Urochordate serpins Are Classified into Six Groups Encoded by Exon-Intron Structures, Microsynteny and Bayesian Phylogenetic Analyses

Abstract

Members of serpin superfamily are involved in wide array of cellular processes to control proteolytic activities of eukaryotic organisms. Vertebrate serpins are extensively studied and reported to be classified into six groups (V1-V6) based on gene structures. However, there is no study conducted for serpins in urochordates (the closest living invertebrates related to vertebrates) to date. To unravel further the phylogenetic history of serpin genes, we characterized serpin genes from two urochordates (Ciona intestinalis and Ciona savignyi). There are 11 and 5 serpins in the C. intestinalis and C. savignyi, respectively. The exon/intron structures and genomic locus comparisons together with sequence phylogenetic analysis, suggested that urochordate serpins are classified into six groups (U1-U6), different from six groups (V1-V6) of vertebrate serpins. Human α1-antitrypsin shared lower sequence identities and similarities with urochordates serpins ranged from 14-29% and 30-49%, respectively. Based on protein sequences, genes and genomic architectures, we conclude that these two urochordates do not contain a single copy of genuine ortholog of the vertebrate serpins.

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“…However, another study depicted six different groups of urochordate serpins, based on intronencoded classification system, which markedly differs from vertebrates six groups (Kumar & Bhandari 2014). Gene structures of heparin cofactor II (HCII/SERPIND1) are variable in fishes with a novel intron gain at the position 241c, but this gene is nested in the large intron of phosphatidylinositol 4-Kinase (PIK4CA) gene for ~500 MYA (Kumar et al 2014a).…”

“…Interestingly, the RCL of AGT protein is inhibitory in lampreys and evolved to become non-inhibitory in human over a period of 500 MY (Kumar et al 2014d). Kumar et al (2014) also detected 690 AGT variants by analyzing 1092 human genomes with the top three variation classes belonging to single nucleotide polymorphisms (SNPs, 89.7%), somatic SNVs (5.2%) and deletion (2.9%) (Kumar et al 2014d). Furthermore, 121 missense variants of AGT including 32 statistically deleterious variants were deciphered (Kumar et al 2014d).…”

“…Some serpins have signals for sub-cellular localization at the C-terminal end and they have been involved in the secretory pathway. It is not just limited to vertebrate serpins and several examples exists in invertebrates such as in some urochordate serpins (Kumar & Bhandari 2014).…”

“…The RCL regions of C1IN/SERPING1 have variations at the positions P2 and P1' from fishes and tetrapods Gene structures of C1IN/SERPING1 from selected ray-finned fishes varied in the Ig domain region with the insertion of a novel intron splitting exon Im2 into Im2a and Im2b (Kumar et al 2014b). Kumar et al (2014) depicted that C1IN/SERPING1 gene has remained on the same locus for ~450 MY in 52 vertebrates, but it is missing in frogs and lampreys (Kumar et al 2014b).…”

“…Intron-exon and higher sequence similarities were maintained in serpins of a particular lineage such as in vertebrates (Figure 2), urochordates (Kumar & Bhandari 2014) and within insects (Kumar et al 2014c). With several 1000 genomes being currently underway, this issue of gene structure pattern will be revisited within the next decade, when several new animal genomes will be available in the databases.…”