On the analysis of intrahost and interhost viral populations

Human cytomegalovirus as a case study of pitfalls and expectations

Nicholas Renzette, Susanne Pfeifer, Sebastian Matuszewski, Timothy F. Kowalik, Jeffrey Jensen

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Intrahost and interhost assessments of viral diversity are often treated as measures of separate and distinct evolutionary processes, with numerous investigations reporting seemingly incompatible results between the two. For example, in human cytomegalovirus, the nucleotide diversity estimates are 10-fold higher for interhost data, while the number of segregating (i.e., polymorphic) sites is 6-fold lower. These results have been interpreted as demonstrating that sampled intrahost variants are strongly deleterious. In reality, however, these observations are fully consistent with standard population genetic expectations. Here, we analyze published intra- and interhost data sets within this framework, utilizing statistical inference tools to quantify the fitness effects of segregating mutations. Further, we utilize population level simulations to clarify expectations under common evolutionary models. Contrary to common claims in the literature, these results suggest that most observed polymorphisms are likely nearly neutral with regard to fitness and that standard population genetic models in fact well predict observed levels of both intra- and interhost variability.

Original languageEnglish (US)
Article numbere01976-16
JournalJournal of Virology
Volume91
Issue number5
DOIs
StatePublished - 2017

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Human herpesvirus 5
Population Genetics
Cytomegalovirus
population genetics
case studies
Genetic Models
Population
Nucleotides
nucleotides
genetic polymorphism
mutation
Mutation
Datasets

Keywords

  • Human cytomegalovirus
  • Interhost diversity
  • Intrahost diversity
  • Population genetics

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

On the analysis of intrahost and interhost viral populations : Human cytomegalovirus as a case study of pitfalls and expectations. / Renzette, Nicholas; Pfeifer, Susanne; Matuszewski, Sebastian; Kowalik, Timothy F.; Jensen, Jeffrey.

In: Journal of Virology, Vol. 91, No. 5, e01976-16, 2017.

Research output: Contribution to journalArticle

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