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Professor Aoife Mc Lysaght

Professor (Genetics)

 Gene expression level as a keystone to understanding gene duplication: evolutionary constraints, opportunities, and disease
 SFI ERC Supplement
 Dosage-sensitive genes in evolution and disease
 Origin and Evolution of Vertebrate de novo Genes
 Gene Gains, Losses and Relocations during Vertebrate Evolution

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Details Date
President, Society for Molecular Biology and Evolution (SMBE) 2018
External Advisory Board for the Milner Centre for Evolution, Bath University 2016
Senior Editor of Molecular Biology and Evolution Journal 2015
Associate Editor of Molecular Biology and Evolution 2005
Associate Editor of Genome Biology and Evolution Journal 2015
Editorial Board Member of Cell Reports 2011
Elected as Treasurer of the Society for Molecular Biology and Evolution (three year term) 2012
External Examiner, Bioinformatics and Genetics Degree, NUI Maynooth 2008
Language Skill Reading Skill Writing Skill Speaking
English Fluent Fluent Fluent
French Medium Medium Medium
Italian Basic Basic Basic
Details Date From Date To
President, Society for Molecular Biology and Evolution 2018 2020
Treasurer, Society for Molecular Biology and Evolution 2012 2014
Member - Society for Molecular Biology and Evolution (SMBE) 2005 present
Member - Genetics Society (UK) 1999 present
Vakirlis N, McLysaght A., Computational Prediction of De Novo Emerged Protein-Coding Genes., Methods in molecular biology (Clifton, N.J.), 1851, 2019, p63-81 , Journal Article, PUBLISHED  DOI
Yoichiro Nakatani and Aoife McLysaght, Macrosynteny analysis shows the absence of ancient whole-genome duplication in lepidopteran insects., Proceedings of the National Academy of Sciences (USA), 2019, Journal Article, IN_PRESS
O'Toole, Ã .N. and Hurst, L.D. and McLysaght, A., Faster Evolving Primate Genes Are More Likely to Duplicate, Molecular Biology and Evolution, 35, (1), 2018, p107-118 , Notes: [cited By 0], Journal Article, PUBLISHED  DOI
Conway E, Jerman E, Healy E, Ito S, Holoch D, Oliviero G, Deevy O, Glancy E, Fitzpatrick DJ, Mucha M, Watson A, Rice AM, Chammas P, Huang C, Bracken AP., A Family of Vertebrate-Specific Polycombs Encoded by the LCOR/LCORL Genes Balance PRC2 Subtype Activities., Molecular Cell, 70, (3), 2018, p408-421 , Journal Article, PUBLISHED  DOI
Glenfield C, McLysaght A., Pseudogenes Provide Evolutionary Evidence for the Competitive Endogenous RNA Hypothesis., Molecular biology and evolution, 35, (12), 2018, p2886-2899 , Journal Article, PUBLISHED  DOI
Rice A., McLysaght A., Dosage sensitivity is a major determinant of human copy number variant pathogenicity, Nature Communications, 8, 2017, p14366 , Journal Article, PUBLISHED  TARA - Full Text  DOI
Nakatani Y, McLysaght A, Genomes as documents of evolutionary history: A probabilistic macrosynteny model for the reconstruction of ancestral genomes, Bioinformatics, 33, (14), 2017, pi369 - i378, Journal Article, PUBLISHED  DOI  URL
Rice A.M, McLysaght A, Dosage-sensitive genes in evolution and disease, BMC Biology, 15, (1), 2017, p78-, Journal Article, PUBLISHED  TARA - Full Text  DOI  URL
McLysaght A, Hurst L.D, Open questions in the study of de novo genes: What, how and why, Nature Reviews Genetics, 17, (9), 2016, p567 - 578, Notes: [Export Date: 27 September 2016], Journal Article, PUBLISHED  DOI  URL
Xie T, Yang QY, Wang XT, McLysaght A, Zhang HY., Spatial Colocalization of Human Ohnolog Pairs Acts to Maintain Dosage-Balance., Molecular biology and evolution, 33, (9), 2016, p2368-2375 , Journal Article, PUBLISHED  DOI

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Computational Tools and Resources in Plant Genome Informatics. in, editor(s)Paul Christou and Harry Klee , Handbook of Plant Biotechnology, Wiley, 2004, pp1 - 28, [Vision, T.J. and McLysaght, A.], Book Chapter, PUBLISHED


Award Date
European Research Council (ERC) Consolidator Award 2017
JBS Haldane Prize Lectures (Genetics Society UK) 2016
Selected for portrait in RIA as part of Women on Walls project: 2016
European Research Council (ERC) Starting Researcher Award 2013-2018
President of Ireland Young Researcher's Award (Science Foundation Ireland) 2005
Research in my lab focuses on comparative genomics of vertebrates. We aim to uncover and understand fundamental principles of genome evolution, and, where possible, to relate these to interpretation of human pathogenic mutations. Two primary research interests are de novo gene evolution and gene and genome duplication. We found the first ever examples of de novo genes in the human genome (Knowles & McLysaght, 2009). De novo origin of genes had previously been proposed for a handful of cases in Drosophila, rice and yeast, but key to the impact of our paper was the careful exclusion of all trivial and competing hypotheses for the origin of these genes. Since 2009 the field of de novo gene evolution has grown but I felt that big questions and unifying models of evolution were lacking. In order to provide these, I co-wrote a perspectives piece with for Nature Reviews Genetics (McLysaght & Hurst, 2016) where we identified key challenges and presented a novel hypothesis on the role of antagonistic co-evolution in the origin of new genes and suggested how this could explain the observed involvement of new genes in cancer. We have a long track-record working on evolutionary gene duplication. Recently this has centred on the problem of dosage sensitivity and how this impacts on duplicability and disease. In particular, we have focused on duplicate genes retained after whole genome duplication (ohnologs). We found the first evidence for dosage constraints on ohnologs and linked that to involvement in human disease (Makino & McLysaght, PNAS 2010). We have pioneered the integration of evolutionary analysis into the interpretation and understanding of human copy number variants (CNVs). We found a very clear pattern of evolutionary copy number conservation (evolutionary dosage constraint) for genes in pathogenic CNVs. Based on this work we have found genome-wide support for dosage sensitivity as a primary driver of CNV pathogenicity, and also by integrating CNV and evolutionary data have generated a list of candidate genes for human pathogenic CNVs (Rice & McLysaght, Nature Communications 2017). Additionally, because of the strong link that we discovered between ohnologs and dosage sensitivity and disease, we recognised the great need for a landmark analysis of the whole genome duplications (WGD) at the base of the vertebrate lineage. Such ancient events are difficult to reconstruct and interpret, and to date most studies exclude large fractions of the genome due to uncertainty. We have pioneered a radically new approach to the reconstruction of the ancient WGD (Nakatani & McLysaght, 2017) which applies topic probability models (originally devised for document analysis) to the problem of ancestral genome reconstruction. My international standing in the field is demonstrated by invitations to join international collaborations, my appointment to leadership roles within several journals and international societies (notably I am President of SMBE 2018-20), invitations to give talks at major international conferences, my organisational role in several international meetings and workshops, my publication record in top journals, and my success in winning competitive research funding (totalling over €4.8 million).