SPHINGOMYELINASE D EVOLUTIION IN BROWN SPIDER VENOMS

棕色蜘蛛属是臭名昭著的叮咬，造成严重的皮肤坏死病变。鞘磷脂酶D已在棕色隐居L.隐退，作为这些病变形成的主要因素。这种酶在动物王国的其他地方都不存在。然而，它在一些细菌物种中表达为毒素。全世界大约有100种Loxosceles。只有少数物种的毒液被描述过，但有临床证据表明，许多地理分布广泛的物种的叮咬能够导致坏死。具有这种酶的物种的范围尚不清楚。这项拟议的研究有三个主要目标：（1）确定鞘磷脂酶D活性在Loxosceles属内以及在近亲中的系统发育分布，（2）研究该酶的分子进化以区分该谱系中鞘磷脂酶D起源机制的竞争假说，（3）比较刺角象与不含鞘磷脂酶D的近缘种之间毒液对各种昆虫猎物（它们的天然生物学作用中推测的毒液的主要靶）的作用。总之，实现这些目标将使我们了解进化起源的时间和情况，以及鞘磷脂酶D的分布和多样性，鞘磷脂酶D是一种对人类有毒的罕见酶。

Brown spiders in the genus Loxosceles are notorious for bites that cause severe dermonecrotic lesions. Sphingomyelinase D has been identified within the brown recluse, L. reclusa, as a major factor in the formation of these lesions. This enzyme is not known to exist anywhere else in the animal kingdom. However, it is expressed as a toxin in a few bacterial species. There are roughly 100 species of Loxosceles distributed worldwide. The venoms of only a few species have been described, but there is clinical evidence that bites from many widely geographically distributed species are capable of causing necrosis. The range of species that have this enzyme is not known. This proposed research has three main objectives: (1) to determine the phylogenetic distribution of sphingomyelinase D activity within the genus Loxosceles, and among close relatives, (2) to study the molecular evolution of this enzyme to distinguish among competing hypothesis of the mechanism of origin of sphingomyelinase D in this lineage, and (3) to compare the effects of venom on various insect prey (their presumed primary targets of venom in it's natural biological role) between Loxosceles and close relatives that do not have sphingomyelinase D. Together, achieving these objectives will inform our understanding of the timing and circumstances of evolutionary origin, and the distribution and diversity of the enzyme sphingomyelinase D, a rare enzyme that is toxic to humans.