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Open Access Highly Accessed Research article

The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns

Jackie Dolan1, Karen Walshe1, Samantha Alsbury2, Karsten Hokamp1, Sean O'Keeffe1, Tatsuya Okafuji1, Suzanne FC Miller1, Guy Tear2 and Kevin J Mitchell1*

Author Affiliations

1 Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland

2 MRC Centre for Developmental Neurobiology, New Hunts House, Guys Campus, King's College London SE1 1UL, UK

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BMC Genomics 2007, 8:320  doi:10.1186/1471-2164-8-320

Published: 14 September 2007

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

    eL
RRs and an
    FN
3 domain, and six genes encoding transmembrane proteins with
    eLR
Rs
    on
ly (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.