members of the COPII complex. Altering the ratio between these two genes 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. ER -