|Smith, Timothy - Tim|
|Heaton, Michael - Mike|
Submitted to: Plant and Animal Genome Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 10/3/2006
Publication Date: 1/2/2007
Citation: Smith, T.P., Heaton, M.P., Snelling, W.M., Ylinen, L., Keckesova, Z., Webb, B.L., Towers, G.J. 2007. Genome adaptations of a tripartite motif protein for retroviral defense in cattle and sheep [abstract]. Plant and Animal Genome XV Conference. Poster No. P540.
Technical Abstract: Tripartite motif (TRIM) genes encode proteins composed of RING, B-box, and coiled coil motif domains. Primate TRIM5' has been shown to be a primary determinant of retroviral host cell range restriction in primates. TRIM5 restriction was originally thought to be a primate-specific defense mechanism due to the lack of an orthologous activity in rodent cells, but we recently identified a bovine TRIM protein with TRIM5'-like properties. The protein was identified by RT-PCR from a bovine kidney cell line (MDBK) having a retroviral restriction pattern reminiscent of that seen in primate TRIM5' systems. The draft bovine genome sequence revealed that the bovine ortholog lies in a cluster of at least four highly similar TRIM-encoding genes, indicative of gene duplication events. Furthermore, it appears that the gene producing the restriction-active TRIM protein expressed in MDBK cells is extremely variable between individual cattle, with a key 330 bp segment of the protein-coding region displaying 44 polymorphisms identified in a multi-breed panel of 32 animals, of which 42 alter the amino acid sequence. Sequencing an ovine BAC carrying the locus detected at least four similar genes, while the same length segment of the porcine genome contained only a single TRIM gene, suggesting that the gene duplication occurred after divergence of suidae but prior to ruminant speciation. The current results suggest that ruminants may have adopted a dual strategy for defense against retroviral infections, including both gene duplication and hypervariability within genes to increase the range of viruses that can be targeted.