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The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions.

ABSTRACT: Mammalian immune responses to LPS exposure are typified by the robust induction of NF-kappaB and IFN-beta responses largely mediated by TLR4 signal transduction pathways. In contrast to mammals, Tlr4 signal transduction pathways in nontetrapods are not well understood. Comprehensive syntenic and phylogenetic analyses support our hypothesis that zebrafish tlr4a and tlr4b genes are paralogous rather than orthologous to human TLR4. Furthermore, we provide evidence to support our assertion that the in vivo responsiveness of zebrafish to LPS exposure is not mediated by Tlr4a and Tlr4b paralogs because they fail to respond to LPS stimulation in vitro. Zebrafish Tlr4a and Tlr4b paralogs were also unresponsive to heat-killed Escherichia coli and Legionella pneumophila. Using chimeric molecules in which portions of the zebrafish Tlr4 proteins were fused to portions of the mouse TLR4 protein, we show that the lack of responsiveness to LPS was most likely due to the inability of the extracellular portions of zebrafish Tlr4a and Tlr4b to recognize the molecule, rather than to changes in their capacities to transduce signals through their Toll/IL-1 receptor (TIR) domains. Taken together, these findings strongly support the notion that zebrafish tlr4a and tlr4b paralogs have evolved to provide alternative ligand specificities to the Tlr immune defense system in this species. These data demonstrate that intensive examination of gene histories when describing the Tlr proteins of basally diverging vertebrates is required to obtain fuller appreciation of the evolution of their function. These studies provide the first evidence for the functional evolution of a novel Tlr.

SUBMITTER: Sullivan C

PROVIDER: S-EPMC2819326 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions.

Sullivan Con C Charette Jeremy J Catchen Julian J Lage Christopher R CR Giasson Gregory G Postlethwait John H JH Millard Paul J PJ Kim Carol H CH

Journal of immunology (Baltimore, Md. : 1950) 20091007 9

Mammalian immune responses to LPS exposure are typified by the robust induction of NF-kappaB and IFN-beta responses largely mediated by TLR4 signal transduction pathways. In contrast to mammals, Tlr4 signal transduction pathways in nontetrapods are not well understood. Comprehensive syntenic and phylogenetic analyses support our hypothesis that zebrafish tlr4a and tlr4b genes are paralogous rather than orthologous to human TLR4. Furthermore, we provide evidence to support our assertion that the ...[more]

PMID: 19812203

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Project description:UNLABELLED:Marine bacteria in the Roseobacter and SAR11 lineages successfully exploit the ocean habitat, together accounting for ~40% of bacteria in surface waters, yet have divergent life histories that exemplify patch-adapted versus free-living ecological roles. Here, we use a phylogenetic birth-and-death model to understand how genome content supporting different life history strategies evolved in these related alphaproteobacterial taxa, showing that the streamlined genomes of free-living SAR11 were gradually downsized from a common ancestral genome only slightly larger than the extant members (~2,000 genes), while the larger and variably sized genomes of roseobacters evolved along dynamic pathways from a sizeable common ancestor (~8,000 genes). Genome changes in the SAR11 lineage occurred gradually over ~800 million years, whereas Roseobacter genomes underwent more substantial modifications, including major periods of expansion, over ~260 million years. The timing of the first Roseobacter genome expansion was coincident with the predicted radiation of modern marine eukaryotic phytoplankton of sufficient size to create nutrient-enriched microzones and is consistent with present-day ecological associations between these microbial groups. We suggest that diversification of red-lineage phytoplankton is an important driver of divergent life history strategies among the heterotrophic bacterioplankton taxa that dominate the present-day ocean. IMPORTANCE:One-half of global primary production occurs in the oceans, and more than half of this is processed by heterotrophic bacterioplankton through the marine microbial food web. The diversity of life history strategies that characterize different bacterioplankton taxa is an important subject, since the locations and mechanisms whereby bacteria interact with seawater organic matter has effects on microbial growth rates, metabolic pathways, and growth efficiencies, and these in turn affect rates of carbon mineralization to the atmosphere and sequestration into the deep sea. Understanding the evolutionary origins of the ecological strategies that underlie biochemical interactions of bacteria with the ocean system, and which scale up to affect globally important biogeochemical processes, will improve understanding of how microbial diversity is maintained and enable useful predictions about microbial response in the future ocean.

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The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions.

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The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions.

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