A genomic view of the NOD-like receptor family in teleost fish: identification of a novel NLR subfamily in zebrafish

Kerry J Laing,James R Winton,John D Hansen,Maureen K Purcell

doi:10.1186/1471-2148-8-42

Abstract

BackgroundA large multigene family of NOD-like receptor (NLR) molecules have been described in mammals and implicated in immunity and apoptosis. Little information, however, exists concerning this gene family in non-mammalian taxa. This current study, therefore, provides an in-depth investigation of this gene family in lower vertebrates including extensive phylogenetic comparison of zebrafish NLRs with orthologs in tetrapods, and analysis of their tissue-specific expression.ResultsThree distinct NLR subfamilies were identified by mining genome databases of various non-mammalian vertebrates; the first subfamily (NLR-A) resembles mammalian NODs, the second (NLR-B) resembles mammalian NALPs, while the third (NLR-C) appears to be unique to teleost fish. In zebrafish, NLR-A and NLR-B subfamilies contain five and six genes respectively. The third subfamily is large, containing several hundred NLR-C genes, many of which are predicted to encode a C-terminal B30.2 domain. This subfamily most likely evolved from a NOD3-like molecule. Gene predictions for zebrafish NLRs were verified using sequence derived from ESTs or direct sequencing of cDNA. Reverse-transcriptase (RT)-PCR analysis confirmed expression of representative genes from each subfamily in selected tissues.ConclusionOur findings confirm the presence of multiple NLR gene orthologs, which form a large multigene family in teleostei. Although the functional significance of the three major NLR subfamilies is unclear, we speculate that conservation and abundance of NLR molecules in all teleostei genomes, reflects an essential role in cellular control, apoptosis or immunity throughout bony fish.

Highlights

A large multigene family of NOD-like receptor (NLR) molecules have been described in mammals and implicated in immunity and apoptosis
NLRs are recognized by the presence of three specific domains; an effector domain at the N-terminus that is involved in protein:protein interactions, a central NACHT domain and a C-terminal leucine-rich repeat (LRR) domain
Extending the knowledge of NLRs in ectotherms, this study reports an extensive overview of the NLR family in teleost fish, represented using information derived from the zebrafish Danio rerio

Summary

Introduction

A large multigene family of NOD-like receptor (NLR) molecules have been described in mammals and implicated in immunity and apoptosis. A family of molecules with roles in apoptosis and immune regulation has been discovered in mammalian genomes This gene family, is known under several pseudonyms, including the CATERPILLER (CLR), NACHT, NOD-LRR or NOD-like receptor (NLR) family and is comprised of two major subfamilies of NOD and NALP molecules, along with 3 divergent members; IPAF, the MHC class II transactivator (CIITA) and neuronal apoptosis inhibitory protein (NAIP) [1,2]. NLRs are recognized by the presence of three specific domains; an effector domain at the N-terminus that is involved in protein:protein interactions, a central NACHT (or nucleotide binding oligomerization/NOD) domain and a C-terminal leucine-rich repeat (LRR) domain They are, structurally similar to disease resistance (R) proteins found in plants that are well known for their anti-microbial activities [4]. 22 NLRs have been described including 14 NALPs, with a PYRIN effector domain, and 5 NODs whose effector domain is typically a caspase recruitment domain (CARD)

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