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The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns.

Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ - BMC Genomics (2007)

Bottom Line: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development.We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. jadolan@tcd.ie

ABSTRACT

Background: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships.

Results: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.

Conclusion: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

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Group-specific patterns of expansion and diversification. The graphs depict three-dimensional histograms showing the number of clusters (on the z axis) having x members in the fly and y members in the mouse. The clusters used for this analysis are listed [see Additional File 6]. Different patterns of expansion (new members in one species of a conserved subfamily) and diversification (novel subfamilies in one species) are observed across the four major groups of eLRR proteins. Graphs were generated with the SPSS program.
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Figure 5: Group-specific patterns of expansion and diversification. The graphs depict three-dimensional histograms showing the number of clusters (on the z axis) having x members in the fly and y members in the mouse. The clusters used for this analysis are listed [see Additional File 6]. Different patterns of expansion (new members in one species of a conserved subfamily) and diversification (novel subfamilies in one species) are observed across the four major groups of eLRR proteins. Graphs were generated with the SPSS program.

Mentions: In order to assess the extent of expansion (new members of existing subfamilies) and diversification (new subfamilies) across different organisms, we analysed the membership of clusters across mouse and fly. For this purpose, we defined clusters in such a way as to distinguish those with species-specific expansion from those with diversification [see Additional File 6]. For each cluster we counted the number of fly and mouse members and then generated histograms of the number of clusters with x fly members and y mouse members (Figure 5). For example, in the LRR_Ig/FN3 group there is one cluster with one fly gene and three mouse genes (Lrigs) and there are six clusters with no fly genes and three mouse genes (Ntrk, Lrrn1–3, Lrrc4, Amigo, FLRT and Lrrc21 groups). These graphs illustrate the different rates of expansion and diversification across these groups.


The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns.

Dolan J, Walshe K, Alsbury S, Hokamp K, O'Keeffe S, Okafuji T, Miller SF, Tear G, Mitchell KJ - BMC Genomics (2007)

Group-specific patterns of expansion and diversification. The graphs depict three-dimensional histograms showing the number of clusters (on the z axis) having x members in the fly and y members in the mouse. The clusters used for this analysis are listed [see Additional File 6]. Different patterns of expansion (new members in one species of a conserved subfamily) and diversification (novel subfamilies in one species) are observed across the four major groups of eLRR proteins. Graphs were generated with the SPSS program.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2235866&req=5

Figure 5: Group-specific patterns of expansion and diversification. The graphs depict three-dimensional histograms showing the number of clusters (on the z axis) having x members in the fly and y members in the mouse. The clusters used for this analysis are listed [see Additional File 6]. Different patterns of expansion (new members in one species of a conserved subfamily) and diversification (novel subfamilies in one species) are observed across the four major groups of eLRR proteins. Graphs were generated with the SPSS program.
Mentions: In order to assess the extent of expansion (new members of existing subfamilies) and diversification (new subfamilies) across different organisms, we analysed the membership of clusters across mouse and fly. For this purpose, we defined clusters in such a way as to distinguish those with species-specific expansion from those with diversification [see Additional File 6]. For each cluster we counted the number of fly and mouse members and then generated histograms of the number of clusters with x fly members and y mouse members (Figure 5). For example, in the LRR_Ig/FN3 group there is one cluster with one fly gene and three mouse genes (Lrigs) and there are six clusters with no fly genes and three mouse genes (Ntrk, Lrrn1–3, Lrrc4, Amigo, FLRT and Lrrc21 groups). These graphs illustrate the different rates of expansion and diversification across these groups.

Bottom Line: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development.We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. jadolan@tcd.ie

ABSTRACT

Background: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships.

Results: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system.

Conclusion: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.

Show MeSH