Comparative assessment of the pig, mouse, and human genomes: A structural and functional analysis of genes involved in immunity

Authors: Dawson, Harry

Submitted to: The Minipig in Biomedical Research
Publication Type: Book / Chapter
Publication Acceptance Date: 7/13/2011
Publication Date: 12/2/2011
Citation: Dawson, H.D. 2011. Comparative assessment of the pig, mouse, and human genomes: A structural and functional analysis of genes involved in immunity. In: McAnulty,P.A., Dayan, A., Hastings, K.H., Ganderup, N.-C., editors. The Minipig in Biomedical Research. Boca Raton, FL: CRC Press. p. 321-341.

Interpretive Summary:

Technical Abstract: A detailed analysis was conducted on portions of the porcine, murine, and human genome associated with the immune response. It was found that non-protein coding RNA/DNA that potentially interact and regulate gene expression, nucleotide similarity, isochore type, and the similarity of 5’ and 3’ UTR motifs are better preserved in pigs and humans than in mice. Evaluation of 1:1 orthology of protein-coding genes indicated that the great majority of human genes that were lost through evolution in the mouse were retained in the pig, with chemokines, the IL-10 family, and chitinase family members most conserved. Conversely, very few mouse genes that were lost through evolution in the human were found in the pig. Comparison of expansion or contraction of orthologous gene families indicated that there were far more similar rates and classes of genes in humans and pigs than in mice. The conservation of homology and structural motifs of 1,371 unambiguous orthologs from pig, mice, and humans revealed that the overall mean similarity to human proteins was significantly higher (p < 0.0001) for pigs (78%) compared to mouse (73%). Transcription factors possessed the highest degree of identity among the three species, while chemokines, interferon receptors, and IL-3/colony stimulating factor family members were the most divergent. The highest degree of structural conservation between humans and pigs was among cytokines that bind to the common cytokine receptor gamma chain, and CCR3-binding chemokines. This information supports the view that pigs represent an intermediate species to test concepts and principles discovered in mouse models that may have applicability to humans, especially related to the modeling of immune responses.