Phylogeography of Verrucarum sand fly disease vectors

描述(由申请人提供)：在全球范围内，这种毁容的皮肤形式的利什曼病导致2000-4000万人感染病例，并仅通过受感染的血吸虫沙蝇的叮咬传播。利什曼病在整个新大陆热带地区是地方病，现在在农村、森林和郊区环境中明显增加。第二种由沙蝇传播的疾病，巴尔通氏杆菌病，是南美洲安第斯山脉的祸害，病例集中在秘鲁--它在未经治疗的病例中有很高的致死率&80%。目前的建议侧重于褐斑病属(Verrucarum Group)的28种沙蝇，其中至少包括17种已知或疑似一种或多种此类疾病的病媒。具体目的如下：(1)比较寻常疣菌群中分布最广的两个成员的种群遗传结构，它们分别是疣状丝虫(Bartonellosis载体)和Serrana(可能的皮肤利什曼病载体)，以便利用可变的线粒体基因序列(Cytb)来检测隐蔽物种和评估地理屏障和线性距离对遗传分化的相对重要性。(2)采用全证据方法--DNA测序、杂交和同工酶，研究形态上几乎相同的物种(6种城镇链霉菌和2种锯缘链霉菌)之间的遗传关系。(3)通过比较线粒体(12SrDNA，Col)和核基因(18SrDNA，28SrDNA，ITS2)的序列，推测Verrucarum属及相关亚属的分子系统发育。(4)利用所推断的系统发育来验证形态上定义的种、系、亚属和属的定义，并对它们进行单系性检验。(5)推断该类群的地理和生态群丛的演化史。(6)开发快速鉴定沙蝇类群的分子工具。这些目标的解决将提供对沙蝇种群遗传结构和地理隔离的影响的洞察。它将检验形态分类是否由系统发育历史证明是合理的。从生成的一套遗传图谱中，将有助于物种鉴定和物种真实性。一个大的和医学上重要的类群，Verrucarum的系统发育关系将被澄清。将建立一个更广泛的视角来研究褐藻属近400个物种之间的关系。更好地理解这些分析提供的分类和系统发育关系将直接导致对疾病风险的更现实的评估，并对环境影响对沙蝇进化的细微差别有新的见解。

DESCRIPTION (provided by the applicant): Globally, the disfiguring, cutaneous form of leishmaniasis produces 20-40 million human cases and is transmitted exclusively by the bite of infected phlebotomine sand flies. Leishmaniasis is endemic throughout the New World tropics, and it is now increasing noticeably in rural, forested and suburban settings. A second sand fly-vectored disease, bartonellosis, is a scourge of the South American Andes with cases concentrated in Peru--it has a high fatality ratio >80% in untreated cases. The current proposal focuses on the 28 sand fly species of the Verrucarum group (in the genus Lutzomyia), which includes at least 17 known or suspected vectors of one or more of these diseases. The specific aims are as follows: (1) To compare the population genetic structure of 2 of the most widely distributed members of the Verrucarum group, Lutzomyia verrucarum (bartonellosis vector) and Lutzomyia serrana (probable cutaneous leishmaniasis vector), in order to detect cryptic species and evaluate the relative significance of geographic barriers and linear distance to genetic differentiation using variable mitochondrial gene sequences (cytb). (2) To investigate genetic relatedness among morphologically almost identical species (6 species of the s. townsendi and 2 species of the s. serrana) using total evidence approaches--DNA sequences, hybridization and isoenzymes. (3) To infer a molecular phylogeny for species of the Verrucarum group and related subgenera, and genera, based on comparison of mitochondrial (12SrDNA, COl) and nuclear gene sequences (18SrDNA, 28SrDNA, and ITS2). (4) To use the inferred phylogeny for verifying morphologically defined species, series, subgenera, and genera definitions, by testing their monophyly. (5) To deduce the evolutionary history of geographical and ecological associations of this group of taxa. (6) To develop molecular tools for a rapid identification of sand fly taxa. Resolution of these aims will provide insights into sand fly population genetic structure, and effects of geographic isolation. It will test if morphological classifications are justified by phylogenetic history. From the suite of genetic profiles generated, species identification and species authenticity will be facilitated. The phylogenetic relationships of a large and medically important group, Verrucarum, will be clarified. A broader perspective to the relationships among the nearly 400 species in the genus Lutzomyia will be established. A better understanding of the taxonomic and phylogenetic relationships provided by these analyses will lead directly to more realistic assessments of disease risk and new insights into the nuances of environmental effects on sand fly evolution.