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Molecular Phylodynamics and Protein Modeling of Infectious Salmon Anemia Virus (ISAV). Eduardo Castro-Nallar Brigham Young University Provo, Utah. Introduction. Most cases is lethal to samonids , specially adult atlantic salmon ISAV is a member of the Orthomyxoviridae family.
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Molecular Phylodynamics and Protein Modeling of Infectious Salmon Anemia Virus (ISAV) • Eduardo Castro-Nallar • Brigham Young University • Provo, Utah
Introduction • Most cases is lethal to samonids, specially adult atlantic salmon • ISAV is a member of the Orthomyxoviridae family. • (-)ss RNA, 8 segments, 2 surface glycoproteins. • Hemagluttinin-esterase (400aa) and fusion (444aa). • It is present in Europe, North America and Chile. Represents a threat to aquaculture worldwide.
Motivation • To investigate ISAV population dynamics and origins in the 2007 Chilean outbreak. • To show the suitability of phylogenetic and phylodynamic methods to epidemiological surveillance programs.
Questions 1) whether recombination is a relevant force acting on both surface ISAV genes. 2) whether age estimates agree with epidemiological data. 3) whether population processes leave marks on ISAV genomes that allows us to reconstruct its demographic history.
Recombination and Genetic diversityIs recombination a driving force in ISAV evolution?
Which population is older? low overall recombination force (r) of [1.173 × 10-3 (1.90 × 10-4 - 3.50 × 10-3)] Mary K. Kuhner. LAMARC 2.0: maximum likelihood and Bayesian estimation of population parameters. Bioinformatics (2006) 22(6): 768-770.
Recombination breakpoints HE gene HPR: Highly polymorphic region near 3’. Virulence determinant? Darren P. Martin, Philippe Lemey, Martin Lott, Vincent Moulton, David Posada, and Pierre Lefeuvre RDP3: a flexible and fast computer program for analyzing recombination. Bioinformatics (2010) 26(19): 2462-2463.
Norwegian population is older. Chilean population is less diverse. • Recombination is rare but occurs • Recombination occurs near the HPR
Evolutionary relationships How many introductions to the Chilean population had occurred? or Is the Chilean clade monophyletic? Drummond AJ, Rambaut A: BEAST: Bayesian evolutionary analysis bysampling trees. BMC Evol Biol 2007, 7(1):214.
He gene Reassortment
Outbreak ISAV was introduced probably once • Reassortment between segments is present • Substitution rates agree with others – ss RNA viruses • ISAV was introduced in Chile around 2001 • HPR0 was probably the precursor of the Chilean outbreak
Population dynamicsIs there any signal of a population bottleneck? Drummond AJ, Rambaut A: BEAST: Bayesian evolutionary analysis bysampling trees. BMC Evol Biol 2007, 7(1):214.
Population size simulations agree with known epidemiological data, i.e. 2007
Are any amino acids under positive selection? dN/dS > 1 Sergei L. Kosakovsky Pond, Simon D. W. Frost, and Spencer V. Muse. HyPhy: hypothesis testing using phylogenies. Bioinformatics (2005) 21(5): 676-679 first published online October 27, 2004
HE gene Before HPR: 340 134
130, 170, and 279 279: lies immediately downstream of insertions Fusion
Positively selected sites are found near potential virulence factors
Acknowledgements Crandall Lab at BYU Centro de Biotecnología Acuícola Laboratorio de Virología – USACH Marcelo Cortez, Carolina Mascayano and Keith Crandall Castro-Nallar, E., Martin, M. C.-S., Mascayano, C., Molina, C., & Crandall, K. A. (2011). Molecular phylodynamics and protein modeling of infectious salmon anemia virus (ISAV). BMC Evolutionary Biology, 11(1), 349. BioMed Central Ltd. doi:10.1186/1471-2148-11-349