POPULATION GENETICS OF D SIMULANS AND D MELANOGASTER

描述：贝京博士的基本问题是什么样的自然选择 作用于DNA序列变异。当他在读研究生的时候，他发现 在这一重要的领域中，什么成为了最有价值的对比 问询。他发现，黑腹盘藻基因组的某些区域 经历低水平的交换也揭示了低水平的DNA 序列变异。他还表明，这不能用 这两个区域的变异率，如DNA的变异率 物种间的差异不随重组率的变化而变化。贝京博士 我意识到这种模式一定是由于 自然选择和连锁。从他最初发现的时候起， 已经有相当多的论文和研究项目致力于 关于哪种(或几种)自然选择是导致 巴斯蒂安博士发现的模式。 目前，主要的竞争者是搭便车模式，即 有益的突变席卷整个种群并消除变异 与有益突变部位紧密相连的区域，以及 背景选择模型，借此有害突变移除单倍型 有可能留下后代。在背景选择下 模型中，有害突变率对于一大块 连接的基因，以及许多，也许大多数，单倍型可能与 有害的突变。只有那些没有太多机会的部分 以可感知的频率分离变异，并且这一部分可能是 很小。 该应用程序仔细分析了测试这些模型的困难， 并回顾了衡量重组的问题性质和 突变率。博士开始的理由是，对于许多问题，最有用的 可以进行对比的是在果蝇模拟器中，它很可能是 影响重组率的外部因素较少(例如分离 反转)，而不是黑腹毛虫。 建议的核心是认真衡量同义词，并进行替换 两种动物基因组四个特征区域的多态 黑猩猩和类人猿。这些区域每个都有许多基因，这些基因具有 已经被测序，并且它们已经被表征为重组 在这两个物种中的比率。Begin博士预计，来自D.Simple的数据将在 特指将充分自信地揭示X的相对水平 和常染色体变异。在背景选择模式下，如果 有害突变是部分隐性的(很可能是真的)，那么 背景选择效果的大小应该更大 常染色体，而不是X连锁基因。连锁隐性基因拷贝 有害的突变最终不会在任何一种情况下发生 X或常染色体，但它们可以在常染色体上漂移到更高的频率 他们在多大程度上受到了隐性的保护。在搭便车的情况下 有利的突变，X连锁和X连锁之间预期的差异程度 常染色体基因取决于突变的显性：如果它们是 如果它们是X连锁的，那么它们更有可能修复；如果它们是X连锁的 相加，则X和常染色体应经历相同的速率 固定(因此是搭便车)；如果他们占主导地位，那么 常染色体应该会经历更大的影响。 另一个主要问题是，替换与静默的比率是如何 物种间的变异作为重组的函数而不同。一个 在这方面的关键观察是，仿生杜氏菌似乎 分离相当大的过量同义位点(即在蛋白质内 编码区但不影响氨基酸序列)变异，相对于 常染色体上的替换(即改变氨基酸)变异。D. SIMANS的这两个类别的变异略多一些，D。 X染色体上的黑腹鼠(这一比例在两个物种中是相同的)。 但在常染色体上，从比例上讲，D-Simans有更多的同义词 变异，要么给定黑素胃泌素水平，要么给予常染色体替代 在仿生杜鹃体内的水平。鉴于这一观察结果，贝京博士预计D. 模拟物在以下地区具有更高的比例或替代同义词 低复合的区域比高复合的区域低。 贝京博士希望对大约100个基因座(每个约1000个碱基)进行测序 每种14条线(每种7条来自非洲，7条来自非洲)。 这些数据还将揭示关于基因座之间变异的丰富信息 不同种类的多态，以及这种变异的方式 与分类群之间的分化相对应。

DESCRIPTION: Dr. Begun's basic question is what kind of natural selection is acting on DNA sequence variation. While a graduate student he discovered what has become the single most valuable contrast in this important area of inquiry. He found that regions of the D. melanogaster genome that experience low levels of crossing-over also reveal low levels of DNA sequence variation. He also showed that this could not be explained by variation in the rate of mutations in the two regions, as the rate of DNA divergence between species does not vary with recombination rate. Dr. Begun realized that this pattern must be due to some kind of interaction between natural selection and linkage. Since the time of his initial discoveries, quite a number of papers and research programs have been dedicated to the question of what kind (or kinds) of natural selection are the cause of the patterns that Dr. Begun discovered. At the moment, the principle contenders are the hitchhiking model, whereby beneficial mutations sweep through populations and remove variation from regions tightly linked to the site of the beneficial mutation, and the background selection model, whereby deleterious mutations remove haplotypes from having potential to leave descendants. Under the background selection model, the deleterious mutation rate may be quite high for a large block of linked genes, and so many, perhaps most, haplotypes may be linked to deleterious mutations. Only the fraction that are not have much chance of segregating variation at appreciable frequency, and this fraction may be quite small. The application carefully dissects the difficulties of testing these models, and it reviews the problematic nature of measuring recombination and mutation rates. Dr. Begun reasons that for many questions, the most useful contrasts that can be made are in Drosophila simulans which is likely to have less extraneous factors affecting recombination rates (e.g. segregating inversions) than does D. melanogaster. The core of the proposal is to carefully measure synonymous, and replacement polymorphisms in four well characterized regions of the genome in both melanogaster and simulans. These regions each have many genes that have already been sequenced, and they have been characterized for recombination rates in both species. Dr. Begun expects that the data from D. simulans in particular will reveal with sufficient confidence the relative levels of X and autosome variation. Under the background selection model, if deleterious mutations are partially recessive (as is probably true) then the magnitude of the effect of background selection should be greater for autosomes than for X-linked genes. Gene copies with linked recessive deleterious mutations cannot ultimately get into high frequency on either the X or an autosome, but they can drift higher in frequency on autosomes to the extent that they are sheltered by recessivity. Under hitchhiking of favorable mutations, the degree of difference expected between X-linked and autosomal genes depends on the dominance of the mutations: if they are recessive then they are more likely to fix if they are X-linked; if they are additive then the X and autosomes should experience the same rate of fixation (and thus of hitchhiking); and if they are dominant, then the autosomes should experience a larger effect. Another major question is how does the ratio of replacement to silent variation differ between the species as a function of recombination. A critical observation in this regard is that D. simulans appears to be segregating a fairly large excess of synonymous site (i.e. within protein coding regions but not affecting amino acid sequence) variation, relative to replacement (i.e. changing amino acid) variation, on the autosomes. D. simulans has slightly more variation of both categories as does D. melanogaster on the X chromosome (the ratio is the same in both species). But on the autosomes, D. simulans has proportionately much more synonymous variation, either given melanogaster levels or given autosomal replacement levels in D. simulans. Given this observation, Dr. Begun expects D. simulans to have a higher ratio or replacements to synonymous in regions of low recombination than it does regions of high recombination. Dr. Begun hopes to sequence approximately 100 loci (about 1000 bp each) in 14 lines from each species (in each, 7 from African and 7 out of Africa). These data will also reveal a wealth of information on variation among loci for different kinds of polymorphisms, as well as the way this variation corresponds to divergence between the taxa.