Structural and functional annotation of the porcine immunome
1 USDA-ARS, Beltsville Human Nutrition Research Center, Diet, Genomics, and Immunology Laboratory, Beltsville, MD 20705, USA
2 Informatics Department, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambs CB10 1SA, UK
3 INRA, UMR85 Physiologie de la Reproduction et des Comportements, F-37380, Nouzilly, France
4 National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan
5 USDA ARS BA Animal Parasitic Diseases Laboratory, Beltsville, MD 20705, USA
6 Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
7 Laboratory of Animal Genetics, Breeding, and Reproduction, Huazhong Agricultural University, Wuhan 430070, PR China
8 Department of Animal Science, Iowa State University, Ames, IA 50011, USA
9 Parco Tecnologico Padano, Integrative Biology Unit, via A. Einstein, 26900, Lodi, Italy
10 Institute of Japan Association for Technology in Agriculture, Forestry and Fisheries, 446-1 Ippaizuka, Kamiyokoba, Tsukuba, Ibaraki 305-0854, Japan
11 The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
12 Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA
13 National Bureau of Animal Genetic Resources, P.B. 129, GT Road By-Pass, Karnal 132001, (Haryana), India
14 INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France
15 Current affiliation: EMBL Outstation-Hinxton, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambs CB10 1SD, UK
BMC Genomics 2013, 14:332 doi:10.1186/1471-2164-14-332Published: 15 May 2013
The domestic pig is known as an excellent model for human immunology and the two species share many pathogens. Susceptibility to infectious disease is one of the major constraints on swine performance, yet the structure and function of genes comprising the pig immunome are not well-characterized. The completion of the pig genome provides the opportunity to annotate the pig immunome, and compare and contrast pig and human immune systems.
The Immune Response Annotation Group (IRAG) used computational curation and manual annotation of the swine genome assembly 10.2 (Sscrofa10.2) to refine the currently available automated annotation of 1,369 immunity-related genes through sequence-based comparison to genes in other species. Within these genes, we annotated 3,472 transcripts. Annotation provided evidence for gene expansions in several immune response families, and identified artiodactyl-specific expansions in the cathelicidin and type 1 Interferon families. We found gene duplications for 18 genes, including 13 immune response genes and five non-immune response genes discovered in the annotation process. Manual annotation provided evidence for many new alternative splice variants and 8 gene duplications. Over 1,100 transcripts without porcine sequence evidence were detected using cross-species annotation. We used a functional approach to discover and accurately annotate porcine immune response genes. A co-expression clustering analysis of transcriptomic data from selected experimental infections or immune stimulations of blood, macrophages or lymph nodes identified a large cluster of genes that exhibited a correlated positive response upon infection across multiple pathogens or immune stimuli. Interestingly, this gene cluster (cluster 4) is enriched for known general human immune response genes, yet contains many un-annotated porcine genes. A phylogenetic analysis of the encoded proteins of cluster 4 genes showed that 15% exhibited an accelerated evolution as compared to 4.1% across the entire genome.
This extensive annotation dramatically extends the genome-based knowledge of the molecular genetics and structure of a major portion of the porcine immunome. Our complementary functional approach using co-expression during immune response has provided new putative immune response annotation for over 500 porcine genes. Our phylogenetic analysis of this core immunome cluster confirms rapid evolutionary change in this set of genes, and that, as in other species, such genes are important components of the pig’s adaptation to pathogen challenge over evolutionary time. These comprehensive and integrated analyses increase the value of the porcine genome sequence and provide important tools for global analyses and data-mining of the porcine immune response.