Leveraging genomic and genetic diversity to gain insights into viral evolution and spread Público

Abstract

As viral pathogens replicate within host species, errors by the viral polyermase introduce differences between the original and replicated genomes. Even when these errors do not alter viral function, their accumulation over time leaves characteristic patterns representative of the biological context in which they arose. Fitting quantitative models to these data provides a way for researchers to interrogate these patterns. Here, we analyze influenza A and SARS- CoV-2 sequence data to better understand the dynamics of these pathogens across biological scales. We show that the within- ost evolution of influenza genomic diversity is highly stochastic, that transmission bottlenecks of SARS-CoV-2 between hosts are extremely small, and that population level SARS-CoV-2 transmission is characterized by rapid undetected geographic dispersion and a high degree of transmission heterogeneity between infected hosts. Our results as a whole add to the growing body of literature regarding the ecology and evolution of human RNA viruses and in particular highlight how these populations are shaped by cross-scale dynamics.

Table of Contents

1 Introduction

1.1 Generation of viral diversity 1.2 Processes which shape viral diversity 1.3 Characterizing viral diversity 1.4 Cross-scales analysis of acute viral diversity

2 Leveraging genomic diversity to gain insights into within host influenza dynamics

2.1 Abstract 2.2 Introduction 2.3 Materials and methods 2.3.1 Data source 2.3.2 Transmission analyses 2.3.3 DVG identification 2.3.4 DVG quality filtering 2.3.5 BlastN analysis 2.3.6 Statistical analyses and visualization 2.4 Results 2.4.1 Limited DVGs in plasmid controls 2.4.2 DVGs observed readily in clinical samples 2.4.3 Nearly ubiquitous NS DVG 2.4.4 DVG populations are dynamic 2.4.5 Limited evidence for the transmission of DVGs 2.5 Discussion 2.6 Supplementary 2.6.1 Supplementary Figures 2.6.2 SupplementaryTables 3 Insights from SARS-CoV-2 sequences 3.1 M.A.M Contributions 3.2 Published Manuscript 4 Comment on “Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2” 4.1 M.A.M Contributions 4.2 Published Manuscript 4.3 Supplement 5 Full genome viral sequences inform patterns of SARS-CoV-2 spread into and within Israel 5.1 M.A.M. Contributions 5.2 PublishedManuscript 5.3 Supplement 6 Unrecognized introductions of SARS-CoV-2 into the US state of Georgia shaped the early epidemic 6.1 M.A.M. Contributions 6.2 Published Manuscript 6.3 Supplement

7 Discussion

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Population Biology, Ecology & Evolution
Degree	Ph.D.
Submission	Dissertation
Language	English
Research Field	Biology, Evolution and Development Biology, Ecology Biology, Bioinformatics
Palavra-chave	ecology epidemiology SARS-CoV-2 virus evolutionary biology influenza infectious diseases
Committee Chair / Thesis Advisor	Katharina Koelle, Emory University
Committee Members	Anne Piantadosi, Emory University Anice Lowen, Emory University Timothy Read, Emory University Daniel Weissman, Emory University

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