Molecular evolution of α-latrotoxin, the exceptionally potent vertebrate neurotoxin in black widow spider venom.
Molecular evolution of α-latrotoxin, the exceptionally potent vertebrate neurotoxin in black widow spider venom.
复制标题
DOI：
10.1093/molbev/mst011
复制
发表时间：
2013-05
影响因子：
10.7
通讯作者：
Hayashi CY
中科院分区：
文献类型：
--
作者：
Garb JE;Hayashi CY
黑寡妇蜘蛛（Latrodectus属的成员）因其强大的神经毒性毒液而被广泛恐惧。α-Latrotoxin是脊椎动物特有的毒素，负责黑寡妇毒液的戏剧性影响。这种毒素的进化是神秘的，因为只有两个α-latrotoxin序列是已知的。在这项研究中，104 kb的α-latrotoxin序列及其同源物的特点，从一个物种的Latrodectus的多样性，脂肪和寄生虫的代表，建立广泛分布的latrotoxins在巨大的多样性蜘蛛科球蛛。在黑寡妇种属中，α-latrotoxin显示≥94%的核苷酸同一性和变异性，与纯化选择一致。多密码子和分支特异性估计的非同义/同义取代率比也表明，纯化选择的历史很长，已经在Latrodectus和Steatoda中对α-latrotoxin起作用。然而，α-latrotoxin在这些属之间的氨基酸序列是高度差异的，68.7%的蛋白质差异涉及非保守取代，其生理化学性质和特定密码子的正选择证据，以及沿着α-latrotoxin的Latrodectus分支的非同义取代率升高。这种变异可能解释了红背蜘蛛L。hasselti，抗蛇毒血清在治疗咬伤从其他Latrodectus物种，和较弱的神经毒性症状相关的脂肪和寄生虫叮咬。对α-latrotoxin的长期纯化选择表明其在黑寡妇毒液中的功能重要性，即使脊椎动物是它们饮食的一小部分。Latrodectus和Steatoda α-latrotoxin之间的较大差异及其与无脊椎动物特异性latrotoxins的关系表明，α-latrotoxin向脊椎动物毒性增加的方向转变，与寡妇蜘蛛的进化一致。
Black widow spiders (members of the genus Latrodectus) are widely feared because of their potent neurotoxic venom. α-Latrotoxin is the vertebrate-specific toxin responsible for the dramatic effects of black widow envenomation. The evolution of this toxin is enigmatic because only two α-latrotoxin sequences are known. In this study, ∼4 kb α-latrotoxin sequences and their homologs were characterized from a diversity of Latrodectus species, and representatives of Steatoda and Parasteatoda, establishing the wide distribution of latrotoxins across the mega-diverse spider family Theridiidae. Across black widow species, α-latrotoxin shows ≥94% nucleotide identity and variability consistent with purifying selection. Multiple codon and branch-specific estimates of the nonsynonymous/synonymous substitution rate ratio also suggest a long history of purifying selection has acted on α-latrotoxin across Latrodectus and Steatoda. However, α-latrotoxin is highly divergent in amino acid sequence between these genera, with 68.7% of protein differences involving non-conservative substitutions, evidence for positive selection on its physiochemical properties and particular codons, and an elevated rate of nonsynonymous substitutions along α-latrotoxin’s Latrodectus branch. Such variation likely explains the efficacy of red-back spider, L. hasselti, antivenom in treating bites from other Latrodectus species, and the weaker neurotoxic symptoms associated with Steatoda and Parasteatoda bites. Long-term purifying selection on α-latrotoxin indicates its functional importance in black widow venom, even though vertebrates are a small fraction of their diet. The greater differences between Latrodectus and Steatoda α-latrotoxin, and their relationships to invertebrate-specific latrotoxins, suggest a shift in α-latrotoxin toward increased vertebrate toxicity coincident with the evolution of widow spiders.
登录
查看更多内容
影响因子：
6.2
作者：
CLARK, RF;WETHERNKESTNER, S;GERKIN, R
通讯作者：
GERKIN, R
影响因子：
4.8
作者：
Dulubova, IE;Krasnoperov, VG;Usherwood, PNR
通讯作者：
Usherwood, PNR
影响因子：
9.2
作者：
Aminetzach, Yael T.;Srouji, John R.;Hoekstra, Hopi E.
通讯作者：
Hoekstra, Hopi E.
影响因子：
5.8
作者：
Graudins, Andis;Little, Michelle J.;Nicholson, Graham M.
通讯作者：
Nicholson, Graham M.
影响因子：
64.8
作者：
Fry, BG;Vidal, N;Kochva, E
通讯作者：
Kochva, E