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Inference of Evolutionary Histories of Mobile DNAs

移动DNA进化史的推断

基本信息

批准号：
BB/H009884/1
负责人：
John Brookfield
金额：
$ 38.73万
依托单位：
University of Nottingham
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%2FH009884%2F1
关键词：
Inference Evolutionary Histories Mobile DNAs

项目摘要

One of the major discoveries that has been made in the study of the genomes of higher organisms is that only a small fraction of the DNA in the chromosomes consists of genes, and an even smaller fraction of the DNA is involved in specifying the amino acid sequences of proteins. In organisms with large genomes, such as man, it remains true that the majority of the DNA is of unknown function. Of this unexplained DNA, a large fraction (around 40% of the genome in total) consists of repeated DNAs that have become scattered throughout the chromosomes as a result of their capacity to 'transpose'- to move to new chromosomal locations. These transposable elements, or TEs, replicate as they move to new locations, and so, over time, their numbers in the chromosomes will tend to build up. For this reason, they are now usually viewed as primarily selfish DNAs, increasing their abundance in the chromosomes in which they 'live', but only rarely conferring any advantage on the organism in which they are found. The capacity to move between chromosomal locations has the effect that copies of these TEs, found at different sites, share common ancestry, which could have consisted of a common ancestor just one fruit fly's generation ago, or could have been a common ancestor fifty million years ago, in the case of mammalian TEs. The evolutionary relationships between these sequences tell us about the process through which they have come to spread themselves through the chromosomes, either in the past, or in an ongoing process. The science of population genetics interprets data on DNA sequence variation that we see today, and uses this to reconstruct evolutionary events in the past. This can be used to interpret the variation in TE families, and has been used in this way by the Principal Investigator. This project will allow inferences of the evolutionary histories of families of elements to be made in a more formal way, assessing the probabilities of various evolutionary scenarios on the basis of the transposable element sequence data that we now see. However, the situation is complex, and many different mathematical approaches can be used in this process of inference. This project will produce more sophisticated methods, which will combine features of earlier models, and will allow us to say, from a collection of DNA sequences, how likely are various differing histories of these sequences. As these mobile DNAs, the TEs, constitute more than forty per cent of our DNA, and as they are often being put to use in the creation of new adaptive functions, a full understanding of eukaryotic evolution, and human health, requires us to be able to see where these elements are derived from, and what, if any, purposes they now serve in our genomes. The project will allow the sophisticated mathematical approaches to be developed to be accessed using user-friendly software, such that workers worldwide who have discovered new TE families in any genome will be able to draw inferences about the families' evolutionary histories.

研究高等生物基因组的一个重大发现是，染色体中只有一小部分DNA是由基因组成的，而参与确定蛋白质氨基酸序列的DNA就更少了。在具有大基因组的生物体中，例如人类，大多数DNA的功能仍然未知。在这些无法解释的DNA中，有很大一部分（约占基因组总数的40%）是由重复的DNA组成的，这些DNA由于它们能够“转座”-移动到新的染色体位置-而分散在整个染色体上。这些转座因子或TE在移动到新的位置时进行复制，因此，随着时间的推移，它们在染色体中的数量往往会增加。由于这个原因，它们现在通常被视为主要是自私的DNA，增加了它们“生活”的染色体中的丰度，但很少赋予它们被发现的生物体任何优势。在染色体位置之间移动的能力具有这样的效果，即在不同位点发现的这些TE的副本具有共同的祖先，它们可能是同一个果蝇世代前的共同祖先，也可能是五千万年前的共同祖先，就哺乳动物的TE而言。这些序列之间的进化关系告诉我们它们通过染色体传播的过程，无论是在过去还是在一个持续的过程中。群体遗传学解释我们今天看到的DNA序列变异数据，并利用这些数据来重建过去的进化事件。这可用于解释TE家族的变异，主要研究者已以此方式使用。该项目将允许以更正式的方式推断元素家族的进化历史，根据我们现在看到的转座因子序列数据评估各种进化情景的概率。然而，情况是复杂的，在这个推理过程中可以使用许多不同的数学方法。这个项目将产生更复杂的方法，它将结合早期模型的联合收割机特征，并使我们能够从DNA序列的集合中判断这些序列的各种不同历史的可能性。由于这些移动的DNA，即TE，构成了我们DNA的40%以上，而且由于它们经常被用于创造新的适应功能，因此要全面了解真核生物的进化和人类健康，就需要我们能够看到这些元素来自何处，以及它们现在在我们的基因组中起着什么作用（如果有的话）。该项目将允许开发复杂的数学方法，使用用户友好的软件进行访问，这样，在任何基因组中发现新TE家族的世界各地的工作人员将能够推断家族的进化历史。