Lineage-specific protein repeat expansions and contractions reveal malleable regions of immune genes

Abstract

Functional diversi cation, a higher evolutionary rate, and intense positive selection help a limited number of immune genes interact with many continuously evolving pathogens. Repeats in protein-coding regions are a well-known source of rapid functional diversi cation, adaptive variation, and evolutionary novelty.Repeats play a crucial role in biochemical functions like functional diversi cation of transcription regulation, protein kinases, cell adhesion, signaling pathways, morphogenesis, DNA repair, recombination, and RNA processing. Repeat length variation can change the associated protein's interaction, e cacy, and overall protein network. Repeats have an intrinsic unstable nature and can potentially evolve rapidly and expedite the acquisition of complex phenotypic traits and functions. Because of their ability to generate rapid, adaptive variations over short evolutionary distances, repeats are considered "tuning knobs." Repeat length variation in speci c genes, like RUNX2 and ALX4, is associated with morphological and physiological changes across vertebrates. Here we study repeat length variation as a potent source of species-speci c immune diversi cation across several clades of tetrapods. Moreover, we provide a clade-wise comprehensive list of immune genes with repeat types for future studies of morphological/evolutionary changes within species groups. We observe signi cant repeat length variation of FASLG in Rodentia and C1QC in Primates' contrasting species groups.

Terminal regions of a protein are a hotspot for low complexity regions and selection

“…The comparison of the GC content revealed that LCR-containing genes have a significantly higher %GC than genes without LCRs across the whole Tetrapoda clade (Wilcoxon test; p < 0.05). The result is consistent with previously published studies on specific gene sets [ 12 , 40 ]. A high %GC in LCR-containing genes suggests that GC-rich regions are prone to LCR formation.…”

“…Studies highlighting the major pathways and processes of protein LCRs are scarce and are limited to specific genes [ 24 , 40 , 53 ]. To evaluate the major pathways and biological processes of protein LCRs, we used gene enrichment analyses using ShinyGO 0.76 server [ 54 ] (electronic supplementary material, table S4).…”

“…Previous studies report the GC composition of genes containing repeats to be significantly higher than those without repeats [ 12 , 29 , 40 ]. These studies were limited to specific organisms, specifically defined gene sets or amino acid tandem repeats.…”

“…Even though some studies have focused on genome-wide patterns of LCRs across clades [ 4 , 12 , 40 ], most of the studies either focus on limited gene sets, specific diseases or limited species [ 23 , 41 , 42 ]. These focused studies provide a detailed mechanism of protein repeat function in particular species or gene sets.…”