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  Bioinformatic studies of mobile DNAs in vertebrates


   School of Life Sciences

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  Prof J F Y Brookfield, Prof O Hanotte  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

44% of the human genome, and similar proportions in other vertebrate species, consists of mobile DNAs or their inactive descendants. These “transposable elements” are scattered throughout genomes as a result of their past or present mobility, and many have been characterised as “junk DNA”. They form distinct classes: the Class I elements, or retrotransposons, move via an RNA intermediate, while Class II elements move to new chromosomal locations as DNA entities. Transposable elements are capable of spreading through genomes by replication in transposition, and their copy numbers can increase to hundreds of thousands or millions, even if they convey no benefits to their hosts. They are indeed frequently regarded as parasitic DNAs. Through bioinformatic comparisons between the genomes of mammal groups, it is possible to trace the life cycle of these genomic parasites, as they proliferate through their hosts’ genomes, and then become inactive, living on in the genomes and decaying in sequence. Studies of the DNA sequences of orthologous and paralogous transposable element copies allow identification of horizontal transfer events, against a general pattern of vertical inheritance. Genomic information has now expanded from encompassing a single genome per species, to knowledge of population genomics, where genomic sites of transposable elements can be characterised by their population frequencies, which reveal much about whether individual transposable element insertions are harmful, advantageous or neutral in their effects on host fitness.

The possibility that some elements have advantageous effects creates a different way of regarding mobile DNAs, as ancestrally parasitic DNAs that may have subsequently evolved functions that are adaptive for the host. There exist powerful statistical tests, examining sequence conservation, which can identify whether a now-inactive copy of a previously mobile sequence family is now conferring any adaptive benefit to its host. The project will consist of applying bioinformatics analyses to whole genome information from wild and domesticated species of vertebrates, including variation within- and between-species, to establish whether interspersed repetitive sequences make a major contribution to adaptive change. The candidate should have some experience and expertise with bioinformatics tools, an aptitude for statistical and quantitative reasoning, and a strong grasp of principle of evolutionary biology and population genetics as applied to DNA sequences.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.

Funding Notes

Home applicants should contact the supervisor to determine the current funding status for this project. EU applicants should visit the Graduate School webpages for information on specific EU scholarships http://www.nottingham.ac.uk/graduateschool/funding/prospective-students/index.aspx. International applicants should visit our International Research Scholarships page for information regarding fees and funding at the University http://www.nottingham.ac.uk/studywithus/international-applicants/scholarships-fees-and-finance/index.aspx.

References

Hellen, Elizabeth H.B. and Brookfield, John F.Y. (2012) The diversity of Class II transposable elements in mammalian genomes has arisen from ancestral phylogenetic splits during ancient waves of proliferation through the genome. Mol. Biol. Evol. 30(1):100–108 doi:10.1093/molbev/mss206

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