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At low concentrations, but without clear pharmacological significanceAird et al. BMC Genomics (2015) PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/17117591 16:Page 13 ofAEvolutionary Rate (dN/dS)r = 0.64 p = 0.1.CTL FX MPIII CRISP BPP MPII SP CTL PLA B GBL0.BEvolutionary Rate (dN/dS)1.3FTXr = 0.82 p = 0.1.MPPLALAO PLA0.CRISP LAO Kallikrein NGFAPAPDE0.HYAL NGF 5'NUC DPP IV VEGF0.1 10Cystatin HYAL10 103 105Transcript Abundance ( FPKM)Transcript Abundance (counts)Fig. 7 Data sets from two snake families show that more abundant venom proteins evolve more rapidly. Both panels show evolutionary rates, averaged by toxin class, as a function of abundance, using data from five crotaline species in three Old and New World genera (a), and the king cobra genome (re-analyzed from Fig. 5 in Vonk et al. [43]) (b). These results mirror the pairwise differences between P. PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16505107 elegans and P. flavoviridis shown in Fig. 6. In both cases, average evolutionary rates for the most abundant toxin classes tend to lie above dN/dS > 1, suggesting positive selection. Analyses for the two families are presented separately, because they vary greatly in toxin class composition and relative abundance of venom constituents. Significance of the associations was computed using Spearman's rank correlation. Abbreviations: 3FTX: 3-finger toxins, APA: Aminopeptidase A, BPP: bradykinin-potentiating peptide, GBL: galactose-binding lectin, CRISP: cysteine-rich secretory proteins, DPP: dipeptidylpeptidase IV, HYAL: hyaluronidase, NGF: nerve growth factor, 2-dioxaborolane 3-Fluoro-5-iodobromobenzene Cyclobutylboronic acid 4 VEGF: vascular endothelial growth factor (see additional abbreviations in Fig. 6)involved in venom formulation. Venoms are costly for snakes to produce [114]. Given that venom components can range in abundance by 3? orders (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-4,4-dimethylpentanoic acid of magnitude [42] (Fig. 5b), their cost to the snake likely also varies greatly, with more abundant components being more costly. Optimal foraging considerations suggest that snakes should invest in venom constituents in proportion (R)-1-(3-Chlorophenyl)ethan-1-ol to the benefit each of them provides. Therefore, variability in efficacy of the more abundant components will have the greatest fitness consequences for the snake, and those components should experience higher levels of selection. The higher evolutionary rates we observe in more abundant components are the evolutionary signature of this process. This also suggests that changes in venom component levels, rather than protein sequence-level changes, may be the most rapid and effective way for snakes to exploit new prey species.prefectural program to remove habus from densely inhabited areas. All animals, six males and two females, were adults, ranging from 82 to 150 cm total length (Table 1). Snakes were maintained at the Okinawa Prefectural Institute of Health and the Environment (OPIHE) after capture. Venoms were manually extracted into plastic beakers, transferred to cryovials, fast frozen on dry ice, and then stored at -30 until use.Removal of venom glandsFour days after venom extraction, one animal of each species was euthanized under pentobarbital anesthesia (>100 mg/kg), in accordance with OIST animal care protocols. Right and left venom glands and underlying skeletal muscle were excised, placed individually into 2 mL cryovials, flash frozen in liquid nitrogen, and stored at -80 until use.Transcriptomics Isolation of total mRNA from venom glands and first strand cDNA synthesisDeposition of data Sequences of genes confirmed by mass spectrometry were curated manually by comparison with data publicly available at NCBI GenBank, and d.