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The evolutionary genomics of X chromosomes

X染色体的进化基因组学

基本信息

批准号：
BB/G003076/1
负责人：
Brian Charlesworth
金额：
$ 43.03万
依托单位：
University of Edinburgh
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FG003076%2F1
关键词：
evolutionary genomics chromosomes

项目摘要

The sex of an individual is often determined by a pair of specialized chromosomes (the giant DNA molecules that carry the genetic information). These are known as the X and Y chromosomes. In animals like mammals and the fruitfly Drosophila, females carry two copies of the X, and males carry an X and a Y. Both males and females carry two copies of each of the other chromosomes, one derived from the mother and the other from the father. The X is a fairly typical chromosome but the Y has only a small number of functional genes (the portions of the DNA that specify the structures of proteins). This means that most new mutations that occur on the X and alter gene function will affect males, since there is no normal copy to cover up their effects. In contrast, a mutation on the X in a female will be present together with a normal copy, just like a mutation on another chromosome. Natural selection is better at removing harmful mutations if they arise on the X, since part of the time they are carried in males and fully express their effects. Similarly, useful mutations that increase the fitness of their carriers may have a better chance of causing evolutionary change if they arise on the X. These differences in rates of evolution between the X and the rest of the genome can have important consequences, such as a greater tendency for genes controlling species differences to be found on the X chromosome. The ability to determine the sequences of the four 'letters' in DNA that make up the genetic information means that we can directly measure rates of evolutionary change by comparing DNA sequences between species. Such comparisons have been used to ask whether rates of evolution differ between genes on the X chromosome and elsewhere in the genome. The results so far have been conflicting. We plan to use two unusually favourable systems for further comparisons of this kind, which should help to resolve these conflicts. One is a group of Drosophila species (the pseudoobscura lineage), where a regular chromosome has effectively been turned into an additional X chromosome. This allows us to compare rates of evolution of genes on this chromosome with rates for the same genes on the equivalent chromosome in other Drosophila species, where it behaves normally. We will target unusually fast-evolving genes, since these are most likely to be the ones accumulating useful mutations by natural selection. We will also collect data on variation on these genes within one of the species, Drosophila pseudoobscura. This allows the use of statistical tests for evolution by selection for useful mutations, as opposed to the chance accumulation of mutations with little effect on fitness. The other system is in the mouse, which has new (duplicate) copies of many genes, some on the X and some on regular chromosomes. This allows comparisons of the rates of evolutionary divergences among pairs of duplicates between the X chromosome and the rest of the genome. We will use the publicly available genome sequences of the mouse and its relative the rat, and ask whether duplicates on the X have higher rates of DNA sequence evolution than those elsewhere. In addition, we will study a different type of process, the addition and deletion of small pieces of DNA. This process is important for the evolution of genome size, but is poorly understood. It seems to have different properties for the X compared with the rest of the genome, with the X showing a stronger pattern of insertions being favoured by natural selection over deletions. We will use publicly available data on between species comparisons and within species variability to examine the nature of the evolutionary forces acting on additions and deletions. The research integrates evolutionary genetic and computational approaches to maximize the understanding gained from genome sequences, and will provide new tools and insights concerning evolutionary mechanisms to the research community in the UK.

一个人的性别通常是由一对特殊的染色体（携带遗传信息的巨大DNA分子）决定的。这些染色体被称为X和Y染色体。在哺乳动物和果蝇等动物中，雌性携带两个X基因，雄性携带一个X和一个Y。男性和女性都携带着其他染色体的两个副本，一个来自母亲，另一个来自父亲。X是一个相当典型的染色体，但Y只有少量的功能基因（DNA中指定蛋白质结构的部分）。这意味着大多数发生在X染色体上并改变基因功能的新突变将影响男性，因为没有正常的拷贝来掩盖它们的影响。相反，女性X染色体上的突变将与正常拷贝一起存在，就像另一条染色体上的突变一样。如果有害的突变出现在X染色体上，自然选择更善于消除它们，因为它们在一部分时间里是在男性身上携带的，并充分表达它们的影响。类似地，增加其携带者适应性的有用突变如果出现在X染色体上，则可能有更好的机会引起进化变化。X染色体和基因组其他部分之间的进化速度差异可能会产生重要的后果，例如在X染色体上发现控制物种差异的基因的趋势更大。确定DNA中构成遗传信息的四个“字母”序列的能力意味着我们可以通过比较物种之间的DNA序列来直接测量进化变化的速度。这样的比较被用来询问X染色体上的基因和基因组中其他地方的基因之间的进化速度是否不同。到目前为止，结果是相互矛盾的。我们计划使用两个非常有利的系统进行进一步的比较，这应该有助于解决这些冲突。一种是果蝇属的一组物种（拟暗果蝇谱系），其中一条规则染色体有效地变成了一条额外的X染色体。这使我们能够比较这条染色体上基因的进化速率与其他果蝇物种中相同染色体上相同基因的进化速率，在其他果蝇物种中，它的行为正常。我们将瞄准异常快速进化的基因，因为这些基因最有可能通过自然选择积累有用的突变。我们还将收集这些基因在其中一个物种Drosophila pseudosobscura内的变异数据。这允许通过选择有用的突变来使用统计测试进行进化，而不是对适应性影响很小的突变的机会积累。另一个系统是在小鼠中，它有许多基因的新（重复）拷贝，一些在X染色体上，一些在常规染色体上。这就允许比较X染色体和基因组其余部分之间的重复对之间的进化分歧率。我们将使用公开可用的小鼠及其亲属大鼠的基因组序列，并询问X上的重复是否比其他地方的DNA序列进化速率更高。此外，我们将研究一种不同类型的过程，即添加和删除小片段DNA。这一过程对于基因组大小的进化很重要，但人们对此知之甚少。与基因组的其他部分相比，X似乎具有不同的特性，X显示出更强的插入模式，这是自然选择优于缺失的结果。我们将使用公开的物种之间的比较和物种内的变异性的数据来研究的性质的进化力量作用于添加和删除。该研究整合了进化遗传学和计算方法，以最大限度地提高对基因组序列的理解，并将为英国研究界提供有关进化机制的新工具和见解。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Faster-X effects in two Drosophila lineages.

DOI：
10.1093/gbe/evu229
发表时间：
2014-10-15
期刊：
Genome biology and evolution
影响因子：
3.3
作者：
Avila V;Marion de Procé S;Campos JL;Borthwick H;Charlesworth B;Betancourt AJ
通讯作者：
Betancourt AJ

Evolution: the First Four Billion Years

进化：前四十亿年