WOM LAB | Dengue

Dengue is caused by a mosquito-borne virus that infects people throughout the tropics. Infection with the virus results in a severe flu-like illness that occasionally progresses to hemorrhaging, shock, and death. The virus, a relative to Yellow Fever, West Nile, and Japanese Encephalitis, exists as four separate serotypes that each generates a unique immune response. In the last twenty years, the incidence of dengue fever has increased 100-fold world-wide and hyperendemic transmission (more than one serotype circulation at the same time) now characterizes most tropical countries, including Puerto Rico.

Our research, in collaboration with the CDC, CAREC and Oxford University, seeks to understand the connection between high mutation rates, genetic change, and disease pathogenesis. We use comparative longitudinal phylogenetic approaches to track viral genetic change since the establishment of epidemic dengue in Puerto Rico in the 1980's. These data allow us to (1) correlate population genetic changes with cycles of endemic and epidemic transmission; (2) explore the nature of selection acting on different viral gene regions; (3) identify potentially significant amino acid positions and determine their association with disease severity and/or transmission potential; and (4) evaluate the importance of recombination in the evolution of the dengue virus in PR. Our results to date demonstrate that: (1) dengue serotype 4 evolves throughout the Caribbean somewhat independently for a given island, with the occasional infusion of variants from other islands as a function of proximity and other socio-geographic factors (Foster et al., 2003). (2) the history of dengue-4 populations in PR is characterized by striking lineage turnover correlated, driven in part by selection on a nonstructural gene, NS2A (Bennett et al., 2003 ). (3) dengue serotype 2 and 4 indicates are evolving in different ways, the former marked by less lineage turnover, changing evolutionary rates, and more changes in the structural regions (in prep). Future directions include expanding comparative studies between serotypes to include more gene regions and more geographic locations. Improved understanding of the role of viral evolution in disease dynamics will ultimately contribute to the development of evolutionary-based strategies for the control of this infectious disease.

Applied Research in Ecology and Evolutionary Biology
We are a large and active research program directed at more applied questions in ecology and evolution. Specific projects are cross-disciplinary in scope, involving collaborations with the Centers For Disease Control and Prevention, Caribbean Epidemiology Centre, Oxford University Evolution Group, and the PR-Department of Natural Resources. Current projects range from managing threatened marine resources to studying the forces driving dengue viral evolution in the Caribbean. In addition, we recently founded, with funds from NSF, the Molecular Ecology, Evolution and Genetics Program (MEEG) under the auspices of the newly created Center for Applied Tropical Ecology and Conservation. Some specific research areas include:

The evolutionary history of emergent dengue in the Carribbean
Dengue is caused by a mosquito-borne virus that infects people throughout the tropics. Infection with the virus results in a severe flu-like illness that occasionally progresses to hemorrhaging, shock, and death. The virus, a relative to Yellow Fever, West Nile, and Japanese Encephalitis, exists as four separate serotypes that each generates a unique immune response. In the last twenty years, the incidence of dengue fever has increased 100-fold world-wide and hyperendemic transmission (more than one serotype circulation at the same time) now characterizes most tropical countries, including Puerto Rico. Our research, in collaboration with the CDC, CAREC and Oxford University, seeks to understand the connection between high mutation rates, genetic change, and disease pathogenesis. We use comparative longitudinal phylogenetic approaches to track viral genetic change since the establishment of epidemic dengue in Puerto Rico in the 1980's. These data allow us to (1) correlate population genetic changes with cycles of endemic and epidemic transmission; (2) explore the nature of selection acting on different viral gene regions; (3) identify potentially significant amino acid positions and determine their association with disease severity and/or transmission potential; and (4) evaluate the importance of recombination in the evolution of the dengue virus in PR. Our results to date demonstrate that: (1) dengue serotype 4 evolves throughout the Caribbean somewhat independently for a given island, with the occasional infusion of variants from other islands as a function of proximity and other socio-geographic factors (Foster et al., 2003). (2) the history of dengue-4 populations in PR is characterized by striking lineage turnover correlated, driven in part by selection on a nonstructural gene, NS2A (Bennett et al., 2003 ). (3) dengue serotype 2 and 4 indicates are evolving in different ways, the former marked by less lineage turnover, changing evolutionary rates, and more changes in the structural regions (in prep). Future directions include expanding comparative studies between serotypes to include more gene regions and more geographic locations. Improved understanding of the role of viral evolution in disease dynamics will ultimately contribute to the development of evolutionary-based strategies for the control of this infectious disease.
		Dengue 4 (DEN-4) from Puerto Rico maximum likelihood phylogeny based on 3543 base-pair sequences spanning structural genes capsid, membrane, & envelope, and non-structural genes NS1 (3' end only), NS2A & NS4B. Bars across internal branches represent amino acid changes that have occurred during the evolution of DEN-4. Numbers above the bars indicate codonposition within the gene indicated: E for envelope, N1 for NS1, & 2A for NS2A. This work was done in collaboration with the US Centers for Disease Control & Prevention and Oxford University Evolutionary Biology Group, and funded by NIH.
	Scales of connectivity and biodiversity of coral reef fishes

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