Dynamic instability of the major urinary protein gene family revealed by genomic and phenotypic comparisons between C57 and 129 strain mice.

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB101SA, UK.
Genome biology (Impact Factor: 10.47). 02/2008; 9(5):R91. DOI: 10.1186/gb-2008-9-5-r91
Source: PubMed

ABSTRACT The major urinary proteins (MUPs) of Mus musculus domesticus are deposited in urine in large quantities, where they bind and release pheromones and also provide an individual 'recognition signal' via their phenotypic polymorphism. Whilst important information about MUP functionality has been gained in recent years, the gene cluster is poorly studied in terms of structure, genic polymorphism and evolution.
We combine targeted sequencing, manual genome annotation and phylogenetic analysis to compare the Mup clusters of C57BL/6J and 129 strains of mice. We describe organizational heterogeneity within both clusters: a central array of cassettes containing Mup genes highly similar at the protein level, flanked by regions containing Mup genes displaying significantly elevated divergence. Observed genomic rearrangements in all regions have likely been mediated by endogenous retroviral elements. Mup loci with coding sequences that differ between the strains are identified--including a gene/pseudogene pair--suggesting that these inbred lineages exhibit variation that exists in wild populations. We have characterized the distinct MUP profiles in the urine of both strains by mass spectrometry. The total MUP phenotype data is reconciled with our genomic sequence data, matching all proteins identified in urine to annotated genes.
Our observations indicate that the MUP phenotypic polymorphism observed in wild populations results from a combination of Mup gene turnover coupled with currently unidentified mechanisms regulating gene expression patterns. We propose that the structural heterogeneity described within the cluster reflects functional divergence within the Mup gene family.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The vomeronasal organ (VNO) is a sensory organ that is found in most terrestrial vertebrates and that is principally implicated in the detection of pheromones. The VNO contains specialized sensory neurons organized in a pseudostratified neuroepithelium that recognize chemical signals involved in initiating innate behavioral responses. In rodents, the VNO neuroepithelium is segregated into two distinct zones, apical and basal. The molecular mechanisms involved in ligand detection by apical and basal VNO sensory neurons differ extensively. These two VNO subsystems express different subfamilies of vomeronasal receptors and signaling molecules, detect distinct chemosignals, and project to separate regions of the accessory olfactory bulb (AOB). The roles that these olfactory subdivisions play in the control of specific olfactory-mediated behaviors are largely unclear. However, analysis of mutant mouse lines for signal transduction components together with identification of defined chemosensory ligands has revealed a fundamental role of the basal part of the mouse VNO in mediating a wide range of instinctive behaviors, such as aggression, predator avoidance, and sexual attraction. Here we will compare the divergent functions and synergies between the olfactory subsystems and consider new insights in how higher neural circuits are defined for the initiation of instinctive behaviors.
    Frontiers in Neuroanatomy 01/2014; 8:135. DOI:10.3389/fnana.2014.00135 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mouse urine contains highly polymorphic major urinary proteins that have multiple functions in scent communication through their abilities to bind, transport and release hydrophobic volatile pheromones. The mouse genome encodes for about 20 of these proteins and are classified, based on amino acid sequence similarity and tissue expression patterns, as either central or peripheral major urinary proteins. Darcin is a male specific peripheral major urinary protein and is distinctive in its role in inherent female attraction. A comparison of the structure and biophysical properties of darcin with MUP11, which belongs to the central class, highlights similarity in the overall structure between the two proteins. The thermodynamic stability, however, differs between the two proteins, with darcin being much more stable. Furthermore, the affinity of a small pheromone mimetic is higher for darcin, although darcin is more discriminatory, being unable to bind bulkier ligands. These attributes are due to the hydrophobic ligand binding cavity of darcin being smaller, caused by the presence of larger amino acid side chains. Thus, the physical and chemical characteristics of the binding cavity, together with its extreme stability, are consistent with darcin being able to exert its function after release into the environment.
    PLoS ONE 10/2014; 9(10):e108415. DOI:10.1371/journal.pone.0108415 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Proteins and peptides are used as pheromones by many invertebrates and vertebrates, on land as well as underwater. These molecules are used as pheromones by aquatic animals such as squid, sea hares, and newts. Males in some terrestrial salamander species use high molecular weight glycopeptide pheromones transferred directly to the nostrils of the female. In Drosophila fruit flies, sex peptides in the male's seminal fluid change the female's behaviour so that after mating she rejects other males and starts to lay eggs. The rapid evolution of Drosophila sex peptides and salamander peptide pheromones suggests that sexual conflict may be involved. In mice, exocrine gland-secreting peptide 1 (ESP1) secreted from the male's tear glands is transferred to the female's nose through physical contact during investigation of the facial areas during courtship. ESP1 activates a narrowly specific vomeronasal receptor, leading to receptive behaviour in the female. The urine marks of male territorial house mice contain high concentrations of highly variable major urinary proteins (MUPs). The MUPs bind small molecule pheromones and other odorants, slowly releasing them and thus greatly prolonging the attractive volatile lifetime of the signal. One of the MUPs, darcin, is the same in all male house mice: it is a pheromone in itself. When the female comes into contact with darcin in a scent mark it prompts a learned attraction to both the male's individual chemical signature mixture and the location of the scent mark. Proteins and peptides may also contribute to the highly variable chemical profiles that differ between individual mammals, for example, and that are used as cues to allow individuals to be distinguished.
    Animal Behaviour 09/2014; 97. DOI:10.1016/j.anbehav.2014.07.025 · 3.07 Impact Factor

Full-text (2 Sources)

Available from
May 29, 2014