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Aoife Mc Lysaght
Professor, Genetics

Publications and Further Research Outputs

Peer-Reviewed Publications

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, 2019 DOI

Vakirlis, N. and Monerawela, C. and McManus, G. and Ribeiro, O. and McLysaght, A. and James, T. and Bond, U., Evolutionary journey and characterisation of a novel pan-gene associated with beer strains of Saccharomyces cerevisiae, Yeast, 36, (7), 2019, p425-437 Journal Article, 2019 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, p1816-1818 Journal Article, 2019

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, 2018 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, 2018 DOI

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 Journal Article, 2018 DOI

Rice A., McLysaght A., Dosage sensitivity is a major determinant of human copy number variant pathogenicity, Nature Communications, 8, 2017, p14366 Journal Article, 2017 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, 2017 URL DOI

Rice A.M, McLysaght A, Dosage-sensitive genes in evolution and disease, BMC Biology, 15, (1), 2017, p78- Journal Article, 2017 URL DOI TARA - Full Text

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 Journal Article, 2016 URL DOI

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, 2016 DOI

Guerzoni D, McLysaght A., De Novo Genes Arise at a Slow but Steady Rate along the Primate Lineage and Have Been Subject to Incomplete Lineage Sorting., Genome biology and evolution, 8, (4), 2016, p1222-1232 Journal Article, 2016 DOI

McLysaght A, Guerzoni D, New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation., Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 370, (1678), 2015 Journal Article, 2015 DOI

Brien GL, Healy E, Jerman E, Conway E, Fadda E, O'Donovan D, Krivtsov AV, Rice AM, Kearney CJ, Flaus A, McDade SS, Martin SJ, McLysaght A, O'Connell DJ, Armstrong SA, Bracken AP, A chromatin-independent role of Polycomb-like 1 to stabilize p53 and promote cellular quiescence., Genes & Development, 29, (21), 2015, p2231-43 Journal Article, 2015 DOI TARA - Full Text

McLysaght A, Makino T, Grayton HM, Tropeano M, Mitchell KJ, Vassos E, Collier DA, Ohnologs are overrepresented in pathogenic copy number mutations., Proceedings of the National Academy of Sciences of the United States of America, 111, (1), 2014, p361-6 Journal Article, 2014

Makino T, McLysaght A, Kawata M, Genome-wide deserts for copy number variation in vertebrates., Nature communications, 4, 2013, p2283 Journal Article, 2013

Bratke KA, McLysaght A, Rothenburg S, A survey of host range genes in poxvirus genomes., Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 14, 2013, p406-425 Journal Article, 2013 DOI TARA - Full Text

Pessia E, Makino T, Bailly-Bechet M, McLysaght A, Marais GA, Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome., Proceedings of the National Academy of Sciences of the United States of America, 109, (14), 2012, p5346-5351 Journal Article, 2012 DOI TARA - Full Text

Murphy DN, McLysaght A, De novo origin of protein-coding genes in murine rodents., PloS one, 7, (11), 2012, pe48650 Journal Article, 2012 TARA - Full Text DOI

Makino T, McLysaght A, Positionally biased gene loss after whole genome duplication: evidence from human, yeast, and plant., Genome research, 22, (12), 2012, p2427-2435 Journal Article, 2012 TARA - Full Text DOI

Murphy, D.N., McLysaght, A., De Novo Origin of Protein-Coding Genes in Murine Rodents, PLoS ONE, 7, (11), 2012 Journal Article, 2012

Satake M, Kawata M, McLysaght A, Makino T, Evolution of Vertebrate Tissues Driven by Differential Modes of Gene Duplication., DNA research : an international journal for rapid publication of reports on genes and genomes, 19, (4), 2012, p305-316 Journal Article, 2012 DOI TARA - Full Text

Daniele Guerzoni, Aoife McLysaght, De Novo Origins of Human Genes, PLoS Genetics, 7, (11, e1002381), 2011 Journal Article, 2011 TARA - Full Text

Pérez-Bercoff Å, McLysaght A, Conant GC, Patterns of indirect protein interactions suggest a spatial organization to metabolism., Molecular bioSystems, 7, (11), 2011, p3056-3064 Journal Article, 2011 DOI

Pérez-Bercoff A, Makino T, McLysaght A, Duplicability of self-interacting human genes., BMC Evolutionary Biology, 10, (160), 2010 Journal Article, 2010 TARA - Full Text DOI

Makino, T. McLysaght, A., Ohnologs in the human genome are dosage balanced and frequently associated with disease, Proceedings of the National Academy of Sciences of the United States of America , 107, (20), 2010, p9270-9274 Journal Article, 2010 TARA - Full Text

Knowles, DG, McLysaght, A, Recent de novo origin of human protein-coding genes., Genome Research, 19, (10), 2009, p1752-1759 Journal Article, 2009 DOI TARA - Full Text

Evolutionary Analyses of Protein Interaction Networks in, editor(s)Xiao-Li Li, See-Kiong Ng , Biological Data Mining in Protein Interaction Networks, United States, IGI Global, 2009, [Makino, T. and McLysaght, A.] Book Chapter, 2009

Functional divergence of duplicated genes in, editor(s)Dittmar de la Cruz, K. and Liberles, D. , Evolution After Gene Duplication, Wiley, 2009, [Makino, T. Knowles D.G. and McLysaght, A.] Book Chapter, 2009

Makino, T, Hokamp, K, McLysaght, A, The complex relationship of gene duplication and essentiality., Trends in genetics, 25, (4), 2009, p152 - 155 Journal Article, 2009 DOI TARA - Full Text

The Evolution of Functional Gene Clusters In Eukaryote Genomes in, editor(s)Pierre Pontarotti , Evolutionary Biology: Concept, Modeling and Application, Springer, 2009, pp185 - 194, [Makino, T., and McLysaght, A.] Book Chapter, 2009

Bratke, K.A. and McLysaght, A., Identification of multiple independent horizontal gene transfers into poxviruses using a comparative genomics approach, BMC Evolutionary Biology, 8, (67), 2008, p[1-13] Journal Article, 2008 URL TARA - Full Text DOI

Aoife McLysaght, Evolutionary steps of sex chromosomes are reflected in retrogenes, Trends in Genetics, 24, (10), 2008, p478 - 481 Journal Article, 2008 TARA - Full Text

Makino, T, McLysaght, A, Interacting gene clusters and the evolution of the vertebrate immune system., Molecular Biology and Evolution, 25, (9), 2008, p1855 - 1862 Journal Article, 2008 TARA - Full Text URL DOI

Knowles D. G. and McLysaght A., High Rate of Recent Intron Gain and Loss in Simultaneously Duplicated Arabidopsis genes, Molecular Biology and Evolution, 23, (8), 2006, p1548 - 1557 Journal Article, 2006 URL TARA - Full Text DOI

Aoife McLysaght, Daniel H. Huson (Eds.), Comparative Genomics, Germany, Springer, 2005, 1 - 166pp Book, 2005 URL

McLysaght, A., Huson, D., Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics): Preface, Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 3678 LNBI, 2005 Journal Article, 2005

Pollastri, G. and McLysaght, A., Porter: a new, accurate server for protein secondary structure prediction, Bioinformatics, 21, (8), 2005, p1719 - 1720 Journal Article, 2005 URL TARA - Full Text DOI

Trinh, P., McLysaght, A., Sankoff, D., Genomic Features in the Breakpoint Regions between Syntenic Blocks, Bioinformatics, 20 Suppl 1, 2004, pi318 - i325 Journal Article, 2004 URL TARA - Full Text DOI

Hampson, S., McLysaght, A., Gaut, B.S., Baldi, P.F., LineUp: Statistical Detection of Chromosomal Homology with Application to Plant Comparative Genomics, Genome Research, 13, (5), 2003, p999 - 1010 Journal Article, 2003 DOI URL TARA - Full Text

Hokamp, K., McLysaght, A. and Wolfe, K. H., The 2R hypothesis and the human genome sequence., Journal of Structural and Functional Genomics, 3, (1-4), 2003, p95 - 110 Journal Article, 2003 URL DOI

McLysaght, A., Baldi, P.F., Gaut, B.S., Extensive gene gain associated with adaptive evolution of poxviruses, Proceedings of the National Academy of Sciences, USA, 100, (26), 2003, p15655 - 15660 Journal Article, 2003 TARA - Full Text DOI URL

McLysaght, A., Hokamp K, and Wolfe, K.H., Extensive genomic duplication during early chordate evolution, Nature Genetics, 31, (2), 2002, p200 - 204 Journal Article, 2002 DOI URL

Aoife McLysaght, Evolution of Vertebrate Genome Organisation., University of Dublin, Trinity College, 2001 Thesis, 2001 URL

Lander, E.S., McLysaght, A., et al., Initial sequencing and analysis of the human genome., Nature, 490, 2001, p860-921 Journal Article, 2001 URL

High frequency of inversions during eukaryote gene order evolution in, Comparative Genomics: Empirical and Analytical Approaches to Gene Order Dynamics, Map Alignment and the Evolution of Gene Families, Dordrecht., Kluwer Academic Press, 2000, pp47 - 58, [McLysaght, A., Seoighe, C. and Wolfe, K.] Book Chapter, 2000

McLysaght, A., Enright, A.J., Skrabanek, L. & Wolfe, K.H. , Estimation of synteny conservation and genome compaction between pufferfish (Fugu) and human., Yeast , 17, 2000, p22-36. Journal Article, 2000 URL TARA - Full Text DOI

Non-Peer-Reviewed Publications

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, 2004

Research Expertise

Description

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).

Projects

  • Title
    • Gene expression level as a keystone to understanding gene duplication: evolutionary constraints, opportunities, and disease
  • Funding Agency
    • ERC
  • Date From
    • 01/01/2019
  • Date To
    • 30/12/2023
  • Title
    • SFI ERC Supplement
  • Funding Agency
    • SFI
  • Date From
    • 01/01/2019
  • Date To
    • 30/12/2023
  • Title
    • Dosage-sensitive genes in evolution and disease
  • Funding Agency
    • European Research Council
  • Date From
    • Jan 2013
  • Date To
    • Dec 3017
  • Title
    • Origin and Evolution of Vertebrate de novo Genes
  • Funding Agency
    • Science Foundation Ireland
  • Date From
    • 2010
  • Date To
    • 2014
  • Title
    • Gene Gains, Losses and Relocations during Vertebrate Evolution
  • Funding Agency
    • Science Foundation Ireland
  • Date From
    • October 2005
  • Date To
    • September 2010
  • Title
    • The Origin of New Genes in Poxviruses
  • Funding Agency
    • IRCSET
  • Date From
    • October 2005
  • Date To
    • September 2008

Keywords

ACCELERATED SEQUENCE EVOLUTION; ANCIENT; Biocomputing; BIOINFORMATICS; COEVOLUTION; COMPARATIVE GENOMICS; COMPLETE NUCLEOTIDE-SEQUENCE; CONCERTED EVOLUTION; Evolution; EVOLUTION RATE; Evolutionary Biology; EVOLUTIONARY CHANGES; EVOLUTIONARY RELATIONSHIPS; EVOLUTIONARY SIGNIFICANCE; GENES; Genetics; Genomes, Genomics; Genomics; HIGH-FREQUENCY RETROTRANSPOSITION; Human Evolution; HYPOTHESIS; LINKAGE; Molecular evolution; Molecular Genetics; MONOAMINE-OXIDASE-A; PATTERN; POLYPLOIDS; RECEPTOR; SEQUENCE; VERTEBRATE EVOLUTION

Recognition

Representations

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

Awards and Honours

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: https://www.ria.ie/women-walls-0 2016

European Research Council (ERC) Starting Researcher Award 2013-2018

President of Ireland Young Researcher's Award (Science Foundation Ireland) 2005

Memberships

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