The evolution of vertebrate Toll-like receptors

The evolution of vertebrate Toll-like receptors

May 12, 2005 (received for review March 18, 2005) | Jared C. Roach*, Gustavo Glusman*, Lee Rowen*, Amardeep Kaur*, Maureen K. Purcell†§, Kelly D. Smith*#, Leroy E. Hood*, and Alan Aderem*
The article "The evolution of vertebrate Toll-like receptors" by Roach et al. provides a comprehensive molecular phylogenetic analysis of vertebrate Toll-like receptors (TLRs). TLRs are crucial components of the innate immune system, recognizing pathogen-associated molecular patterns (PAMPs). The study leverages complete sequences from Takifugu (Japanese pufferfish) and draft genomes of various species to identify and analyze TLR genes. Key findings include: 1. **Molecular Phylogeny**: A molecular tree of vertebrate TLRs reveals six major families, each recognizing a specific class of PAMPs. These families are distinct from those in invertebrates and have evolved under strong selective pressure to maintain specific PAMP recognition. 2. **Gene Orthologs**: Most vertebrates have exactly one gene ortholog for each TLR family, except for the TLR1 family, which has more species-specific adaptations. The TLR11 family is represented in humans only by a pseudogene. 3. **Coincidental Evolution**: Little to no coincidental evolution has been observed in TLR evolution, making it a textbook example of multigene family evolution. 4. **Conservation of Synteny**: Syntenic relationships confirm orthologous relationships and help predict the absence of certain genes in genomes. 5. **Invertebrate TLRs**: Invertebrates, including nematodes, flies, and chordates, have different TLR repertoires, suggesting different evolutionary constraints. 6. **Function and Evolution**: TLRs recognize various pathogens, including lipoproteins, double-stranded RNA, lipopolysaccharides, flagellin, and nucleic acids. The evolution of TLRs is driven by strong selective pressure to maintain specific PAMP recognition. 7. **Future Directions**: The study highlights the need for a more comprehensive list of pathogens and their PAMPs to better understand host-TLR coevolution. The article concludes that the coding sequences and signaling pathways of vertebrate TLRs are highly conserved, reflecting evolutionary conservation at multiple levels. Comparative genomic analyses can contribute to systems biology by identifying parts lists for biological systems.The article "The evolution of vertebrate Toll-like receptors" by Roach et al. provides a comprehensive molecular phylogenetic analysis of vertebrate Toll-like receptors (TLRs). TLRs are crucial components of the innate immune system, recognizing pathogen-associated molecular patterns (PAMPs). The study leverages complete sequences from Takifugu (Japanese pufferfish) and draft genomes of various species to identify and analyze TLR genes. Key findings include: 1. **Molecular Phylogeny**: A molecular tree of vertebrate TLRs reveals six major families, each recognizing a specific class of PAMPs. These families are distinct from those in invertebrates and have evolved under strong selective pressure to maintain specific PAMP recognition. 2. **Gene Orthologs**: Most vertebrates have exactly one gene ortholog for each TLR family, except for the TLR1 family, which has more species-specific adaptations. The TLR11 family is represented in humans only by a pseudogene. 3. **Coincidental Evolution**: Little to no coincidental evolution has been observed in TLR evolution, making it a textbook example of multigene family evolution. 4. **Conservation of Synteny**: Syntenic relationships confirm orthologous relationships and help predict the absence of certain genes in genomes. 5. **Invertebrate TLRs**: Invertebrates, including nematodes, flies, and chordates, have different TLR repertoires, suggesting different evolutionary constraints. 6. **Function and Evolution**: TLRs recognize various pathogens, including lipoproteins, double-stranded RNA, lipopolysaccharides, flagellin, and nucleic acids. The evolution of TLRs is driven by strong selective pressure to maintain specific PAMP recognition. 7. **Future Directions**: The study highlights the need for a more comprehensive list of pathogens and their PAMPs to better understand host-TLR coevolution. The article concludes that the coding sequences and signaling pathways of vertebrate TLRs are highly conserved, reflecting evolutionary conservation at multiple levels. Comparative genomic analyses can contribute to systems biology by identifying parts lists for biological systems.
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