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Highlights: [•] Two novel introns are inserted in AGT from selected ray-finned fishes. [•] AGT is conserved on same syntenic fragment from 500 MY. [•] AGT became non-inhibitory from inhibitory serpin via RCL mutations. [•] AGT has 690 variants in 1092 human genomes from 14 populations. [•] 121 missense variants identified in human AGT protein with 32 deleterious mutants. [ABSTRACT FROM AUTHOR]

The recombination-activating genes (RAGs) encode for V(D)J recombinases responsible for rearrangements of antigen-receptor genes during T and B cell development, and RAG expression is known to correlate strictly with the process of rearrangement. There have been several studies of RAG1 illustrating biochemical, physiological and immunological properties. Hitherto, there are limited studies on RAG1 focusing molecular phylogenetic analyses, evolutionary traits, and genetic variants in human populations. Hence, there is a need of a comprehensive study on this topic. In the current report, we have shed light into insights of evolutionary traits and genetic variants of human RAG1 gene using 1092 genomes from human populations. Syntenic analyses revealed that two RAG genes are physically linked and conserved on the same locus in head-to-head orientation from sea urchin to human for about 550 MY. Spliceosomal introns have been in invaded in fishes and sea urchin, whereas gene structures of RAG1 gene from tetrapods remained single exon architecture. We compiled 751 genetic variants in human RAG1 gene using 1092 human genomes; where major stockholders of variant classes are 79% single nucleotide polymorphisms (SNPs), 12.2% somatic single nucleotide variants (somatic SNVs) and 6.8% deletion. Out of 267 missense variants, 140 are deleterious mutations. We identified 284 non-coding variants with 94% regulatory in nature. [ABSTRACT FROM AUTHOR]

C1 inhibitor (C1IN) is a multi-facet serine protease inhibitor in the plasma cascades, inhibiting several proteases, notably, regulates both complement and contact system activation. Despite huge advancements in the understanding of C1IN based on biochemical properties and its roles in the plasma cascades, the phylogenetic history of C1IN remains uncharacterized. To date, there is no comprehensive study illustrating the phylogenetic history of C1IN. Herein, we explored phylogenetic history of C1IN gene in vertebrates. Fishes have C1IN with two immunoglobulin like domains attached in the N-terminal region. The RCL regions of CIIN from fishes and tetrapod genomes have variations at the positions P2 and P1'. Gene structures of C1IN gene from selected ray-finned fishes varied in the Ig domain region with creation of novel intron splitting exon Im2 into Im2a and Im2b. This intron is limited to ray-finned fishes with genome size reduced below 1 Gb. Hence, we suggest that genome compaction and associated double-strand break repairs are behind this intron gain. This study reveals the evolutionary history of C1IN and confirmed that this gene remains the same locus for ~450 MY in 52 vertebrates analysed, but it is not found in frogs and lampreys. [ABSTRACT FROM AUTHOR]

Highlights: [•] ATIII possesses additional intron 262c is maintained in ray-finned fishes, but lost in other vertebrates. [•] ATIII is maintained in same genomic loci with few changes in fishes. [•] ATIII has 1997 variants in 1092 human genomes from 14 populations. [•] Three top variation classes are 76.2% SNPs, 11.8% deletions and 8.1% insertions. [•] There are 63 missense variants of human ATIII causes change in amino acids. [ABSTRACT FROM AUTHOR]