The Expansion and Functional Diversification of the Mammalian Ribonuclease A Superfamily Epitomizes the Efficiency of Multigene Families at Generating Biological Novelty

Abstract

The ribonuclease (RNase) A superfamily is a vertebrate-specific gene family. Because of a massive expansion that occurred during the early mammalian evolution, extant mammals in general have much more RNase genes than nonmammalian vertebrates. Mammalian RNases have been associated with diverse physiological functions including digestion, cytotoxicity, angiogenesis, male reproduction, and host defense. However, it is still uncertain when their expansion occurred and how a wide array of functions arose during their evolution. To answer these questions, we generate a compendium of all RNase genes identified in 20 complete mammalian genomes including the platypus, Ornithorhynchus anatinus. Using this, we delineate 13 ancient RNase gene lineages that arose before the divergence between the monotreme and the other mammals (∼220 Ma). These 13 ancient gene lineages are differentially retained in the 20 mammals, and the rate of protein sequence evolution is highly variable among them, which suggest that they have undergone extensive functional diversification. In addition, we identify 22 episodes of recent expansion of RNase genes, many of which have signatures of adaptive functional differentiation. Exemplifying this, bursts of gene duplication occurred for the RNase1, RNase4, and RNase5 genes of the little brown bat (Myotis lucifugus), which might have contributed to the species’ effective defense against heavier pathogen loads caused by its communal roosting behavior. Our study illustrates how host-defense systems can generate new functions efficiently by employing a multigene family, which is crucial for a host organism to adapt to its ever-changing pathogen environment.

Evolution of Digestive Enzymes and RNASE1 Provides Insights into Dietary Switch of Cetaceans

“…Of these, 46 sequences were newly identified from 26 mammalian genomes, including 23 species first reported and three species (cow, giant panda, and African elephant) corrected from Goo and Cho (2013) (supplementary data set and supplementary table S6, Supplementary Material online), whereas the rest of the 31 sequences were from 17 species, referenced from Goo and Cho (2013). Except for the platypus, other 42 mammalian species have at least one intact RNASE1 gene copy.…”

“…RNASE1 gene duplication has been found in many mammals with multi-compartmentalized stomachs, such as ruminants (e.g., cows, sheep, and camels) (Kleineidam et al 1999; Breukelman et al 2001), and species with ruminant-like or cecal digestions (e.g., leaf-eating colobines and elephants) (Zhang et al 2002; Yu et al 2010; Goo and Cho 2013; Zhou et al 2014). Gene duplication of RNASE1 is believed to be correlated with the plant-feeding adaptation of foregut-fermenting herbivores (Liu et al 2014), and ruminant artiodactyls have considerably higher concentrations of pancreatic RNASE1 than other mammals (Zhang 2006).…”

Three decades of research on angiogenin: a review and perspective

“…Analyses of complete or nearly complete mammalian genomes indicated the absence of ANG in six mammalian species (gibbon, naked mole rat, guinea pig, dog, giant panda, and African elephant) [23]. Notably, evolutionary and structural feature analyses showed that the ANG family evolves and duplicates from early ANGlike genes in fish [20].…”

Eosinophil-associated Ribonuclease 11 Is a Macrophage Chemoattractant

“…Furthermore, the 5Ј putative promoter region of mEar 11 includes no consensus binding sites for Stat6 (62), as one would anticipate if this transcript was regulated directly (as opposed to indirectly) in response to IL-4 and/or IL-13. It will be interesting to explore this response further among the rodent and other species with Ear clusters (31,32) to define clearly the nature and molecular basis of this unusual response.…”