SPHINGOMYELINASE D EVOLUTIION IN BROWN SPIDER VENOMS

褐色蜘蛛属是臭名昭著的咬伤，造成严重的皮肤坏死病变。鞘磷脂酶D已在褐隐士（L. reclusa）中被确定为形成这些病变的主要因素。这种酶在动物界的其他任何地方都不存在。然而，它在一些细菌物种中以毒素的形式表达。大约有100种loxoscele分布在世界各地。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引起坏死。拥有这种酶的物种范围尚不清楚。这项拟议的研究有三个主要目标：(1)确定鞘磷脂酶D在Loxosceles属内及其近亲间的系统发育分布；(2)研究该酶的分子进化，以区分鞘磷脂酶D在该谱系中起源机制的相互竞争的假说；(3)比较毒液对Loxosceles和近亲之间各种昆虫猎物（它们在其自然生物学作用中被认为是毒液的主要目标）的影响，这些目标的实现将使我们了解进化起源的时间和环境，以及鞘磷脂酶D（一种对人类有毒的罕见酶）的分布和多样性。

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.