Identification of a Genomic Reservoir for New TRIM Genes in Primate Genomes

Kyudong Han,Sara L Sawyer,Dianne I Lou,Michael Worobey

doi:10.1371/journal.pgen.1002388

Kyudong Han, Sara L Sawyer + Show 2 more

Open Access

https://doi.org/10.1371/journal.pgen.1002388

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Journal: PLoS Genetics	Publication Date: Dec 1, 2011
Citations: 174	License type: CC BY 4.0

Affiliation: The University of Texas at Austin

Abstract

Tripartite Motif (TRIM) ubiquitin ligases act in the innate immune response against viruses. One of the best characterized members of this family, TRIM5α, serves as a potent retroviral restriction factor with activity against HIV. Here, we characterize what are likely to be the youngest TRIM genes in the human genome. For instance, we have identified 11 TRIM genes that are specific to humans and African apes (chimpanzees, bonobos, and gorillas) and another 7 that are human-specific. Many of these young genes have never been described, and their identification brings the total number of known human TRIM genes to approximately 100. These genes were acquired through segmental duplications, most of which originated from a single locus on chromosome 11. Another polymorphic duplication of this locus has resulted in these genes being copy number variable within the human population, with a Han Chinese woman identified as having 12 additional copies of these TRIM genes compared to other individuals screened in this study. Recently, this locus was annotated as one of 34 “hotspot” regions that are also copy number variable in the genomes of chimpanzees and rhesus macaques. Most of the young TRIM genes originating from this locus are expressed, spliced, and contain signatures of positive natural selection in regions known to determine virus recognition in TRIM5α. However, we find that they do not restrict the same retroviruses as TRIM5α, consistent with the high degree of divergence observed in the regions that control target specificity. We propose that this recombinationally volatile locus serves as a reservoir from which new TRIM genes arise through segmental duplication, allowing primates to continually acquire new antiviral genes that can be selected to target new and evolving pathogens.

Highlights

The Tripartite Motif (TRIM) protein family constitutes a newly appreciated group of innate immune effectors involved in the response to viral infection [1,2,3]
We have found a cluster of tandemly arranged TRIM genes on chromosome 11 that serves as a ‘‘reservoir’’ from which new TRIM genes constantly arise
We show that this gene cluster is prone to spawning duplications of itself, allowing primate genomes to continually acquire new TRIM gene copies that can presumably be selected to combat present and new pathogens

Summary

Introduction

The TRIM protein family constitutes a newly appreciated group of innate immune effectors involved in the response to viral infection [1,2,3]. TRIM5a assembles into a hexameric lattice on the surface of retroviral cores as they enter the cytoplasm of a newly infected cell [6]. This interaction stimulates premature capsid disassembly [7,8] and the formation of unanchored K63linked polyubiquitin chains that trigger the production of chemokines and cytokines including interferon [4,9]. TRIM25 interacts with the influenza protein NS1 [14,15] and activates the inflammatory response through the production of unanchored K63-linked polyubiquitin chains [16]. Influenza, herpes simplex virus-1, human cytomegalovirus, and adenovirus are all known to encode proteins that interact with, or alter the activity of, human TRIM proteins [15,17,19]

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