Defining the functional landscapes of metazoan genomes
Lead Research Organisation:
MRC Harwell Institute
Department Name: Functional Genomics Unit
Abstract
'Why are some genomes really big and others quite compact?', 'What is all that 'junk' doing in our genomes?', and 'How do limbs, fins, and faces develop and evolve?' These are 3 of the 125 Big Questions in Science, identified by Science magazine on 1 July 2005. To answer these, and other questions, requires a letter-by-letter comparison of genomes -- the books-of-life -- from very different animals. Seeing whether each letter is conserved, or else replaced, does not however tell the full story, since we also need to consider whether letters are added or deleted. Taken together, the conservation, or the insertion or deletion, of letters can highlight those parts of the books-of-life that underlie the basic biology of all animals, and others that specify the differences between species. A fourth Big Question, named by Science, is 'How much will new technologies lower the cost of [genome] sequencing?' This is beginning to be answered: sequencing will soon become so cheap that many, if not all, of the animals of interest to biologists will have their genomes sequenced by 2010. Our group has already served an apprenticeship analysing the genomes of humans, mice, rats, dogs, and chickens, with an over-arching aim of pinpointing the letters of the human genome that contribute to human health. We now wish to consider all available genomes from across the animal kingdom in order to address the Big Questions in Science. In this project, we shall find genes that encode protein, and others that do not, in each of these genomes. We then will calculate the relative contributions of protein-coding genes and non-protein-coding genes in specifying (a) the ancient biology of animals, and (b) the biology that distinguishes branches of the animal evolutionary tree. As we cannot answer all other interesting questions, we will provide comprehensive information on the internet to allow other biologists from around the world to benefit from them.
Technical Summary
The three central issues addressed by this project are: 1. How does the total amount of functional DNA sequence vary, among various metazoan lineages, specifically arthropods, nematodes, tunicates, fish, birds and mammals, and does this variation reflect our understanding of organismal complexity? 2. Are the proportions of functional coding and non-coding sequence uniform across the metazoa, or, again does their ratio help to explain organismal complexity? 3. More pragmatically, how can we put together toolkits and data sets that will be of benefit to researchers working on species from across the metazoan clade? To answer these questions we will apply our published methods to identify, within diverse genome sequences, coding as well as non-coding sequence. These published methods are: the application of the neutral indel model (Lunter et al., PLoS Comput. Biol. 2: e5) to pinpoint sequence under purifying selection with respect to indels; prediction of protein-coding genes using transcripts from related species as templates (Heger et al., Genome Research, in press); prediction of orthology and paralogy using PhyOP (PLoS Comput. Biol. 2: e133); and, the inference of purifying selection within non-coding sequence (Ponjavic et al., Genome Res. 2007 Mar 26; [Epub ahead of print]). Although these methods could be applied immediately, we will also extend their predictive power by improving alignment quality, by clustering functional elements, and by developing Bayesian models that consider substitutions and indels jointly. Evaluations of the balance of coding versus non-coding functional sequence for very divergent genomes should improve our understanding of organismal complexity. Our studies will also shed light on lineage-specific biology of animal species that are important in agriculture and aquaculture. Our predictions of orthology and paralogy between closely-related, as well as divergent, species will be made freely available on the internet.
Organisations
Publications
Alföldi J
(2011)
The genome of the green anole lizard and a comparative analysis with birds and mammals.
in Nature
Chodroff RA
(2010)
Long noncoding RNA genes: conservation of sequence and brain expression among diverse amniotes.
in Genome biology
Kong L
(2010)
Accelerated evolution of PAK3- and PIM1-like kinase gene families in the zebra finch, Taeniopygia guttata.
in Molecular biology and evolution
Li Y
(2013)
Rapid Evolution of Beta-Keratin Genes Contribute to Phenotypic Differences That Distinguish Turtles and Birds from Other Reptiles
in Genome Biology and Evolution
Meader S
(2010)
Massive turnover of functional sequence in human and other mammalian genomes.
in Genome research
Ponting CP
(2010)
Transcribed dark matter: meaning or myth?
in Human molecular genetics
Ponting CP
(2011)
Rapid turnover of functional sequence in human and other genomes.
in Annual review of genomics and human genetics
Rands CM
(2013)
Insights into the evolution of Darwin's finches from comparative analysis of the Geospiza magnirostris genome sequence.
in BMC genomics
Sanchez-Pulido L
(2012)
A common ancestry for BAP1 and Uch37 regulators
in Bioinformatics
Shaffer HB
(2013)
The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage.
in Genome biology
Description | A better understanding of the regions of the human genome that are functional, as opposed to the great majority of sequence that is functionally inert. |
Exploitation Route | Disease variants will fall only in functional regions of the genome. Therefore, this work helps to determine which mutations contribute to human disease, and which do not. |
Sectors | Education,Healthcare |
Description | Our work has contributed substantially to the new view of the human genome as being a 'wilderness', with most of the genome being nonfunctional interspersed with small regions of functional DNA. |
First Year Of Impact | 2011 |
Sector | Education |
Impact Types | Societal |
Description | Ponting - Advice re Scottish Highers Qualifications |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | BBC Radio 4 interview (2010) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | C.P. interviewed by Richard Dawkins as part of the series "The Age of the Genome" broadcast on BBC Radio 4, 9pm. Davies and Ponting interviews with Richard Dawkins as part of the series "The Age of the Genome" broadcast on no actual impacts realised to date |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.bbc.co.uk/programmes/p008r4l4 |
Description | BBC Radio 4 interview (December 2012) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | C.P interviewed about ENCODE on Radio 4 Frontiers science programme. http://www.bbc.co.uk/programmes/b01p424w http://www.bbc.co.uk/programmes/b01p424w no actual impacts realised to date |
Year(s) Of Engagement Activity | 2012 |
URL | http://www.bbc.co.uk/programmes/b01p424w |
Description | BBC World Service Broadcast (Aug 2011) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | C.P. took part in BBC World Service programme: 'The Forum' discussing "In genetics, what is the nature of the biological barriers that keep species separate?" no actual impacts realised to date |
Year(s) Of Engagement Activity | 2011 |
URL | http://www.bbc.co.uk/programmes/p00jcgmx |
Description | Feature in University of Oxford staff magazine |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Postgraduate students |
Results and Impact | Ponting group work on the zebra finch genome was featured in Blueprint, the Staff magazine for the University of Oxford. Feature on work on the zebra finch genome in Blueprint, the Staff magazine for the University of Oxford. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2010 |
Description | Nature news article (Sep 2012) |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | C.P. quoted in news article in Nature on 'ENCODE: The human encyclopaedia' Nature489,46-48(06 September 2012), http://www.nature.com/news/encode-the-human-encyclopaedia-1.11312 no actual impacts realised to date |
Year(s) Of Engagement Activity | 2012 |
URL | http://www.nature.com/news/encode-the-human-encyclopaedia-1.11312 |
Description | Oxford Science Blog - Human Genome 10th anniversary |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | C.P. contributed to an Oxford Science Blog in the run up to the tenth anniversary of the announcement of the Human Genome Draft sequence. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.ox.ac.uk/media/science_blog/100326.html. |
Description | Radio interview - Australian Broadcasting Corporation |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Professor C.P. was interviewed by Robyn Williams for ABC's The Science Show. http://www.abc.net.au/radionational/programs/scienceshow/genome-research---achievements-and-hopes/3073444 Chris Ponting was interviewed by Robyn Williams for ABC's The Science Show. no actual impacts realised to date |
Year(s) Of Engagement Activity | 2010 |
URL | http://www.abc.net.au/radionational/programs/scienceshow/genome-research---achievements-and-hopes/30... |
Description | Represented Unit at MRC Centenary Mini Science Festival, Oxford, June 2013 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | Yes |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Helped to man the Unit stall/exhibits and talk to public at the MRC Centenary Mini Science Festival in Bonn Square, Oxford, 22 June 2013 Greater local public awareness of research work undertaken by the Unit and MRC |
Year(s) Of Engagement Activity | 2013 |
Description | Wall Street Journal article |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | C.P. quoted re ENCODE in article in The Wall Street Journal on''Junk DNA' Debunked' http://online.wsj.com/article/SB10000872396390443589304577633560336453228.html no actual impacts realised to date |
Year(s) Of Engagement Activity | 2012 |
URL | http://online.wsj.com/article/SB10000872396390443589304577633560336453228.html |