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  • 1
    Publication Date: 2014-11-14
    Description: Female mosquitoes are major vectors of human disease and the most dangerous are those that preferentially bite humans. A 'domestic' form of the mosquito Aedes aegypti has evolved to specialize in biting humans and is the main worldwide vector of dengue, yellow fever, and chikungunya viruses. The domestic form coexists with an ancestral, 'forest' form that prefers to bite non-human animals and is found along the coast of Kenya. We collected the two forms, established laboratory colonies, and document striking divergence in preference for human versus non-human animal odour. We further show that the evolution of preference for human odour in domestic mosquitoes is tightly linked to increases in the expression and ligand-sensitivity of the odorant receptor AaegOr4, which we found recognizes a compound present at high levels in human odour. Our results provide a rare example of a gene contributing to behavioural evolution and provide insight into how disease-vectoring mosquitoes came to specialize on humans.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286346/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286346/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McBride, Carolyn S -- Baier, Felix -- Omondi, Aman B -- Spitzer, Sarabeth A -- Lutomiah, Joel -- Sang, Rosemary -- Ignell, Rickard -- Vosshall, Leslie B -- 5UL1TR000043/TR/NCATS NIH HHS/ -- HHSN272200900039C/AI/NIAID NIH HHS/ -- HHSN272200900039C/PHS HHS/ -- K99 DC012069/DC/NIDCD NIH HHS/ -- R00 DC012069/DC/NIDCD NIH HHS/ -- UL1 TR000043/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Nov 13;515(7526):222-7. doi: 10.1038/nature13964.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, New York 10065, USA [2] Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA. ; Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, New York 10065, USA. ; Unit of Chemical Ecology, Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Box 102, Sundsvagen 14, 230 53 Alnarp, Sweden. ; Center for Virus Research, Kenya Medical Research Institute, PO Box 54840 - 00200, Off Mbagathi Way, Nairobi, Kenya.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25391959" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/*physiology ; Alleles ; Animals ; Arthropod Antennae/metabolism ; *Biological Evolution ; Female ; Forests ; Gene Expression Profiling ; Host Specificity ; Humans ; Ketones/analysis/metabolism ; Ligands ; Male ; Molecular Sequence Data ; Receptors, Odorant/*metabolism ; Species Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-09-23
    Description: Blood-feeding insects such as mosquitoes are efficient vectors of human infectious diseases because they are strongly attracted by body heat, carbon dioxide and odours produced by their vertebrate hosts. Insect repellents containing DEET (N,N-diethyl-meta-toluamide) are highly effective, but the mechanism by which this chemical wards off biting insects remains controversial despite decades of investigation. DEET seems to act both at close range as a contact chemorepellent, by affecting insect gustatory receptors, and at long range, by affecting the olfactory system. Two opposing mechanisms for the observed behavioural effects of DEET in the gas phase have been proposed: that DEET interferes with the olfactory system to block host odour recognition and that DEET actively repels insects by activating olfactory neurons that elicit avoidance behaviour. Here we show that DEET functions as a modulator of the odour-gated ion channel formed by the insect odorant receptor complex. The functional insect odorant receptor complex consists of a common co-receptor, ORCO (ref. 15) (formerly called OR83B; ref. 16), and one or more variable odorant receptor subunits that confer odour selectivity. DEET acts on this complex to potentiate or inhibit odour-evoked activity or to inhibit odour-evoked suppression of spontaneous activity. This modulation depends on the specific odorant receptor and the concentration and identity of the odour ligand. We identify a single amino-acid polymorphism in the second transmembrane domain of receptor OR59B in a Drosophila melanogaster strain from Brazil that renders OR59B insensitive to inhibition by the odour ligand and modulation by DEET. Our data indicate that natural variation can modify the sensitivity of an odour-specific insect odorant receptor to odour ligands and DEET. Furthermore, they support the hypothesis that DEET acts as a molecular 'confusant' that scrambles the insect odour code, and provide a compelling explanation for the broad-spectrum efficacy of DEET against multiple insect species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203342/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203342/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pellegrino, Maurizio -- Steinbach, Nicole -- Stensmyr, Marcus C -- Hansson, Bill S -- Vosshall, Leslie B -- R01 DC008600/DC/NIDCD NIH HHS/ -- R01 DC008600-02/DC/NIDCD NIH HHS/ -- R01 DC008600-02S1/DC/NIDCD NIH HHS/ -- R01 DC008600-03/DC/NIDCD NIH HHS/ -- R01 DC008600-03S1/DC/NIDCD NIH HHS/ -- R01 DC008600-03S2/DC/NIDCD NIH HHS/ -- R01 DC008600-04/DC/NIDCD NIH HHS/ -- R01 DC008600-05/DC/NIDCD NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Sep 21;478(7370):511-4. doi: 10.1038/nature10438.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurogenetics and Behaviour, The Rockefeller University, 1230 York Avenue, Box 63, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21937991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avoidance Learning/drug effects ; Brazil ; DEET/*pharmacology ; Drosophila Proteins ; Drosophila melanogaster/classification/genetics/metabolism ; Insect Repellents/*pharmacology ; Ligands ; *Odors ; Olfactory Receptor Neurons/drug effects ; Polymorphism, Genetic/genetics ; Protein Structure, Tertiary ; Receptors, Odorant/chemistry/*genetics/*metabolism ; Species Specificity ; Substrate Specificity
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2013-05-31
    Description: Female mosquitoes of some species are generalists and will blood-feed on a variety of vertebrate hosts, whereas others display marked host preference. Anopheles gambiae and Aedes aegypti have evolved a strong preference for humans, making them dangerously efficient vectors of malaria and Dengue haemorrhagic fever. Specific host odours probably drive this strong preference because other attractive cues, including body heat and exhaled carbon dioxide (CO2), are common to all warm-blooded hosts. Insects sense odours via several chemosensory receptor families, including the odorant receptors (ORs), membrane proteins that form heteromeric odour-gated ion channels comprising a variable ligand-selective subunit and an obligate co-receptor called Orco (ref. 6). Here we use zinc-finger nucleases to generate targeted mutations in the orco gene of A. aegypti to examine the contribution of Orco and the odorant receptor pathway to mosquito host selection and sensitivity to the insect repellent DEET (N,N-diethyl-meta-toluamide). orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses. Behaviourally, orco mutant mosquitoes have severely reduced attraction to honey, an odour cue related to floral nectar, and do not respond to human scent in the absence of CO2. However, in the presence of CO2, female orco mutant mosquitoes retain strong attraction to both human and animal hosts, but no longer strongly prefer humans. orco mutant females are attracted to human hosts even in the presence of DEET, but are repelled upon contact, indicating that olfactory- and contact-mediated effects of DEET are mechanistically distinct. We conclude that the odorant receptor pathway is crucial for an anthropophilic vector mosquito to discriminate human from non-human hosts and to be effectively repelled by volatile DEET.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696029/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696029/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DeGennaro, Matthew -- McBride, Carolyn S -- Seeholzer, Laura -- Nakagawa, Takao -- Dennis, Emily J -- Goldman, Chloe -- Jasinskiene, Nijole -- James, Anthony A -- Vosshall, Leslie B -- AI29746/AI/NIAID NIH HHS/ -- DC012069/DC/NIDCD NIH HHS/ -- R01 AI029746/AI/NIAID NIH HHS/ -- R37 AI029746/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 Jun 27;498(7455):487-91. doi: 10.1038/nature12206. Epub 2013 May 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurogenetics and Behavior, and Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23719379" target="_blank"〉PubMed〈/a〉
    Keywords: Aedes/drug effects/*genetics/*physiology ; Amino Acid Sequence ; Animals ; Base Sequence ; DEET/administration & dosage/*pharmacology ; Drug Resistance/drug effects ; Female ; Genes, Insect/*genetics ; Honey ; Host Specificity/drug effects/*genetics ; Humans ; Insect Repellents/administration & dosage/*pharmacology ; Male ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutation/*genetics ; Neurons/cytology/drug effects ; Odors/analysis ; Olfactory Pathways/cytology/drug effects ; Volatilization
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-03-22
    Description: Humans can discriminate several million different colors and almost half a million different tones, but the number of discriminable olfactory stimuli remains unknown. The lay and scientific literature typically claims that humans can discriminate 10,000 odors, but this number has never been empirically validated. We determined the resolution of the human sense of smell by testing the capacity of humans to discriminate odor mixtures with varying numbers of shared components. On the basis of the results of psychophysical testing, we calculated that humans can discriminate at least 1 trillion olfactory stimuli. This is far more than previous estimates of distinguishable olfactory stimuli. It demonstrates that the human olfactory system, with its hundreds of different olfactory receptors, far outperforms the other senses in the number of physically different stimuli it can discriminate.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483192/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483192/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bushdid, C -- Magnasco, M O -- Vosshall, L B -- Keller, A -- UL1 TR000043/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Mar 21;343(6177):1370-2. doi: 10.1126/science.1249168.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Neurogenetics and Behavior, The Rockefeller University, 1230 York Avenue, Box 63, New York, NY 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24653035" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; *Odors ; *Olfactory Perception ; Smell/*physiology ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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