Causes and Population-genetic Consequences of Molecular Variation

侧重于从分子和群体遗传学角度阐明进化机制 在各个层面上，这个项目涉及理论发展和实验工作的结合。 以系统发育比较的方式进行的。分子/细胞水平的焦点是 通过DNA复制、mRNA转录和蛋白质翻译产生的错误率约为50% 细菌和真核生物物种。这项工作试图检验漂移屏障假说，该假说 假设自然选择对任何性状所能达到的精炼程度是有限的 通过随机漂移的力量，并与有效种群规模成反比。 复制保真度的测量源于序列序列的长期集合中的突变积累 瓶颈复制线，然后是全基因组测序。新开发的方法 将产生对不适当的核糖核酸率更高的平行估计 出现在mRNAs中，错误的氨基酸被结合到蛋白质中，允许评估 在这两个级别上的错误传播之间是否存在负关联。 进化的种群遗传机制将通过一个项目来阐明 对该模型地理上分布广泛的分离株的5000个基因组进行测序 小型甲壳动物，以及数量较少的关键外类群物种。 结合有关重组的精细模式的信息，这项研究将揭示 在一个由大约60个种群组成的集合中，漂移、突变和重组的相对大小， 对其他物种的调查远远超出了这一范围。这将使对以下假设的检验成为可能 基因结构和基因组结构水平上的变异是由当地的 种群遗传环境。普氏杜氏菌系统也有独特的功能，以获得 对进化遗传学两大未解之谜的洞察：起源和长期 蛋白质编码基因内含子的作用及缺失的原因和后果 减数分裂重组。 与人类健康相关。因为突变是所有变异的来源 自然选择起作用，为病原体的出现提供燃料，是终极选择。 遗传疾病和癌症的原因，我们在复制保真度方面的工作对 不同的人类健康问题。因为转录和翻译错误会导致细胞 毒性和蛋白质聚集，在这些水平上的工作也具有重大的应用意义。 最后，5000基因组计划将首次揭示种群如何进化 特征由漂移、突变和重组的相对能力来定义，从而产生洞察力 研究推动所有物种对自然环境做出反应的效率和机制的因素 选择。水稻减数分裂产生的分子/细胞机制的阐明 需要受精的单倍体卵子转化为无性生殖的二倍体卵子的产量很高 这是可取的，因为它将打开在不同物种中克隆繁殖的可能性。

Focused on elucidating the mechanisms of evolution at the molecular and population-genetic levels, this project involves an integration of theory development and experimental work performed in a phylogenetic comparative manner. The molecular/cellular level focus is on the rate of error production via DNA replication, mRNA transcription, and protein translation in ~50 bacterial and eukaryotic species. This work seeks to test the drift-barrier hypothesis, which postulates that the level of refinement that natural selection can achieve with any trait is limited by the power of random drift and inversely proportional to the effective population size. Measures of replication-fidelity derive from mutation accumulation in long-term sets of serially bottlenecked replicate lines followed by whole-genome sequencing. Newly developed methods will yield parallel estimates of the much higher rates at which inappropriate ribonucleotides appear in mRNAs and erroneous amino acids are incorporated into proteins, allowing evaluation of whether negative associations exist between error propagation at these two levels. The population-genetic mechanisms of evolution will be clarified via a project to sequence 5000 genomes from geographically widespread isolates of the model microcrustacean Daphnia pulex, as well as from smaller numbers of key outgroup species. Combined with information on the fine-scaled pattern of recombination, this study will reveal the relative magnitudes of drift, mutation, and recombination in a collection of ~60 populations, a survey far beyond that for any other species. This will enable a test of the hypothesis that variation at the level of gene structure and genomic architecture is directly driven by the local population-genetic environment. The D. pulex system also has unique features for gaining insights into two major unsolved mysteries in evolutionary genetics: the origin and long-term effects of introns in protein-coding genes, and the causes and consequences of the loss of meiotic recombination. Relevance to human health. Because mutation is the source of all variation upon which natural selection acts, provides the fuel for the emergence of pathogens, and is the ultimate cause of genetic disorders and cancer, our work on replication fidelity has broad significance for diverse human-health issues. Because transcription and translation errors lead to cellular toxicity and protein aggregation, work at these levels also has significant applied implications. Finally, for the first time, the 5000 Genomes Project will reveal how population evolutionary features are defined by the relative power of drift, mutation and recombination, yielding insight into the factors driving the efficiencies and mechanisms by which all species respond to natural selection. Elucidation of the molecular/cellular mechanisms by which meiotic production of haploid eggs requiring fertilization is converted to ameiotic production of diploid eggs is highly desirable as it would open up possibilities of clonal propagation in diverse species.