The sense of smell in mice involves the detection of odors and pheromones by many hundreds of olfactory and vomeronasal receptors. The genes that encode these receptors account for around 5% of the whole gene catalog, but they are poorly understood because they are very similar to each other, and are thought to be turned on randomly in only a small number of cells. Here we use multiple gene expression technologies to curate and measure the activity of all the genes involved in the detection of odors and find evidence of many new ones. We show that most genes encoding olfactory and vomeronasal receptors have complex, multi-exonic structures that generate different isoforms. We find that some receptors are consistently more abundant in the nose than others, which suggests they are not turned on randomly. This may explain why mice are particularly sensitive to some odors, but less attuned to others. We find that overall males and females differ very little in gene expression, despite having altered behavioral responses to the same odors. Thus diversity in receptor expression can explain differences in odor sensitivity, but does not appear to dictate whether sex pheromones are differentially detected by males or females.
Vyšlo v časopise: The Olfactory Transcriptomes of Mice. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004593 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004593
1. DulacC, TorelloAT (2003) Molecular detection of pheromone signals in mammals: from genes to behaviour. Nat Rev Neurosci 4 : 551–562.
2. ChameroP, MartonTF, LoganDW, FlanaganK, CruzJR, et al. (2007) Identification of protein pheromones that promote aggressive behaviour. Nature 450 : 899–902.
3. RobertsSA, SimpsonDM, ArmstrongSD, DavidsonAJ, RobertsonDH, et al. (2010) Darcin: a male pheromone that stimulates female memory and sexual attraction to an individual male's odour. BMC Biol 8 : 75.
4. HagaS, HattoriT, SatoT, SatoK, MatsudaS, et al. (2010) The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor. Nature 466 : 118–122.
5. PapesF, LoganDW, StowersL (2010) The vomeronasal organ mediates interspecies defensive behaviors through detection of protein pheromone homologs. Cell 141 : 692–703.
6. FerreroDM, MoellerLM, OsakadaT, HorioN, LiQ, et al. (2013) A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system. Nature 502 : 368–371.
7. MombaertsP (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nat Rev Neurosci 5 : 263–278.
8. NiimuraY (2013) Identification of chemosensory receptor genes from vertebrate genomes. Methods Mol Biol 1068 : 95–105.
9. ZhangX, RogersM, TianH, ZouDJ, LiuJ, et al. (2004) High-throughput microarray detection of olfactory receptor gene expression in the mouse. Proc Natl Acad Sci U S A 101 : 14168–14173.
10. PluznickJL, ZouDJ, ZhangX, YanQ, Rodriguez-GilDJ, et al. (2009) Functional expression of the olfactory signaling system in the kidney. Proc Natl Acad Sci U S A 106 : 2059–2064.
11. FukudaN, YomogidaK, OkabeM, TouharaK (2004) Functional characterization of a mouse testicular olfactory receptor and its role in chemosensing and in regulation of sperm motility. J Cell Sci 117 : 5835–5845.
12. SpehrM, GisselmannG, PoplawskiA, RiffellJA, WetzelCH, et al. (2003) Identification of a testicular odorant receptor mediating human sperm chemotaxis. Science 299 : 2054–2058.
13. ZhangX, De la CruzO, PintoJM, NicolaeD, FiresteinS, et al. (2007) Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray. Genome Biol 8: R86.
14. ChessA, SimonI, CedarH, AxelR (1994) Allelic inactivation regulates olfactory receptor gene expression. Cell 78 : 823–834.
15. KhanM, VaesE, MombaertsP (2011) Regulation of the probability of mouse odorant receptor gene choice. Cell 147 : 907–921.
16. KimchiT, XuJ, DulacC (2007) A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 448 : 1009–1014.
17. StowersL, LoganDW (2010) Sexual dimorphism in olfactory signaling. Curr Opin Neurobiol 20 : 770–775.
18. SakuraiT, NakagawaT, MitsunoH, MoriH, EndoY, et al. (2004) Identification and functional characterization of a sex pheromone receptor in the silkmoth Bombyx mori. Proc Natl Acad Sci U S A 101 : 16653–16658.
19. KohlJ, OstrovskyAD, FrechterS, JefferisGS (2013) A bidirectional circuit switch reroutes pheromone signals in male and female brains. Cell 155 : 1610–1623.
20. HerradaG, DulacC (1997) A novel family of putative pheromone receptors in mammals with a topographically organized and sexually dimorphic distribution. Cell 90 : 763–773.
21. CuschieriA, BannisterLH (1974) Some histochemical observations on the mucosubstances of the nasal glands of the mouse. Histochem J 6 : 543–558.
22. Ibarra-SoriaX, LevitinMO, LoganDW (2013) The genomic basis of vomeronasal-mediated behaviour. Mamm Genome 25 : 75–86.
23. KhanM, VaesE, MombaertsP (2013) Temporal patterns of odorant receptor gene expression in adult and aged mice. Mol Cell Neurosci 57 : 120–129.
24. MortazaviA, WilliamsBA, McCueK, SchaefferL, WoldB (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5 : 621–628.
25. HebenstreitD, FangM, GuM, CharoensawanV, van OudenaardenA, et al. (2011) RNA sequencing reveals two major classes of gene expression levels in metazoan cells. Mol Syst Biol 7 : 497.
26. YoungJM, MassaHF, HsuL, TraskBJ (2010) Extreme variability among mammalian V1R gene families. Genome Res 20 : 10–18.
27. YoungJM, TraskBJ (2007) V2R gene families degenerated in primates, dog and cow, but expanded in opossum. Trends Genet 23 : 212–215.
28. StowersL, LoganDW (2010) Olfactory mechanisms of stereotyped behavior: on the scent of specialized circuits. Curr Opin Neurobiol 20 : 274–280.
29. PlessyC, PascarellaG, BertinN, AkalinA, CarrieriC, et al. (2012) Promoter architecture of mouse olfactory receptor genes. Genome Res 22 : 486–497.
30. RobertsA, PimentelH, TrapnellC, PachterL (2011) Identification of novel transcripts in annotated genomes using RNA-Seq. Bioinformatics 27 : 2325–2329.
31. ZhangX, MarcucciF, FiresteinS (2010) High-throughput microarray detection of vomeronasal receptor gene expression in rodents. Front Neurosci 4 : 164.
32. IsogaiY, SiS, Pont-LezicaL, TanT, KapoorV, et al. (2011) Molecular organization of vomeronasal chemoreception. Nature 478 : 241–245.
33. ClowneyEJ, MagklaraA, ColquittBM, PathakN, LaneRP, et al. (2011) High-throughput mapping of the promoters of the mouse olfactory receptor genes reveals a new type of mammalian promoter and provides insight into olfactory receptor gene regulation. Genome Res 21 : 1249–1259.
34. KaurAW, AckelsT, KuoTH, CichyA, DeyS, et al. (2014) Murine pheromone proteins constitute a context-dependent combinatorial code governing multiple social behaviors. Cell 157 : 676–688.
35. WuMV, ManoliDS, FraserEJ, CoatsJK, TollkuhnJ, et al. (2009) Estrogen masculinizes neural pathways and sex-specific behaviors. Cell 139 : 61–72.
36. YuTT, McIntyreJC, BoseSC, HardinD, OwenMC, et al. (2005) Differentially expressed transcripts from phenotypically identified olfactory sensory neurons. J Comp Neurol 483 : 251–262.
37. UtsumiM, OhnoK, KawasakiY, TamuraM, KuboT, et al. (1999) Expression of major urinary protein genes in the nasal glands associated with general olfaction. J Neurobiol 39 : 227–236.
38. PesD, MameliM, AndreiniI, KriegerJ, WeberM, et al. (1998) Cloning and expression of odorant-binding proteins Ia and Ib from mouse nasal tissue. Gene 212 : 49–55.
39. MiyawakiA, MatsushitaF, RyoY, MikoshibaK (1994) Possible pheromone-carrier function of two lipocalin proteins in the vomeronasal organ. EMBO J 13 : 5835–5842.
40. GenterMB, Van VeldhovenPP, JeggaAG, SakthivelB, KongS, et al. (2003) Microarray-based discovery of highly expressed olfactory mucosal genes: potential roles in the various functions of the olfactory system. Physiol Genomics 16 : 67–81.
41. YoungJM, ShykindBM, LaneRP, Tonnes-PriddyL, RossJA, et al. (2003) Odorant receptor expressed sequence tags demonstrate olfactory expression of over 400 genes, extensive alternate splicing and unequal expression levels. Genome Biol 4: R71.
42. MarioniJC, MasonCE, ManeSM, StephensM, GiladY (2008) RNA-seq: an assessment of technical reproducibility and comparison with gene expression arrays. Genome Res 18 : 1509–1517.
43. PluznickJL, ProtzkoRJ, GevorgyanH, PeterlinZ, SiposA, et al. (2013) Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A 110 : 4410–4415.
44. FeldmesserE, OlenderT, KhenM, YanaiI, OphirR, et al. (2006) Widespread ectopic expression of olfactory receptor genes. BMC Genomics 7 : 121.
45. ShykindBM, RohaniSC, O'DonnellS, NemesA, MendelsohnM, et al. (2004) Gene switching and the stability of odorant receptor gene choice. Cell 117 : 801–815.
46. FussSH, ZhuY, MombaertsP (2013) Odorant receptor gene choice and axonal wiring in mice with deletion mutations in the odorant receptor gene SR1. Mol Cell Neurosci 56 : 212–224.
47. DobinA, DavisCA, SchlesingerF, DrenkowJ, ZaleskiC, et al. (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29 : 15–21.
48. HansenKD, IrizarryRA, WuZ (2012) Removing technical variability in RNA-seq data using conditional quantile normalization. Biostatistics 13 : 204–216.
49. ThorvaldsdottirH, RobinsonJT, MesirovJP (2013) Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform 14 : 178–192.
50. DuP, KibbeWA, LinSM (2008) lumi: a pipeline for processing Illumina microarray. Bioinformatics 24 : 1547–1548.
51. BenagliaT, ChauveauD, HunterDR, YoungDS (2009) mixtools: An R Package for Analyzing Finite Mixture Models. Journal of Statistical Software 32 : 1–29.
52. AndersS, HuberW (2010) Differential expression analysis for sequence count data. Genome Biol 11: R106.
53. Huang daW, ShermanBT, LempickiRA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4 : 44–57.
54. McLarenW, PritchardB, RiosD, ChenY, FlicekP, et al. (2010) Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics 26 : 2069–2070.
55. KumarS, NeiM, DudleyJ, TamuraK (2008) MEGA: a biologist-centric software for evolutionary analysis of DNA and protein sequences. Brief Bioinform 9 : 299–306.
56. SaraivaLR, KorschingSI (2007) A novel olfactory receptor gene family in teleost fish. Genome Res 17 : 1448–1457.
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
