The Mouse Genome as a Rodent Model in Evolutionary Studies

Jessica Vamathevan, GlaxoSmithKline Research and Development Ltd, Stevenage, UK
Joanna D Holbrook, Singapore Institute for Clinical Sciences, Singapore
Richard D Emes, University of Nottingham, Nottingham, UK

Published online: November 2012

DOI: 10.1002/9780470015902.a0020754.pub2

The recently updated and complete genome of the C57BL/6J mouse strain provides a model mammalian system for genetics, comparative genomics and evolutionary studies. The extensive freely available resources of mouse genetics and breeds and similarity between mouse and much of human biology makes the mouse genome the primary choice to enable discernment of the biological function of human and other mammalian genes. Of huge importance is that along with human, mouse is currently the only mammalian genome to be sequenced to completeness allowing the investigation of lineage specific biology. In particular the mouse genome sequence provides an unrivalled resource for medical bioscience, in encouraging a deeper understanding of the shared mammalian evolutionary history of potential drug targets.

Key Concepts:

  • The availability of high quality genome sequence is the cornerstone of comparative genomics.
  • Although many mammalian genomes have been sequenced with high coverage they are considered ‘drafts’. Only the mouse and human genomes are characterised as ‘complete’ and do not contain gaps in their genome coverage. The comparison of genes and genomes allows the investigation of evolutionary history of species.
  • The availability of multiple animal genomes provides the raw material for the discipline of genome zoology.

Keywords: comparative genomics; positive selection; adaptive evolution; drug discovery

Figure 1. Codons evolving under adaptive evolution in the small inducible cytokine B13 precursor (CXCL13) gene in 15 mammalian species. CXCL13 was identified as having the highest dN/dS between human and mouse 1:1 orthologues (Emes et al., 2003). Genes identified as sharing a 1:1 orthologous relationship with human CXCL13 using Ensembl (www.ensembl.org) were analysed using the sites models M2 and M8 of PAML. (a) The posterior probabilities of codons residing in the dN/dS>1 site class as calculated using the Bayes empirical Bayes method for models M2 and M8 are shown. The 95% posterior probability cut off, above which positive selection is shown as a dashed line. (b) Sites L55, V91 and S99 with a posterior probability of >95% in both M2 and M8 tests of positive selection are mapped to the crystal structure of human interleukin 8 (PDB 1IL8_A, Clore et al., 1990). Species and Ensembl genes tested: Human, ; Chimpanzee, ; Rhesus Macaque, ; Bushbaby, ; Tree shrew, ; Elephant, ; European hedgehog, ; Dog, ; Armadillo, ; Cat, ; Cow, ; Squirrel, ; Microbat, ; Lesser hedgehog, ; Mouse, ; Rat, .
Figure 2. Branch-sites analysis of disparate adaptive evolution of carbonic anhydrase VI in five mammalian species. Orthologous gene accessions NP_ (human), NM_ (mouse) and (dog) and gene predictions from genomic sequences NW_ (chimpanzee) and NW_ (rat) were analysed using the branch-site methods of PAML. The posterior probabilities of codons residing in the dN/dS>1 site class along three foreground branches (mouse, rat and hominid) as calculated using the Bayes empirical Bayes method are shown. Those residues with >95% posterior probability (marked with a dashed line) are considered to be evolving adaptively along the lineage tested. Here we can see that four residues (S89, A110, 111F and 157 K) are evolving adaptively but only along the mouse lineage, and that the gene is evolving under purifying selection along the hominid lineage. For clarity only the first 200 residues of the protein sequence are shown.
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Related Sub-Topics:

Adaptive Evolution | Evolutionary Genomics | Molecular Evolution | Model Organisms and Human Disease | Pharmacogenetics and Pharmacogenomics
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Article Title: The Mouse Genome as a Rodent Model in Evolutionary Studies
 
How to Cite close
Vamathevan, Jessica, Holbrook, Joanna D, and Emes, Richard D(Nov 2012) The Mouse Genome as a Rodent Model in Evolutionary Studies. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020754.pub2]