RT Journal Article
SR Electronic
T1 Conserved exchange of paralog proteins during neuronal differentiation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201397
DO 10.26508/lsa.202201397
VO 5
IS 6
A1 Domenico Di Fraia
A1 Mihaela Anitei
A1 Marie-Therese Mackmull
A1 Luca Parca
A1 Laura Behrendt
A1 Amparo Andres-Pons
A1 Darren Gilmour
A1 Manuela Helmer Citterich
A1 Christoph Kaether
A1 Martin Beck
A1 Alessandro Ori‬‬
YR 2022
UL https://www.life-science-alliance.org/content/5/6/e202201397.abstract
AB 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.