Subfunctionalized expression drives evolutionary retention of ribosomal protein paralogs Rps27 and Rps27l in vertebrates

Abstract

The formation of paralogs through gene duplication is a core evolutionary process. For paralogs that encode components of protein complexes such as the ribosome, a central question is whether they encode functionally distinct proteins, or whether they exist to maintain appropriate total expression of equivalent proteins. Here, we systematically tested evolutionary models of paralog function using the ribosomal protein paralogs Rps27 (eS27) and Rps27l (eS27L) as a case study. Evolutionary analysis suggests that Rps27 and Rps27l likely arose during whole-genome duplication(s) in a common vertebrate ancestor. We show that Rps27 and Rps27l have inversely correlated mRNA abundance across mouse cell types, with the highest Rps27 in lymphocytes and the highest Rps27l in mammary alveolar cells and hepatocytes. By endogenously tagging the Rps27 and Rps27l proteins, we demonstrate that Rps27- and Rps27l-ribosomes associate preferentially with different transcripts. Furthermore, murine Rps27 and Rps27l loss-of-function alleles are homozygous lethal at different developmental stages. However, strikingly, expressing Rps27 protein from the endogenous Rps27l locus or vice versa completely rescues loss-of-function lethality and yields mice with no detectable deficits. Together, these findings suggest that Rps27 and Rps27l are evolutionarily retained because their subfunctionalized expression patterns render both genes necessary to achieve the requisite total expression of two equivalent proteins across cell types. Our work represents the most in-depth characterization of a mammalian ribosomal protein paralog to date and highlights the importance of considering both protein function and expression when investigating paralogs.

The Cell Wall-Related Gene Families of Wheat (Triticum aestivum)

“…As the protein sequences would remain nearly the same, genes would likely group together regardless of species in tree clades, as occurred with the laccases. Poplar laccases showed different tissue expression patterns compared to Arabidopsis, suggesting the expression subfunctionalization of the gene family as poplar and Arabidopsis genes were together in clades of a tree rather than separate clades [72,97]. The laccase gene family between wheat, maize, rice, and Arabidopsis showed consistent clades with members in each clade (Supplemental File S1), just like poplar and Arabidopsis [97].…”

“…Dicot PAL genes use only phenylalanine as a substrate, but some grass PAL genes can use phenylalanine or tyrosine as a substrate. This may have led to multiple function and expression changes over time, explaining the large PP gene expansion, potentially expressing subfunctionalization and neofunctionalization [72,98,99]. Peroxidases were hypothesized to have increased numbers in plants to maintain a diverse set of promoters for different tissues and timing of expression and protein distribution associated with large and diverse projected activities in the plant, which could be neofunctionalization and/or expression subfunctionalization [94].…”

“…This has been illustrated in the Arabidopsis and rice monosaccharide transporter gene families [71]. In addition to partitioning multiple functions from one gene into two, neofunctionalized expression or subfunctionalized expression can occur through expression differences brought about by changes in the promoter regions of duplicated genes instead of the protein-coding region [72].…”

Identification of an immune-related metabolic gene signature to predict possible prognosis in endometrial cancer and reveals immune landscape feature

“…In lung cancer, STXBP1 was found to be down-regulated but was identified as a prognosis-related gene in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients [28,29]. RPS27L is a p53-repressible target [30]. In previous studies, it was reported to be downregulated in breast cancer [31] and CRC [32], which related with worse prognosis.…”

A germline PAF1 paralog complex ensures cell type-specific gene expression

“…While this broad textbook generalization overall aligns with our current knowledge of gene expression, examples of tissueand cell type-specific variants of core gene expression machineries have been identified in most animal model organisms, including mice, frogs, zebrafish, and fruit flies (Drosophila melanogaster). These machineries include paralogs of basal transcription factors [4][5][6][7][8][9][10][11][12] , RNA exporters 13,14 , ribosomal proteins [15][16][17] , and proteasome subunits 18 . The molecular function and developmental impact of such core gene expression machinery variants, however, remain underexplored.…”