• Tue. Feb 11th, 2025

The best nucleotide substitution model for reconstruction was identified using the Smart Model Selection (SMS) tool on the ATGC server [57] with the Subtree-Pruning-Regrafting (SPR) method for searching tree topologies and 100 bootstrapping replicates for the evaluation of node support

Byacusticavisual

Jan 21, 2025

The best nucleotide substitution model for reconstruction was identified using the Smart Model Selection (SMS) tool on the ATGC server [57] with the Subtree-Pruning-Regrafting (SPR) method for searching tree topologies and 100 bootstrapping replicates for the evaluation of node support. mechanisms in shaping the venoms of these cryptic kraits. In vitro venom recognition and in vivo neutralisation experiments revealed a strong negative impact of venom variability on the preclinical performance of commercial antivenoms. While the venom of was neutralised as per the manufacturers claim, performance against the venoms of and was poor, highlighting the need for regionally-effective antivenoms in India. Keywords: venom evolution, new krait species from India, antivenom therapy, venom proteomics, venom gland transcriptomics, Romulus krait 1. Introduction The Common Krait (venoms are used for the manufacture of commercial Indian polyvalent antivenoms. Several reports of fatal envenomings by other superficially similar species, which share a distribution range with (15 DSR) in Southeastern Pakistan and Western India (Rajasthan, Gujarat and Maharashtra). A subspecies of the Sind KraitWalls Sind Krait ((cyt as previously believed, but are genetically indistinguishable from the Sind krait (sp. nov.). Through the use of comparative venom proteomics and venom gland transcriptomics, we show that the significant compositional differences in the venoms of cryptic kraits in Southern and Western India likely result from post-genomic regulatory mechanisms. Further, with the help of in vivo experiments in the murine model, we show that the venoms of and are amongst the most potently toxic snake venoms in the country, being over 11 and 6 times more potent than that of envenomings. Thus, we highlight the importance of molecular phylogenetics in identifying clinically-important cryptic snake species and the pressing need for CFTR-Inhibitor-II the development of regionally-effective antivenoms in India to counter the dramatic inter and intraspecific venom variations. 2. Results To unravel the phylogenetic relationships and venom variation in cryptic kraits from Southern and Western India, we sampled scales, venoms, venom glands and physiological tissues from kraits with either 15- or 17-mid-body DSRs (Figure 1; Table S1). Open in a separate window Figure 1 The range distribution of spp. in Southern and Western India and SDS-PAGE profiles of their venoms. (A). Panel A of this figure shows the range distribution of (light brown) and (red), and their range overlaps (grey) in the Indian subcontinent. Isolated records of (light brown circles), along with sampling locations CFTR-Inhibitor-II (red circles) of venoms and venom glands have also been shown. (B). SDS-PAGE profiles of venom samples [(Rajasthan and Maharashtra), (Maharashtra) and (Karnataka)], along with the marker (M), are shown in panel B. 2.1. Phylogenetic Reconstructions Phylogenetic reconstructions of two mitochondrial markers provided fascinating insights into the evolution of kraits in the Indian subcontinent (Figure 2 and Figures S1CS3). The overall topology of phylogeny was in complete agreement with the previously reported multilocus species tree [12]. Consistent with the literature, was recovered as a sister lineage to (Bayesian Posterior GluN1 Probability (BPP): 1; bootstrap (BS): 95). Interestingly, sequences from the 17-mid-body scale row krait from Maharashtra were found in the same clade as from Pakistan (BPP: 1; BS: 100). Surprisingly, however, was found to be polyphyletic with four distinct clades (Figure 2 and Figures S1CS3). CFTR-Inhibitor-II The 15 DSR krait from Karnataka was found in a distinct clade to its counterparts from West Bengal and Maharashtra (BPP: 1; BS: 100). In contrast, the 15 DSR krait from Maharashtra was recovered as a sister lineage to from Pakistan (BPP: 0.85; BS: 66). This clearly suggests that the 15 DSR krait from Karnataka is likely to be a CFTR-Inhibitor-II genetically distinct species. Open in a separate window Figure 2 Bayesian phylogeny of species. This figure highlights the phylogenetic relationships between species in Asia. Distinct lineages of kraits of interest have been shown in uniquely coloured boxes. Branches with superior node support (BPP 0.95) are shown in thick black lines, and the BPP values for ND4 and cyt markers are indicated for the clades of interest. Branch lengths in the tree are scaled by the number of nucleotide substitutions per site. Photographs depicting the lateral view of and have also been shown. The estimation of evolutionary divergence between the mitochondrial sequences (ND4 and cyt sequences of the 17 DSR krait from Maharashtra and the from Pakistan.