Inferring the Rate and Time-Scale of Dengue Virus Evolution
Open accessAbstract
Dengue is often referred to as an emerging disease because of the rapid increases in incidence and prevalence that have been observed in recent decades. To understand the rate at which genetic diversification occurs in dengue virus and to infer the time-scale of its evolution, we employed a maximum likelihood method that uses information about times of virus sampling to estimate the rate of molecular evolution in a large number of viral envelope (E) gene sequences and to place bounds around the dates of appearance of all serotypes and specific genotypes. Our analysis reveals that dengue virus generally evolves according to a molecular clock, although some serotype-specific and genotype-specific rate differences were observed, and that its origin is more recent than previously suggested, with the virus appearing approximately 1,000 years ago. Furthermore, we estimate that the zoonotic transfer of dengue from sylvatic (monkey) to sustained human transmission occurred between 125 and 320 years ago, that the current global genetic diversity in the four serotypes of dengue virus only appeared during the past century, and that the recent rise in genetic diversity can be loosely correlated both to human activities such as population growth, urbanization, and mass transport and to the emergence of dengue hemorrhagic fever as a major disease problem.
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For some viruses, such as Dengue fever or influenza, observable constancy of rates provides a convincing molecular clock.
“For some viruses - such as Dengue fever 63 or influenza 65 - observable constancy of rates provides a convincing molecular clock.”
From The modern molecular clock (2003) · cites this paper as [63]
If many calibration dates are available, it becomes possible to test the constancy of rates across the viral phylogeny.
“If many calibration dates are available - for example, if a series of samples from a single infected patient 62 or a collection of archived samples 63 is available - it becomes possible to test the constancy of rates across the viral phylogeny.”
From The modern molecular clock (2003) · cites this paper as [63]
Viral molecular clocks are most commonly calibrated using past samples, such as sequences from stored tissue samples.
“Viral molecular clocks are most commonly calibrated using past samples, such as sequences from stored tissue samples 2,63 .”
From The modern molecular clock (2003) · cites this paper as [63]
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- Authors
- Twiddy, S. S., Holmes, E. C., & Rambaut, A.
- Affiliations
- University of Oxford (GB)
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-01
- Volume
- 20
- Issue
- 1
- Pages
- 122-129
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2145462455
- Cited by
- 269
- References
- 26
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 14 · 2022: 3 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 13 · 2017: 11 · 2016: 7 · 2015: 7 · 2014: 17 · 2013: 13 · 2012: 19
- FWCI
- 10.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Biology and Evolution (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Royal Society
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic diversity and population structure
- Keywords
- dengue virus, molecular clock, molecular evolution rate, viral envelope gene, zoonotic transmission, genetic diversity, dengue hemorrhagic fever, emerging infectious diseases, time-scaled phylogeny
- MeSH terms
- Animals, Dengue Virus, Genotype, Humans, Mutation, Phylogeny, Likelihood Functions, Evolution, Molecular
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