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Inference of Evolutionary Histories of Mobile DNAs

Reference	BB/H009884/1
Principal Investigator / Supervisor	Professor John Brookfield
Co-Investigators / Co-Supervisors
Institution	University of Nottingham
Department	Sch of Biology
Funding type	Research
Value (£)	303,933
Status	Completed
Type	Research Grant
Start date	01/08/2010
End date	31/07/2013
Duration	36 months

Abstract

Transposable elements (TEs) form a population of replicating lineages which are found in chromosomes, and the elements of a given family have homologous DNA sequences due to their shared descent. The variation in the sequences can be used to infer what their evolutionary histories have been, in the light of models of their proliferation through chromosomes. However, it is still not clear how the modelling of these sequences should be carried out. The coalescent methods that dominate inference in population genetics assume that only a small sample of the population of lineages are sampled, which will not always be true for TEs given the complete genomic information that is available. Branching process methods, which are used to look at, for example, variations in speciation rates, are less effective when sampling is incomplete, and sampling can never be complete, in that element insertion sites can be created, can be the donors for further transposition events, and can then be lost. The project will create hybrid, although computationally demanding, methods to carry out assessment of evolutionary processes, using Markov Chain Monte Carlo (MCMC) methods. Selection and horizontal transfer of elements will be incorporated in these models of inference and the evidence supplied for selection for transposable element function found in some data sets will be quantified. While methods to be developed are inspired primarily by mammalian TE families, the software to be generated will allow workers interested in TEs from any group to create evolutionary inferences from current sequence data.

Summary

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 thebasis 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.

Impact Summary

The work will create scientific papers and computer software which will allow researchers to investigate the evolutionary history of families of mobile DNAs, using, as the basis of these interpretations, the DNA sequences that are being derived in increasing numbers from genome projects on various species and individuals. In addition to scientific publications, the PI and the PDRA will also make presentations at scientific meetings. Interpretation of genomic information is a burgeoning field with applications in agriculture and human and animal health. In the case of investigations, as here, of the mobile, interspersed repetitive, component of genomes, another possible spin-off will be that a greater understanding of the evolutionary dynamics of these sequences will form an important input into attempts to genetically modify wild populations of insect vectors. These might either of vectors of human disease, or, potentially, vectors of plant or animal pathogens, such as blue-tongue. The PI will continue his ongoing work on outreach to young people and through media interactions to promote the public understanding of science, a task that is of particular importance for researchers in evolutionary biology. Another important impact of the work will come from the training of the post-doctoral researcher in skills in quantitative population and evolutionary genetics and their application to genomic problems, which the PI can supply.

Committee	Research Committee A (Animal disease, health and welfare)
Research Topics	Technology and Methods Development
Research Priority	Technology Development for the Biosciences
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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