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EvoGenMed SIGNED

Evolutionary genomics: new perspectives and novel medical applications

Total Cost €

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EC-Contrib. €

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Partnership

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Project "EvoGenMed" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF BATH 

Organization address
address: CLAVERTON DOWN
city: BATH
postcode: BA2 7AY
website: http://www.bath.ac.uk/

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 2˙497˙996 €
 EC max contribution 2˙497˙996 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-ADG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF BATH UK (BATH) coordinator 2˙260˙496.00
2    THE UNIVERSITY OF EDINBURGH UK (EDINBURGH) participant 137˙500.00
3    MAX DELBRUECK CENTRUM FUER MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT (MDC) DE (BERLIN) participant 100˙000.00

Map

 Project objective

To make for better diagnostics and safer applications of genomics we need a better understanding of our genome and how it functions. Until recently we thought we knew: intergenic sequence must be largely “junk” and mutations that, for example, affect genes but not the protein (synonymous mutations) must be effectively neutral. This degenerate genome view accords with the nearly-neutral theory’s prediction that selection will be weaker when populations are small. But is this all there is to it? I shall investigate two new interrelated perspectives on genome evolution. First, I suggest that to mitigate errors, owing to our high error rates, our genome can be under stronger, not weaker, selection. Second, that errors might be a source of evolutionary novelty. Error mitigation, my team has shown, often involves selection on seemingly innocuous mutations such as synonymous changes. Remarkably, we discovered that selection to ensure error-proof splicing is possibly more prevalent on synonymous mutations when populations are small, making seemingly innocuous mutations stronger candidates for human diseases. I shall provide the first test of the new error-proofing perspective through comparative genomic analysis on synonymous site evolution. To investigate error as a source of novelty I shall consider whether expression piggy-backing (expression of a gene affecting its neighbors) forces rewiring of gene networks. Importantly, I shall translate our new understanding to enable better diagnostics and improved therapeutics. I shall develop a much-needed computer package to identify candidate disease-causing synonymous changes. In addition, knowing how synonymous sites modulate splicing will allow me to design better intronless transgenes. Transgenes must also be inserted in genomic regions immune to piggy-backing. I will examine transposable element related piggy-backing to characterize “safe” sites for therapeutic gene insertion and mammalian transgenesis more generally.

 Publications

year authors and title journal last update
List of publications.
2020 Christine Mordstein, Rosina Savisaar, Robert S. Young, Jeanne Bazile, Lana Talmane, Juliet Luft, Michael Liss, Martin S. Taylor, Laurence D. Hurst, Grzegorz Kudla
Codon Usage and Splicing Jointly Influence mRNA Localization
published pages: , ISSN: 2405-4712, DOI: 10.1016/j.cels.2020.03.001
Cell Systems 2020-04-15
2019 Alexander T. Ho, Laurence D. Hurst
In eubacteria, unlike eukaryotes, there is no evidence for selection favouring fail-safe 3’ additional stop codons
published pages: e1008386, ISSN: 1553-7404, DOI: 10.1371/journal.pgen.1008386
PLOS Genetics 15/9 2020-01-29
2017 Haoxuan Liu, Yanxiao Jia, Xiaoguang Sun, Dacheng Tian, Laurence D. Hurst, Sihai Yang
Direct Determination of the Mutation Rate in the Bumblebee Reveals Evidence for Weak Recombination-Associated Mutation and an Approximate Rate Constancy in Insects
published pages: 119-130, ISSN: 0737-4038, DOI: 10.1093/molbev/msw226
Molecular Biology and Evolution 34/1 2020-01-29
2016 Jichang Wang, Manvendra Singh, Chuanbo Sun, Daniel Besser, Alessandro Prigione, Zoltán Ivics, Laurence D Hurst, Zsuzsanna Izsvák
Isolation and cultivation of naive-like human pluripotent stem cells based on HERVH expression
published pages: 327-346, ISSN: 1754-2189, DOI: 10.1038/nprot.2016.016
Nature Protocols 11/2 2020-01-29
2017 Rosina Savisaar, Laurence D. Hurst
Estimating the prevalence of functional exonic splice regulatory information
published pages: , ISSN: 0340-6717, DOI: 10.1007/s00439-017-1798-3
Human Genetics 2020-01-29
2016 Aoife McLysaght, Laurence D. Hurst
Open questions in the study of de novo genes: what, how and why
published pages: 567-578, ISSN: 1471-0056, DOI: 10.1038/nrg.2016.78
Nature Reviews Genetics 17/9 2020-01-29
2016 XianMing Wu, Laurence D. Hurst
Determinants of the Usage of Splice-Associated cis -Motifs Predict the Distribution of Human Pathogenic SNPs
published pages: 518-529, ISSN: 0737-4038, DOI: 10.1093/molbev/msv251
Molecular Biology and Evolution 33/2 2020-01-29
2016 Zhengqing Xie, Long Wang, Lirong Wang, Zhiqiang Wang, Zhenhua Lu, Dacheng Tian, Sihai Yang, Laurence D. Hurst
Mutation rate analysis via parent–progeny sequencing of the perennial peach. I. A low rate in woody perennials and a higher mutagenicity in hybrids
published pages: 20161016, ISSN: 0962-8452, DOI: 10.1098/rspb.2016.1016
Proceedings of the Royal Society B: Biological Sciences 283/1841 2020-01-29
2016 Long Wang, Yanchun Zhang, Chao Qin, Dacheng Tian, Sihai Yang, Laurence D. Hurst
Mutation rate analysis via parent–progeny sequencing of the perennial peach. II. No evidence for recombination-associated mutation
published pages: 20161785, ISSN: 0962-8452, DOI: 10.1098/rspb.2016.1785
Proceedings of the Royal Society B: Biological Sciences 283/1841 2020-01-29
2018 Stefanie Mühlhausen, Hans Dieter Schmitt, Kuan-Ting Pan, Uwe Plessmann, Henning Urlaub, Laurence D. Hurst, Martin Kollmar
Endogenous Stochastic Decoding of the CUG Codon by Competing Ser- and Leu-tRNAs in Ascoidea asiatica
published pages: 2046-2057.e5, ISSN: 0960-9822, DOI: 10.1016/j.cub.2018.04.085
Current Biology 28/13 2020-01-29
2017 Áine N O’Toole, Laurence D Hurst, Aoife McLysaght
Faster Evolving Primate Genes Are More Likely to Duplicate
published pages: 107-118, ISSN: 0737-4038, DOI: 10.1093/molbev/msx270
Molecular Biology and Evolution 35/1 2020-01-29
2018 Rosina Savisaar, Laurence D. Hurst
Exonic splice regulation imposes strong selection at synonymous sites
published pages: , ISSN: 1088-9051, DOI: 10.1101/gr.233999.117
Genome Research 2020-01-29
2017 Gabriele Thumann, Nina Harmening, Cécile Prat-Souteyrand, Corinne Marie, Marie Pastor, Attila Sebe, Csaba Miskey, Laurence D. Hurst, Sabine Diarra, Martina Kropp, Peter Walter, Daniel Scherman, Zoltán Ivics, Zsuzsanna Izsvák, Sandra Johnen
Engineering of PEDF-Expressing Primary Pigment Epithelial Cells by the SB Transposon System Delivered by pFAR4 Plasmids
published pages: 302-314, ISSN: 2162-2531, DOI: 10.1016/j.omtn.2017.02.002
Molecular Therapy - Nucleic Acids 6 2020-01-29
2017 Liam Abrahams, Laurence D Hurst
Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts
published pages: 3064-3080, ISSN: 0737-4038, DOI: 10.1093/molbev/msx223
Molecular Biology and Evolution 34/12 2020-01-29
2016 Rosina Savisaar, Laurence D. Hurst
Purifying Selection on Exonic Splice Enhancers in Intronless Genes
published pages: 1396-1418, ISSN: 0737-4038, DOI: 10.1093/molbev/msw018
Molecular Biology and Evolution 33/6 2020-01-29
2018 Liam Abrahams, Laurence D Hurst
Refining the ambush hypothesis: evidence that GC and AT rich bacteria employ different frameshift defence strategies
published pages: , ISSN: 1759-6653, DOI: 10.1093/gbe/evy075
Genome Biology and Evolution 2020-01-29
2018 Haoxuan Liu, Ju Huang, Xiaoguang Sun, Jing Li, Yingwen Hu, Luyao Yu, Gianni Liti, Dacheng Tian, Laurence D. Hurst, Sihai Yang
Tetrad analysis in plants and fungi finds large differences in gene conversion rates but no GC bias
published pages: 164-173, ISSN: 2397-334X, DOI: 10.1038/s41559-017-0372-7
Nature Ecology & Evolution 2/1 2020-01-29
2015 Laurence D. Hurst, Avazeh T. Ghanbarian, Alistair R. R. Forrest, Lukasz Huminiecki
The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome
published pages: e1002315, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.1002315
PLOS Biology 13/12 2020-01-29
2018 Ju Huang, Jing Li, Jun Zhou, Long Wang, Sihai Yang, Laurence D. Hurst, Wen-Hsiung Li, Dacheng Tian
Identifying a large number of high-yield genes in rice by pedigree analysis, whole-genome sequencing, and CRISPR-Cas9 gene knockout
published pages: 201806110, ISSN: 0027-8424, DOI: 10.1073/pnas.1806110115
Proceedings of the National Academy of Sciences 2020-01-29
2017 Julianna Zadora, Manvendra Singh, Florian Herse, Lukasz Przybyl, Nadine Haase, Michaela Golic, Hong Wa Yung, Berthold Huppertz, Judith E. Cartwright, Guy Whitley, Guro M. Johnsen, Giovanni Levi, Annette Isbruch, Herbert Schulz, Friedrich C. Luft, Dominik N. Müller, Anne Cathrine Staff, Laurence D. Hurst, Ralf Dechend, Zsuzsanna Izsvák
Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker
published pages: 1824-1839, ISSN: 0009-7322, DOI: 10.1161/circulationaha.117.028110
Circulation 136/19 2020-01-29
2017 Ruth T. Casey, David B. Ascher, Eleanor Rattenberry, Louise Izatt, Katrina A. Andrews, Helen L. Simpson, Benjamen Challis, Soo-Mi Park, Venkata R. Bulusu, Fiona Lalloo, Douglas E. V. Pires, Hannah West, Graeme R. Clark, Philip S. Smith, James Whitworth, Thomas G. Papathomas, Phillipe Taniere, Rosina Savisaar, Laurence D. Hurst, Emma R. Woodward, Eamonn R. Maher
SDHA related tumorigenesis: a new case series and literature review for variant interpretation and pathogenicity
published pages: 237-250, ISSN: 2324-9269, DOI: 10.1002/mgg3.279
Molecular Genetics & Genomic Medicine 5/3 2020-01-29
2017 Laurence D. Hurst, Nizar N. Batada
Depletion of somatic mutations in splicing-associated sequences in cancer genomes
published pages: , ISSN: 1474-760X, DOI: 10.1186/s13059-017-1337-5
Genome Biology 18/1 2020-01-29
2017 Savisaar Rosina, Laurence D. Hurst
Both maintenance and avoidance of RNA-binding protein interactions constrain coding sequence evolution
published pages: msx061, ISSN: 0737-4038, DOI: 10.1093/molbev/msx061
Molecular Biology and Evolution 34 2020-01-29
2019 Long Wang, Yilun Ji, Yingwen Hu, Huaying Hu, Xianqin Jia, Mengmeng Jiang, Xiaohui Zhang, Lina Zhao, Yanchun Zhang, Yanxiao Jia, Chao Qin, Luyao Yu, Ju Huang, Sihai Yang, Laurence D. Hurst, Dacheng Tian
The architecture of intra-organism mutation rate variation in plants
published pages: e3000191, ISSN: 1545-7885, DOI: 10.1371/journal.pbio.3000191
PLOS Biology 17/4 2020-01-29

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