Kyudong Han#¤, Dianne I. Lou#, Sara L. Sawyer*
Section of Molecular Genetics and Microbiology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America
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.
A fundamental question in biology is how the immune system is able to inactivate the enormous number of pathogens that it faces. The vast majority of pathogens are quickly neutralized by the innate immune system, a large network of defenses to which approximately 1/30 of the human genome is devoted. Because pathogens are always evolving, these innate immunity genes must be able to acquire new specificities. Here we illustrate a novel mechanism of evolution that has been employed by the large family of TRIM innate immunity genes. 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.
Citation: Han K, Lou DI, Sawyer SL (2011) Identification of a Genomic Reservoir for New TRIM Genes in Primate Genomes. PLoS Genet 7(12): e1002388. doi:10.1371/journal.pgen.1002388
Editor: Michael Worobey, University of Arizona, United States of America
Received: August 4, 2011; Accepted: September 29, 2011; Published: December 1, 2011
Copyright: ⓒ 2011 Han et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grants (to SLS) R01-GM-093086 from the National Institutes of Health and 107447-45-RGNT from amfAR, The Foundation for AIDS Research. SLS holds a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund and is an Alfred P. Sloan Research Fellow in Computational and Evolutionary Molecular Biology. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
# These authors contributed equally to this work.
¤ Current address: Department of Nanobiomedical Science, WCU Research Center, Dankook University, Cheonan, Republic of Korea