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Dynamic evolution of toll-like receptor multigene families in echinoderms.

Buckley KM, Rast JP - Front Immunol (2012)

Bottom Line: Representatives of most of the S. purpuratus TLR subfamilies and homologs of the mccTLR sequences are found in L. variegatus, although the L. variegatus TLR gene family is notably smaller (68 TLR sequences).The phylogeny of these genes within sea urchins highlights lineage-specific expansions at higher resolution than is evident at the phylum level.These analyses identify quickly evolving TLR subfamilies that are likely to have novel immune recognition functions and other, more stable, subfamilies that may function more similarly to those of vertebrates.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Sunnybrook Research Institute, University of Toronto Toronto, ON, Canada.

ABSTRACT
The genome sequence of the purple sea urchin, Strongylocentrotus purpuratus, a large and long-lived invertebrate, provides a new perspective on animal immunity. Analysis of this genome uncovered a highly complex immune system in which the gene families that encode homologs of the pattern recognition receptors that form the core of vertebrate innate immunity are encoded in large multigene families. The sea urchin genome contains 253 Toll-like receptor (TLR) sequences, more than 200 Nod-like receptors and 1095 scavenger receptor cysteine-rich domains, a 10-fold expansion relative to vertebrates. Given their stereotypic protein structure and simple intron-exon architecture, the TLRs are the most tractable of these families for more detailed analysis. A role for these receptors in immune defense is suggested by their similarity to TLRs in other organisms, sequence diversity, and expression in immunologically active tissues, including phagocytes. The complexity of the sea urchin TLR multigene families is largely derived from expansions independent of those in vertebrates and protostomes, although a small family of TLRs with structure similar to that of Drosophila Toll can be traced to an ancient eumetazoan ancestor. Several other echinoderm sequences are now available, including Lytechinus variegatus, as well as partial sequences from two other sea urchin species. Here, we present an analysis of the invertebrate deuterostome TLRs with emphasis on the echinoderms. Representatives of most of the S. purpuratus TLR subfamilies and homologs of the mccTLR sequences are found in L. variegatus, although the L. variegatus TLR gene family is notably smaller (68 TLR sequences). The phylogeny of these genes within sea urchins highlights lineage-specific expansions at higher resolution than is evident at the phylum level. These analyses identify quickly evolving TLR subfamilies that are likely to have novel immune recognition functions and other, more stable, subfamilies that may function more similarly to those of vertebrates.

No MeSH data available.


TLR TIR domains are more conserved than the LRR regions. The diversity of the amino acid sequences for each of the subfamilies that contain more than eight complete sequences was analyzed as a measure of sequence entropy (Durbin et al., 1998). In the graphs shown, the light blue line indicates the average diversity over a sliding window of 10 amino acids, and the black line shows the average diversity of each of the protein domains marked on the x-axis. In each of the subfamilies, the TIR domains exhibit greater conservation than the ectodomains, and there is significant sequence variation within the LRR domains.
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Figure 3: TLR TIR domains are more conserved than the LRR regions. The diversity of the amino acid sequences for each of the subfamilies that contain more than eight complete sequences was analyzed as a measure of sequence entropy (Durbin et al., 1998). In the graphs shown, the light blue line indicates the average diversity over a sliding window of 10 amino acids, and the black line shows the average diversity of each of the protein domains marked on the x-axis. In each of the subfamilies, the TIR domains exhibit greater conservation than the ectodomains, and there is significant sequence variation within the LRR domains.

Mentions: The sea urchin TLR sequences exhibit striking amino acid diversity. There is significant variability within the conserved leucine-rich repeat framework, both with respect to changes in the amino acid sequence and also short indels. To characterize this diversity we analyzed the sequence entropy of each alignment position for the subfamilies that contained eight or more complete sequences excluding pseudogenes (Ia, Ib, Ic, IIa, III, and IV; Figure 3). Sequence entropy is a measure of diversity that is based on the frequency of each amino acid at each position (Durbin et al., 1998). Results indicate that within subfamilies, the TIR domains are much more conserved than the LRR-containing ectodomains. On average, the ectodomain diversity is three times higher than that of the intracellular TIR domain (Figure 3; Table 2). This is consistent with an association between LRR sequence diversity and ligand-binding function. Furthermore, the levels and patterns of diversity vary among the subfamilies. The average diversity of the Ia sequences was over three times that of the Ic sequences, although both groups are composed of a similar numbers of genes (Figure 3). The peak in LRR diversity also varied among subfamilies. In subfamily Ia, the most diverse region of the ectodomains is in LRR16-18, whereas in subfamily IIa, the highest diversity is observed in LRR3 and LRR14. This variation in sequence diversity may reflect differences in ligand-binding mechanisms among the TLR subfamilies.


Dynamic evolution of toll-like receptor multigene families in echinoderms.

Buckley KM, Rast JP - Front Immunol (2012)

TLR TIR domains are more conserved than the LRR regions. The diversity of the amino acid sequences for each of the subfamilies that contain more than eight complete sequences was analyzed as a measure of sequence entropy (Durbin et al., 1998). In the graphs shown, the light blue line indicates the average diversity over a sliding window of 10 amino acids, and the black line shows the average diversity of each of the protein domains marked on the x-axis. In each of the subfamilies, the TIR domains exhibit greater conservation than the ectodomains, and there is significant sequence variation within the LRR domains.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367398&req=5

Figure 3: TLR TIR domains are more conserved than the LRR regions. The diversity of the amino acid sequences for each of the subfamilies that contain more than eight complete sequences was analyzed as a measure of sequence entropy (Durbin et al., 1998). In the graphs shown, the light blue line indicates the average diversity over a sliding window of 10 amino acids, and the black line shows the average diversity of each of the protein domains marked on the x-axis. In each of the subfamilies, the TIR domains exhibit greater conservation than the ectodomains, and there is significant sequence variation within the LRR domains.
Mentions: The sea urchin TLR sequences exhibit striking amino acid diversity. There is significant variability within the conserved leucine-rich repeat framework, both with respect to changes in the amino acid sequence and also short indels. To characterize this diversity we analyzed the sequence entropy of each alignment position for the subfamilies that contained eight or more complete sequences excluding pseudogenes (Ia, Ib, Ic, IIa, III, and IV; Figure 3). Sequence entropy is a measure of diversity that is based on the frequency of each amino acid at each position (Durbin et al., 1998). Results indicate that within subfamilies, the TIR domains are much more conserved than the LRR-containing ectodomains. On average, the ectodomain diversity is three times higher than that of the intracellular TIR domain (Figure 3; Table 2). This is consistent with an association between LRR sequence diversity and ligand-binding function. Furthermore, the levels and patterns of diversity vary among the subfamilies. The average diversity of the Ia sequences was over three times that of the Ic sequences, although both groups are composed of a similar numbers of genes (Figure 3). The peak in LRR diversity also varied among subfamilies. In subfamily Ia, the most diverse region of the ectodomains is in LRR16-18, whereas in subfamily IIa, the highest diversity is observed in LRR3 and LRR14. This variation in sequence diversity may reflect differences in ligand-binding mechanisms among the TLR subfamilies.

Bottom Line: Representatives of most of the S. purpuratus TLR subfamilies and homologs of the mccTLR sequences are found in L. variegatus, although the L. variegatus TLR gene family is notably smaller (68 TLR sequences).The phylogeny of these genes within sea urchins highlights lineage-specific expansions at higher resolution than is evident at the phylum level.These analyses identify quickly evolving TLR subfamilies that are likely to have novel immune recognition functions and other, more stable, subfamilies that may function more similarly to those of vertebrates.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Sunnybrook Research Institute, University of Toronto Toronto, ON, Canada.

ABSTRACT
The genome sequence of the purple sea urchin, Strongylocentrotus purpuratus, a large and long-lived invertebrate, provides a new perspective on animal immunity. Analysis of this genome uncovered a highly complex immune system in which the gene families that encode homologs of the pattern recognition receptors that form the core of vertebrate innate immunity are encoded in large multigene families. The sea urchin genome contains 253 Toll-like receptor (TLR) sequences, more than 200 Nod-like receptors and 1095 scavenger receptor cysteine-rich domains, a 10-fold expansion relative to vertebrates. Given their stereotypic protein structure and simple intron-exon architecture, the TLRs are the most tractable of these families for more detailed analysis. A role for these receptors in immune defense is suggested by their similarity to TLRs in other organisms, sequence diversity, and expression in immunologically active tissues, including phagocytes. The complexity of the sea urchin TLR multigene families is largely derived from expansions independent of those in vertebrates and protostomes, although a small family of TLRs with structure similar to that of Drosophila Toll can be traced to an ancient eumetazoan ancestor. Several other echinoderm sequences are now available, including Lytechinus variegatus, as well as partial sequences from two other sea urchin species. Here, we present an analysis of the invertebrate deuterostome TLRs with emphasis on the echinoderms. Representatives of most of the S. purpuratus TLR subfamilies and homologs of the mccTLR sequences are found in L. variegatus, although the L. variegatus TLR gene family is notably smaller (68 TLR sequences). The phylogeny of these genes within sea urchins highlights lineage-specific expansions at higher resolution than is evident at the phylum level. These analyses identify quickly evolving TLR subfamilies that are likely to have novel immune recognition functions and other, more stable, subfamilies that may function more similarly to those of vertebrates.

No MeSH data available.