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Molecular evolution and variation in genomic regions with low recombination

低重组基因组区域的分子进化和变异

基本信息

批准号：
BB/H006028/1
负责人：
Brian Charlesworth
金额：
$ 45.21万
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：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FH006028%2F1
关键词：
Molecular evolution variation genomic regions

项目摘要

One of the classical problems of biology is the evolutionary role of sexual reproduction. This involves the bringing together of the genomes of two parents, and reshuffling them by the process known as genetic recombination, so that an individual offspring receives a mixture of contributions from each parent. This allows the evolutionary fates of genetic variants at different places in the genome to behave more or less independently of each other. One consequence of this is that natural selection can act at one site in the genome without interfering with what happens at other sites. Many specific models of evolutionary processes that can cause interference between different sites when sex is absent have been proposed: they all predict that selection is less effective in the absence of sex, leading to a large loss in fitness. It is, however, hard to test these predictions in nature, since asexual species or populations are very rare, and in most cases have arisen only recently from sexual ancestors. Nevertheless, it is important to test these predictions, both for the intellectual interest in understanding why sexual reproduction is so common in nature, and because there are plans to develop asexual strains of plants for the purpose of breeding crops. A way around this difficulty is to compare different regions of the same genome. Genetic recombination, the process that creates the reshuffling of parental contributions during sexual reproduction, is rare or absent in some parts of the genome, especially the part of the genome known as the heterochromatin. Such parts of the genome are expected to behave like asexual species, in terms of their evolutionary patterns. Until very recently, however, the heterochromatin has been impossible to study at the level of DNA sequences, since it contains large amounts of DNA that are repeated over and over again, making it hard to study at the sequence level. Recent breakthroughs in research on the fruitfly Drosophila, the best-studied model animal species, have led to the characterisation of several hundred genes in the heterochromatin. This means we are now in a position to study evolution and variation of genes in the heterochromatin almost as easily as genes in the rest of the genome, and can therefore see whether or not they show the patterns expected from their lack of recombination. Sophisticated statistical methods are available for this purpose, but require large datasets to be used effectively. We plan to exploit new technologies for sequencing DNA, which allow large quantities of information to be generated rapidly and cheaply. We will use these to generate data on variability in a large number of genes in the heterochromatin and in other parts of the genome, within populations of two closely related species of Drosophila. By combining the results of these studies with computer-based analyses of the published genome sequences of other species of Drosophila, we will be able to determine whether or not the patterns that we seen in regions of the genome with low levels of recombination agree with our theoretical models. If they do, we will have much more convincing evidence than currently exists that sexual reproduction has an evolutionary advantage, and that an absence of sex leads to a severe decline in fitness. The data that we generate can also be used for answering a wide range of other questions, such as the extent to which there is any recombination in the heterochromatin, the extent to which natural selection acts on DNA sequences that are not involved in determining protein sequences, and the intensity of selection acting on the protein sequences themselves. We will make these data publicly available through databases, scientific publications and conferences. Given the great public interest in questions of this kind, we will also communicate our results to the media.

生物学的一个经典问题是有性生殖的进化作用。这包括将父母双方的基因组聚集在一起，并通过称为基因重组的过程重新洗牌，这样一个单独的后代就能从父母双方那里得到混合的贡献。这使得基因组中不同位置的遗传变异的进化命运或多或少地相互独立。这样做的一个结果是，自然选择可以作用于基因组的一个位点而不干扰其他位点。当性别缺失时，许多特定的进化过程模型会导致不同位点之间的干扰。这些模型都预测，在没有性别的情况下，选择的效率会降低，从而导致适应性的大幅下降。然而，很难在自然界中验证这些预测，因为无性物种或种群非常罕见，而且在大多数情况下，直到最近才从有性祖先中出现。然而，验证这些预测是很重要的，一方面是为了理解为什么有性繁殖在自然界如此普遍，另一方面是为了培育农作物而开发无性植物品系的计划。解决这个难题的一个方法是比较同一基因组的不同区域。基因重组，即在有性生殖过程中产生亲代基因重组的过程，在基因组的某些部分很少或不存在，尤其是在被称为异染色质的基因组部分。从进化模式来看，基因组的这些部分预计会表现得像无性物种。然而，直到最近，在DNA序列水平上研究异染色质是不可能的，因为它包含大量的DNA，这些DNA是一遍又一遍重复的，因此很难在序列水平上进行研究。果蝇是研究得最好的模式动物物种，最近对果蝇的研究取得了突破，导致了异染色质中数百个基因的特征。这意味着我们现在可以像研究基因组其他部分的基因一样轻松地研究异染色质中基因的进化和变异，因此可以看到它们是否显示出缺乏重组所期望的模式。复杂的统计方法可用于此目的，但需要有效地使用大型数据集。我们计划开发新的DNA测序技术，使大量信息能够快速而廉价地生成。我们将使用这些数据来生成异染色质和基因组其他部分中大量基因的变异性数据，这些数据来自两个密切相关的果蝇物种。通过将这些研究结果与其他果蝇物种已发表的基因组序列的计算机分析相结合，我们将能够确定我们在基因组低水平重组区域所看到的模式是否与我们的理论模型一致。如果确实如此，我们将拥有比目前更有说服力的证据，证明有性繁殖具有进化优势，而性的缺失会导致适应性的严重下降。我们生成的数据也可以用于回答广泛的其他问题，例如异染色质中存在任何重组的程度，自然选择作用于不参与决定蛋白质序列的DNA序列的程度，以及作用于蛋白质序列本身的选择强度。我们将通过数据库、科学出版物和会议公开提供这些数据。鉴于公众对这类问题的极大兴趣，我们也将向媒体通报我们的结果。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The relation between recombination rate and patterns of molecular evolution and variation in Drosophila melanogaster.

DOI：
10.1093/molbev/msu056
发表时间：
2014-04
期刊：
Molecular biology and evolution
影响因子：
10.7
作者：
Campos JL;Halligan DL;Haddrill PR;Charlesworth B
通讯作者：
Charlesworth B

Molecular evolution in nonrecombining regions of the Drosophila melanogaster genome.

DOI：
10.1093/gbe/evs010
发表时间：
2012
期刊：
Genome biology and evolution
影响因子：
3.3
作者：
Campos JL;Charlesworth B;Haddrill PR
通讯作者：
Haddrill PR

Codon usage bias and effective population sizes on the X chromosome versus the autosomes in Drosophila melanogaster.

X染色体上的密码子使用偏差和有效的人口大小与果蝇果蝇中的常染色体相比。

DOI：
10.1093/molbev/mss222
发表时间：
2013-04
期刊：
Molecular biology and evolution
影响因子：
10.7
作者：
Campos JL;Zeng K;Parker DJ;Charlesworth B;Haddrill PR
通讯作者：
Haddrill PR

Variation in the Intensity of Selection on Codon Bias over Time Causes Contrasting Patterns of Base Composition Evolution in Drosophila.

密码子偏倚选择强度随时间的变化导致果蝇碱基组成进化模式的对比。

DOI：
10.1093/gbe/evw291
发表时间：
2017-01-01
期刊：
Genome biology and evolution
影响因子：
3.3
作者：
Jackson BC;Campos JL;Haddrill PR;Charlesworth B;Zeng K
通讯作者：
Zeng K

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