Authors: Dearborn DC, Gager AB, McArthur AG, Gilmour ME, Mandzhukova E, Mauck RA.
Mol Ecol. 2016 Sep;25(17):4355-67.
Genes of the major histocompatibility complex (MHC) exhibit heterozygote advantage in immune defence, which in turn can select for MHC-disassortative mate choice. However, many species lack this expected pattern of MHC-disassortative mating. A possible explanation lies in evolutionary processes following gene duplication: if two duplicated MHC genes become functionally diverged from each other, offspring will inherit diverse multilocus genotypes even under random mating. We used locus-specific primers for high-throughput sequencing of two expressed MHC Class II B genes in Leach’s storm-petrels, Oceanodroma leucorhoa, and found that exon 2 alleles fall into two gene-specific monophyletic clades. We tested for disassortative vs. random mating at these two functionally diverged Class II B genes, using multiple metrics and different subsets of exon 2 sequence data. With good statistical power, we consistently found random assortment of mates at MHC. Despite random mating, birds had MHC genotypes with functionally diverged alleles, averaging 13 amino acid differences in pairwise comparisons of exon 2 alleles within individuals. To test whether this high MHC diversity in individuals is driven by evolutionary divergence of the two duplicated genes, we built a phylogenetic permutation model. The model showed that genotypic diversity was strongly impacted by sequence divergence between the most common allele of each gene, with a smaller additional impact of monophyly of the two genes. Divergence of allele sequences between genes may have reduced the benefits of actively seeking MHC-dissimilar mates, in which case the evolutionary history of duplicated genes is shaping the adaptive landscape of sexual selection.
A cross-national research consortia co-led by McMaster’s Andrew McArthur is receiving two of 16 federal grants to further develop a big data solution to the growing problem of antimicrobial resistance (AMR). The government’s investment, totaling more than $4M, is the result of Genome Canada’s 2015 Bioinformatics and Computational Biology Competition, a partnership with the Canadian Institutes of Health Research (CIHR). McArthur and his colleagues will receive $500,000 over two years. McArthur will work closely with researchers from the University of British Columbia, Simon Fraser University, Dalhousie University and the Public Health Agency of Canada to design and develop novel software and database systems that will empower public health agencies and the agri-food sector to rapidly respond to threats posed by infectious disease outbreaks and food-borne illnesses.
Full Coverage: Faculty of Health Sciences, Genome Canada, Newswire, Hamilton Spectator
Biochem 3R06 Project Students – Arjun Sharma
BiomedDC 4A15 Thesis Students – Kirill Pankov, Suman Virdee, Annie Cheng, Jonsson Liu, Godwin Chan
Kara Tsang (graduate, McMaster BDC) – Kara did her BiomedDC 4A15 thesis in the lab, focused on Pseudomonas resistome prediction and cystic fibrosis-associated metagenomic sequencing and starts September 2016 as MSc student in the area of clinical AMR analytics, particularly metagenomics. Her work will be part of our recently funded Genome Canada grants, as well as part of McMaster’s clinical genome sequencing efforts.
Krishna Srinivasan (graduate, McMaster Biology) – Krishna just finished his undergraduate degree in McMaster’s Biology department, with a thesis in environmental toxicology. He starts as a MSc student September 2016, collaborating with the Jenny lab (UAlabama) on our recently funded NIH grant examining the role of MTF-1 in lens development and cataractogenesis.
The McArthur Lab bids farewell and good luck to Biren Dave and Sachin Doshi! Sachin left mid-summer for a fellowship at Harvard and now is off to the UToronto Medical School! Biren finished his 3rd year Biochemistry Co-Op position and joins McMaster’s Stem Cell and Cancer Research Institute for his fourth year thesis. Thanks to you both!
McArthur, A.G., B. Jia, A.R. Raphenya, P. Guo, K. Tsang, B. Dave, B. Alcock, B. Lago, N. Waglechner, & G.D. Wright. 2016. The Comprehensive Antibiotic Resistance Database – A Platform for Antimicrobial Resistance Surveillance. Invited presentation at the 2nd Conference Rapid Microbial NGS and Bioinformatics: Translation Into Practice, Hamburg, Germany.
Antimicrobial resistance (AMR) is among the most pressing public health crises of the 21st Century. Despite the importance of resistance to health, this field has been slow to take advantage of genome scale tools. Phenotype based criteria dominate the epidemiology of antibiotic action and effectiveness. There is a poor understanding of which antibiotic resistance genes are in circulation, which a threat, and how clinicians and public health workers can manage the crisis of resistance. However, DNA sequencing is rapidly decreasing in cost and as such we are on the cusp of an age of high-throughput molecular epidemiology. What are needed are tools for rapid, accurate analysis of DNA sequence data for the genetic underpinnings of antibiotic resistance. In an effort to address this problem, we have created the Comprehensive Antibiotic Resistance Database (card.mcmaster.ca). This database is a rigorously curated collection of known antibiotics, targets, and resistance determinants. It integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in raw genome sequences using the novel Resistance Gene Identifier (RGI). Here we review the current state of the CARD, particularly recent advances in the curation of resistance determinants and the structure of the ARO. We will also present our plans for development of semi- and fully-automated text mining algorithms for curation of broader AMR data, construction of meta-models for improved AMR phenotype prediction, and release of portable command-line genome analysis tools.
* presenter underlined, trainees in bold
CIHR (G. Steinberg, McMaster University, Canada) Gene Environment Team on Brown/beige Adipose Tissue (GET_BAT). In this project we will conduct studies in cells, mice and humans to examine how agricultural and food processing practices may regulate brown adipose tissue metabolic activity directly or indirectly by altering the billions of bacteria that reside within our gastrointestinal tract.
NIH/NIEHS (M. Jenny, University of Alabama, USA) The role of MTF-1 as a mediator of ocular toxicity. The major goals of this project are to characterize the role of MTF-1 in regulating genes involved in eye development.
NIH/NIEHS (A. Timme-Laragy, University of Massachusetts Amherst) Activation of Nrf2 during embryonic development: mechanisms and consequences. Examining the possible regulatory role of Nrf2 in early embryonic development, with emphasis upon molecular responses to oxidative stress.
McMaster Interdisciplinary Research Exposition (MIREx); Ontario Biology Day; Biomedical Discovery and Commercialization Engage Symposium; Rapid Microbial NGS and Bioinformatics: Translation Into Practice (Germany); Canadian Food Inspection Agency Forum on Genomics and Antimicrobial Resistance; New Antibacterial Discovery & Development Gordon Research Conference (Italy); McMaster Women in Science and Engineering (WISE) Current Research in Engineering, Science & Technology (CREST) Meeting; 6th Biennial National IDeA Symposium of Biomedical Research Excellence (USA).
Presenter underlined, trainees in bold.
- Dave, B.M., J.A. Klein, L.A. Knodler, A.R. Raphenya, & A.G. McArthur. 2016. A phylogenetic analysis of Inv/Mxi-Spa proteins and implications for functional complementation. Poster presentation at McMaster Interdisciplinary Research Exposition (MIREx), Hamilton, Ontario, Canada.
- Dave, B.M., J.A. Klein, L.A. Knodler, A.R. Raphenya, & A.G. McArthur. 2016. A phylogenetic analysis of Inv/Mxi-Spa proteins and implications for functional complementation. Poster presentation at Ontario Biology Day 2016, Toronto, Ontario, Canada.
- Lin, Z. & A.G. McArthur. 2016. Adapting Galaxy bioinformatics to outbreak-associated Clostridium difficile. Poster presentation at McMaster’s Biomedical Discovery and Commercialization Engage Symposium, Hamilton, Ontario, Canada.
- McArthur, A.G., B. Jia, A.R. Raphenya, P. Guo, K. Tsang, B. Dave, B. Alcock, B. Lago, N. Waglechner, & G.D. Wright. 2016. The Comprehensive Antibiotic Resistance Database – A Platform for Antimicrobial Resistance Surveillance. Invited presentation at the 2nd Conference Rapid Microbial NGS and Bioinformatics: Translation Into Practice, Hamburg, Germany.
- McArthur, A.G. 2016. Bioinformatic resources for antimicrobial resistance. Invited presentation at Canadian Food Inspection Agency (CFIA) Forum on Genomics and Antimicrobial Resistance, Ottawa, Ontario, Canada.
- McArthur, A.G. 2016. Combatting Antibiotic Resistance Using Surveillance. Invited presentation at McMaster Interdisciplinary Research Exposition (MIREx), Hamilton, Ontario, Canada.
- Pawlowski, A.C., W. Wang, K. Koteva, H.A. Barton, B. Jia, A.R. Raphenya, P. Guo, A.G. McArthur, G.D. Wright. 2016. A multi-antibiotic resistant genotype is maintained for millions of years. Presentation at the New Antibacterial Discovery & Development Gordon Research Conference, Lucca, Italy.
- Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at McMaster Interdisciplinary Research Exposition (MIREx), Hamilton, Ontario, Canada.
- Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at Ontario Biology Day 2016, Toronto, Ontario, Canada.
- Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at McMaster Women in Science and Engineering (WISE) Current Research in Engineering, Science & Technology (CREST) Meeting, Hamilton, Ontario, Canada.
- Tsang, K. & A.G. McArthur. 2016. Translation of biocuration to metagenomic analysis. Poster presentation at McMaster’s Biomedical Discovery and Commercialization Engage Symposium, Hamilton, Ontario, Canada.
- Williams, L., A.G. McArthur, B. Lago, A.R. Raphenya, N. Pray, N. Saleem, S. Salas, K. Paulson, R. Mangar, Y. Liu, A. Vo, & J. Shavit. 2016. Nuclear factor, erythoid 2 (Nfe2) is a transcriptional regulator of oxidative stress during zebrafish development. Presentation at the 6th Biennial National IDeA Symposium of Biomedical Research Excellence, Washington, DC.
Ten undergraduate students from the faculties of Science and Health Sciences have been awarded the prestigious Michael G. DeGroote Institute for Infectious Disease Research (IIDR) Summer Student Fellowship, including our own Briony Lago (third from the right). This highly competitive fellowship, now in its fourth year and worth $1,000, is designed to support students working in the labs of IIDR members during their summer practicum, which runs from May to August. Briony Lago joined the lab as part of her McMaster Chemical Biology Co-Op program, working on our ‘Omic’ Responses & Inactivity in Aging project (a collaboration with colleagues in Kinesiology & Chemistry), our collaboration with Bates College on the role of Nfe2 in oxidative stress response during zebrafish development, and biocuration of our Comprehensive Antibiotic Resistance Database.