Phylogeography of Verrucarum sand fly disease vectors

描述（由申请方提供）：在全球范围内，毁容、皮肤形式的利什曼病产生了2000万至4000万例人类病例，仅通过受感染的白蛉叮咬传播。利什曼病是整个新大陆热带地区的地方病，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，巴尔通体病，是南美洲安第斯山脉的祸害，病例集中在秘鲁-在未经治疗的病例中，死亡率高达80%以上。目前的建议侧重于疣蝇属（Lutzomyia属）的28种白蛉，其中包括至少17种已知或怀疑的一种或多种疾病的载体。具体目的如下：（1）利用线粒体可变基因序列（cytb），比较疣鼻蚊（Lutzomyia verrucarum，巴尔通体病载体）和锯纹路蚊（Lutzomyia serrana，可能的皮肤利什曼病载体）这两种疣鼻蚊的种群遗传结构，以发现潜在种，并评价地理屏障和线性距离对遗传分化的相对意义。(2)为了研究形态上几乎相同的物种（6种）之间的遗传关系。Townsendi和2种S. serrana）使用全证据方法-DNA序列，杂交和同工酶。(3)根据线粒体（12 SrDNA，CO 1）和核基因（18 SrDNA，28 SrDNA和ITS 2）序列的比较，推断疣孢属及其相关亚属和属的分子遗传学。(4)通过检验单系性，使用推断的系统发生来验证形态学上定义的种、系、亚属和属的定义。(5)推断该类群的地理和生态关系的演化历史。(6)建立白蛉分类群快速鉴定的分子工具。这些目标的决议将提供深入了解白蛉种群遗传结构，地理隔离的影响。它将测试形态分类是否被系统发育史证明是合理的。根据所产生的一套基因图谱，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组，疣，系统发育关系将得到澄清。对近400种Lutzomyia的亲缘关系有了更广阔的认识。更好地了解这些分析提供的分类学和系统发育关系，将直接导致更现实的疾病风险评估和新的见解的细微差别，环境对白蛉进化的影响。

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.