Molecular evolution of myotoxic phospholipases A2 from snake venom
Section snippets
Preface
Although snake venoms contain a number of bioactive proteins, phospholipase A2 (PLA2) isoforms constitute major toxic components. It is well known that snake venom PLA2s exhibit a variety of physiological activities in addition to intrinsic lipolytic action. From analysis of the cDNAs and genes encoding snake venom PLA2s, it became evident that they have evolved in an accelerated manner. Such accelerated evolution has rarely been known in general (ordinary) isozymes. Now it is thought that
Classification and amino acid sequences of snake venom PLA2s
PLA2 [EC 3.1.1.4] catalyzes the hydrolysis of the 2-acyl ester bond of 3-sn-phosphoglycerides with the requirement of Ca2+to produce 3-sn-lysophosphoglycerides and fatty acids. The amino acid sequences of over 200 PLA2s, in which about 170 are from snake venoms, had been determined up to 1997 (Danse et al., 1997). At present its number is still increasing. Most of them are classified into groups I and II based on the mode of disulfide pairings (Dufton and Hider, 1983). Group I PLA2s are found
Crystal structure of snake venom PLA2s
After the crystal structure of bovine pancreatic [Asp49]PLA2, which belongs to group I, was established by Dijkstra et al. (1981), those of group I [Asp49]PLA2s from the venoms of Naja naja atra (Scott et al., 1990), N. n. naja (Fremont et al., 1993), and Notechis s. scutatus (Westerlund et al., 1992), and of group II [Asp49]PLA2s from the venoms of Crotalus atrox (Brunie et al., 1985), Agkistrodon halys blomhoffii (Tomoo et al., 1994), T. flavoviridis (Suzuki et al., 1995), A. halys pallas (
Diverse physiological activities of snake venom PLA2s
Snake venom PLA2 isozymes are well known to exhibit a variety of physiological activities such as hemolysis (Kihara et al., 1992), myotoxicity (Gutierrez and Lomonte, 1997, Gopalakrishnakone et al., 1997), neurotoxicity (Bon, 1997, Gubensek et al., 1997, Fletcher and Rosenberg, 1997), anticoagulant activity (Evans and Kini, 1997), edema-inducing activity (Vishwanath et al., 1987, Wang and Teng, 1990, Liu et al., 1991, Tan et al., 1991, Yamaguchi et al., 2001), cardiotoxicity (Fletcher et al.,
Structures of the cDNAs and genes encoding venom PLA2 isozymes
Five cDNAs encoding T. flavoviridis (Tokunoshima) venom-gland PLA2 isozymes, PLA2, [Thr38]PLA2, PL-X′, BPI and BPII, were cloned and sequenced (Oda et al., 1990, Ogawa et al., 1992). It was clearly indicated by Northern blot analysis with these cDNAs and their 5′ or 3′ untranslated regions (UTRs) as probes that the mRNAs coding for these PLA2 isozymes are expressed only in the venom gland but not in other tissues such as heart, lung, liver, pancreas, kidneys, gall bladder, testis and ovaries (
Accelerated evolution of Crotalinae snake venom PLA2 isozyme genes
The evolutionary significance was noted for the nucleotide sequences of Crotalinae snake (T. flavoviridis, T. gramineus and T. okinavensis) venom PLA2 isozyme genes. Mathematical analysis was conducted for relevant pairs of PLA2 isozyme genes. The numbers of nucleotide substitutions per site (KN) for the noncoding regions, the numbers of nucleotide substitutions per synonymous site (KS), and the numbers of nucleotide substitutions per nonsynonymous site (KA) for the protein-coding regions were
Mechanism of accelerated evolution of snake venom PLA2 isozyme genes
A concept of accelerated evolution was led by several characteristics of the venom PLA2 isozyme genes: (1) the protein-coding regions, except for the signal sequence domain, are much more variable than the noncoding regions including introns, (2) the rates of nonsynonymous substitution are close to or greater than those of synonymous substitution in the protein-coding regions, and (3) the gene products exhibit diverse physiological activities. Two possibilities are considered for accelerated
Evolutionary relationships of Viperidae venom PLA2 isozymes
Phylogenetic trees were constructed for the nucleotide sequences of 11 Viperidae group II PLA2 cDNAs (Ogawa et al., 1995) according to the one-parameter method (Jukes and Cantor, 1969) and to the neighbor-joining algorithm (Saitou and Nei, 1987). A evolutionary tree constructed from the combined sequences of the 5′ and 3′ UTRs and the signal peptide-coding region is shown in Fig. 5. This tree shows that there are two groups, Crotalinae PLA2s and Viperinae PLA2s, which are evidently divided.
Interisland evolution of venom-gland PLA2 isozymes of T. flavoviridis snakes
T. flavoviridis snakes inhabit the southwestern islands of Japan: Amami-Oshima, Tokunoshima and Okinawa. Amami-Oshima is the northernmost and Tokunoshima island is 30 km south of Amami-Oshima. Okinawa island is located a further 120 km south of Tokunoshima island. These islands are thought to have been separated by eustacy (change in sea level) in the orogenic stage 1–2 million years ago (Hoshino, 1975). Since then, ancestral T. flavoviridis species in the former Okinawa continent were
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