A mechanism of gene evolution generating mucin function

Abstract

How novel gene functions evolve is a fundamental question in biology. Mucin proteins, a functionally but not evolutionarily defined group of proteins, allow the study of convergent evolution of gene function. By analyzing the genomic variation of mucins across a wide range of mammalian genomes, we propose that exonic repeats and their copy number variation contribute substantially to the de novo evolution of new gene functions. By integrating bioinformatic, phylogenetic, proteomic, and immunohistochemical approaches, we identified 15 undescribed instances of evolutionary convergence, where novel mucins originated by gaining densely O-glycosylated exonic repeat domains. Our results suggest that secreted proteins rich in proline are natural precursors for acquiring mucin function. Our findings have broad implications for understanding the role of exonic repeats in the parallel evolution of new gene functions, especially those involving protein glycosylation.

Emergence of saliva protein genes in the secretory calcium-binding phosphoprotein (SCPP) locus and accelerated evolution in primates

“…SMR3A and SMR3B, along with PROL1 (also named OPRPN), comprise a group of salivary SCPP genes that code for proteins rich in proline and have a distinct phylogenetic history. We previously showed that these proteins, due to their richness in proline, have served as precursors for the de novo evolution of mucin function at various stages of the mammalian phylogeny [13]. Our current analysis confirmed that based on nucleotide sequence homology, SMR3A and SMR3B likely originated as duplicates of PROL1 [34].…”

TheMUC19gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection

“…Perhaps the largest knowledge gap in why the Denisovan-like haplotype of MUC19 would be under positive selection is determining its underlying function. Mucins are secreted glycoproteins responsible for the gel-like properties and the viscosity of the mucus [Pajic et al, 2022]. MUC19 is associated with gland function in humans, which can be important components of immune response, in particular its role in mucus formation in tracheal submucosal glands in preventing pathogenic infections [Chen et al, 2004; Zhu et al, 2011; Reynolds et al, 2019].…”

First draft genome assembly and characterization of spongeHalisarca dujardiniireveals key components of basement membrane and broad repertoire of aggregation factors

“…A membrane-associated protein with a high level of glycosylation, Mucin, forms the backbone of mucus, covering the apical surface of epithelial cells in higher animals. Its functions are not limited to barrier function: mucins are able to regulate cell behavior and interactions 38,39 . The enzymes procollagen lysine hydroxylase, glycosyltransferase and peroxidasin have also been found to provide post-translational modifications of collagens (Supp.…”

“…A membrane-associated protein with a high level of glycosylation, Mucin, forms the backbone of mucus, covering the apical surface of epithelial cells in higher animals. Its functions are not limited to barrier function: mucins are able to regulate cell behavior and interactions 38,39 .…”