Biology subjects

S, S.

Publications and source records attributed to S, S..

23 records · Page 2Linked to original sources

bioRxiv2019

Phylogenetic, sequence and structural analysis of Insulin superfamily proteins reveals an indelible link between evolution and structure-function relationship

The insulin superfamily proteins (ISPs), in particular, insulin, IGFs and relaxins are key modulators of animal physiology. They are known to have evolved from the same ancestral gene and have diverged into proteins with varied sequences and distinct functions, but maintain a similar structural architecture stabilized by highly conserved disulphide bridges. A recent surge of sequence data and the structures of these proteins prompted a need for a comprehensive analysis which connects the evolution of these sequences in the light of available functional and structural information and their interaction with cognate receptors. This study reveals a) unusually high sequence conservation of IGFs (>90%), which has never been reported before. In fact, it was interesting to observe that the functional domains (excluding signal peptide) of human, horse, pig and Ords kangaroo rat are 100% identical. (b) an updated definition of the signature motif of the relaxin family (c) a non-canonical C-peptide cleavage site in a few killifish insulin sequences and so on. We also provide a structure-based rationale for such conservation by introducing a concept called binding partners imposed evolutionary constraints. Furthermore, the high conservation of IGFs appears to represent a classic case of resistance to sequence diversity exerted by physiologically important interactions with multiple partners. Furthermore, we propose a probable mechanism for C-peptide cleavage in killifish insulin sequences.

evolutionary biology↗

bioRxiv2019

Integrative taxonomy confirms the species status of the Himalayan langurs, Semnopithecus schistaceus Hodgson 1840

Taxonomy is replete with groups where the species identity and classification remain unresolved. One such group is the widely distributed Hanuman langur (Colobinae: Semnopithecus). For most part of the last century, Hanuman langur was considered to be a single species with multiple subspecies. Nevertheless, recent studies using an integrative taxonomy approach suggested that this taxon is a complex, with at least three species. However, these studies did not include the Himalayan population of the Hanuman langur whose taxonomic status remains unresolved. The Himalayan population of Hanuman langurs have been classified as a distinct species with multiple subspecies or have been subsumed into other species. These classification schemes are wholly based on morphological characters and which are sometimes insufficient to delimit different species. Here, we have integrated data from multiple sources viz. morphology, DNA, and ecology to resolve the taxonomy of the Himalayan langur and to understand its distribution limit. Our results with three lines of evidence corresponding to three different species concepts show that Himalayan langur is a distinct species from S. entellus of the plains. Additionally, these results did not show any support for splitting of the Himalayan langur into multiple subspecies. Our study supports the classification proposed by Hill (1939) and we recommend Semnopithecus schistaceus, Hodgson 1840 as species name for the Himalayan langur and subsume all the known subspecies into it.

evolutionary biology↗

bioRxiv2019

Computational prediction and analysis of very high risk single nucleotide polymorphisms in human cytochrome P450 oxidoreductase gene

Cytochrome P450 oxidoreductase (POR) is a highly polymorphic gene which is involved in metabolism of drugs and steroids through transfer of electron from NADPH to all CYP enzymes. In this study, we attempt to identify the very high risk single nucleotide polymorphisms in POR gene that would affect phenotype of the enzyme. The genetic variants in POR gene were retrieved from databases and analyzed with appropriate online computation tools. Very high risk non-synonymous SNPs were identified with 12 different sequence and structure homology based tools and evolutionary conservation tool (Consurf). Further the phenotype effect of the variant was assessed with MutPred2 and LigPlot. The very high risk non-coding variants were predicted with HaploReg V4 and RegulomeDB tools. The very high risk SNPs that may affect miRNA target sites were screened using PolymiRTs v3.0, miRNA SNP v2.0 and MirSNP. Among 4,601 variants in POR gene, 58 missense variants, 8 non-coding variants and three SNPs in miRNA target sites were found to be very high risk. These very high risk variants may regulate the expression and activity of cytochrome P450 oxidoreductase enzyme leading to differential drug and steroid metabolism by CYP enzymes.

genomics↗

bioRxiv2019

Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells

Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role of Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interact with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but might rather regulate other processes in the nucleoplasm. Summary blurbSox2 interacts with RNA-binding proteins and diverse RNAs

molecular biology↗

bioRxiv2018

Direct determination and differentiation of carbapenemases of A. baumannii from uncultured tracheal samples

The emergence of multiple carbapenemases and the consequent multi drug resistance in bacteria constitute a grave concern in the management of critical care patients and also in community acquired infections. Detection of carbapenamase activity helps to understand the possible mechanism(s) of carbapenem resistance in the microorganism. Identification of carbapenemases is currently being done by various phenotypic methods and molecular methods. However, innovative biochemical and spectrophotometric methods are desirable as they will be easy to perform, affordable and rapid. Recently a novel chromogenic method called CarbaNP test was introduced to screen for carbapenemases in clinical isolates of gram negative pathogens. We adopted this assay: (i) to detect the total carbapenemase activity (ii) to measure the relative rates of hydrolysis of imipenem by class A, B and D carbapenemases with inhibitors (iii) to confirm the genotype by PCR and (iv)for direct differential detection of various carbapenemases in uncultured clinical sample like tracheal aspirate. The study included 75 culture isolates and 153 purulent tracheal aspirates. All isolates were screened by our optimized protocol and also genotyped by PCR. This adopted assay showed good sensitivity and correlation with conventional phenotyping and genotyping. Our protocol offers the fastest way to identify the pathogen by PCR but also its carbapenemase profile directly from uncultured clinical samples in less than 4h. Our protocol is currently being validated on other types of clinical specimens in our laboratory.

microbiology↗