The Mouse Genome as a Rodent Model in Evolutionary Studies

Abstract

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., ). 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., ). Species and Ensembl genes tested: Human, ENSG00000156234; Chimpanzee, ENSPTRG00000016197; Rhesus Macaque, ENSMMUG00000023186; Bushbaby, ENSOGAG00000012119; Tree shrew, ENSTBEG00000016283; Elephant, ENSLAFG00000010039; European hedgehog, ENSEEUG00000007201; Dog, ENSCAFG00000008692; Armadillo, ENSDNOG00000012009; Cat, ENSFCAG00000003734; Cow, ENSBTAG00000008479; Squirrel, ENSSTOG00000015287; Microbat, ENSMLUG00000009593; Lesser hedgehog, ENSETEG00000004845; Mouse, ENSMUSG00000023078; Rat, ENSRNOG00000024899.

Figure 2.

Branch‐sites analysis of disparate adaptive evolution of carbonic anhydrase VI in five mammalian species. Orthologous gene accessions NP_001206.2 (human), NM_009802.1 (mouse) and AB080972 (dog) and gene predictions from genomic sequences NW_101542_4 (chimpanzee) and NW_047727_15 (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.

close

References

Burstein ES, Ott TR, Feddock M et al. (2006) Characterization of the Mas‐related gene family: structural and functional conservation of human and rhesus MrgX receptors. British Journal of Pharmacology 147: 73–82.

Carninci P, Kasukawa T, Katayama S et al. (2005) The transcriptional landscape of the mammalian genome. Science 309: 1559–1563.

Chalmel F, Rolland AD, Niederhauser‐Wiederkehr C et al. (2007) The conserved transcriptome in human and rodent male gametogenesis. Proceedings of the National Academy of Sciences of the USA 104: 8346–8351.

Choi SS and Lahn BT (2003) Adaptive evolution of MRG, a neuron‐specific gene family implicated in nociception. Genome Research 13: 2252–2259.

Clark AG, Glanowski S, Nielsen R et al. (2003) Inferring nonneutral evolution from human‐chimp‐mouse orthologous gene trios. Science 302: 1960–1963.

Clore GM, Appella E, Yamada M et al. (1990) Three‐dimensional structure of interleukin 8 in solution. Biochemistry 29: 1689–1696.

Dong X, Han S, Zylka MJ et al. (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 106: 619–632.

Emes RD, Goodstadt L, Winter EE et al. (2003) Comparison of the genomes of human and mouse lays the foundation of genome zoology. Human Molecular Genetics 12: 701–709.

Guigó R, Dermitzakis ET, Agarwal P et al. (2003) Comparison of mouse and human genomes followed by experimental verification yields an estimated 1,019 additional genes. Proceedings of the National Academy of Sciences of the USA 100: 1140–1145.

Keane TM, Goodstadt L, Denecek P et al. (2011) Mouse genomic variation and its effect on phenotypes and gene regulation. Nature 477: 289–294.

Kola I and Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nature Reviews Drug Discovery 3: 711–715.

Le Brigand K, Russell R, Moreilhon C et al. (2006) An open‐access long oligonucleotide microarray resource for analysis of the human and mouse transcriptomes. Nucleic Acids Research 34: e87.

Lein ES, Hawrylycz MJ, Ao N et al. (2007) Genome‐wide atlas of gene expression in the adult mouse brain. Nature 445(7124): 168–176.

Makalowski W and Boguski MS (1998) Evolutionary parameters of the transcribed mammalian genome: an analysis of 2820 orthologous rodent and human sequences. Proceedings of the National Academy of Sciences of the USA 95: 9407–9412.

Modrek B and Lee CJ (2003) Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss. Nature Genetics 34: 177–180.

Pao SY, Lin WL and Hwang MJ (2006) In silico identification and comparative analysis of differentially expressed genes in human and mouse tissues. BMC Genomics 7: 86.

Ponting CP and Lunter G (2006) Signatures of adaptive evolution within human non‐coding sequence. Human Molecular Genetics 15(Special issue 2): R170–R175.

Ramm SA, Oliver PL, Ponting CP, Stockley P and Emes RD (2008) Sexual selection and the adaptive evolution of mammalian ejaculate proteins. Molecular Biology and Evolution 25(1): 207–219.

Vamathevan J, Hasan S, Emes RD et al. (2008) The role of positive selection in determining the molecular cause of species differences in disease. BMC Evolutionary Biology 8: 273.

Yang Z (2006) Neutral and adaptive protein evolution. In: Harvey PH and May RM (eds) Computational Molecular Evolution, pp. 259–292. Oxford: Oxford University Press.

Yoshida I, Sugiura W, Shibata J et al. (2011) Change of positive selection pressure on HIV‐1 envelope gene inferred by early and recent samples. PLoS One 6(4): e18630.

Zhao S, Shetty J, Hou L et al. (2004) Human, mouse, and rat genome large‐scale rearrangements: stability versus speciation. Genome Research 14: 1851–1860.

Zhuo D, Madden R, Elela SA and Chabot B (2007) Modern origin of numerous alternatively spliced human introns from tandem arrays. Proceedings of the National Academy of Sciences of the USA 104: 882–886.

Zylka MJ, Dong X, Southwell AL et al. (2003) Atypical expansion in mice of the sensory neuron‐specific Mrg G protein‐coupled receptor family. Proceedings of the National Academy of Sciences of the USA 100: 10043–10048.

Further Reading

Church DM, Goodstadt L, Hillier LW et al. (2009) Lineage‐specific biology revealed by a finished genome assembly of the mouse. PLoS Biology 7(5): e1000112.

Eppig JT, Bult CJ, Kadin JA et al. (2005) The Mouse Genome Database (MGD): from genes to mice – a community resource for mouse biology. Nucleic Acids Research 33: D471–D475.

Gibbs RA, Weinstock GM, Metzker ML et al. (2004) Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428: 493–521.

Lander ES, Linton LM, Birren B et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860–921.

The Chimpanzee Sequencing and Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437: 69–87.

Waterston RH, Lindblad‐Toh K, Birney E et al. (2002) Initial sequencing and comparative analysis of the mouse genome. Nature 420: 520–562.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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]