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Evolution of mosquito preference for humans linked to an odorant receptor.

McBride CS, Baier F, Omondi AB, Spitzer SA, Lutomiah J, Sang R, Ignell R, Vosshall LB - Nature (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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Tight linkage of Or4 allelic expression and sulcatone sensitivity to preference for humansa, Protein haplotype network showing seven Or4 alleles segregating within the K27 forest (black) and K14 domestic (brown) parent colonies with a related Ae. albopictus gene shown for reference. Allele A is the reference allele tested in Fig 4a-b. b-c, Frequency of Or4 alleles in K14 and K27 parent colonies (n = 34) (b) and human- and guinea pig-preferring F2 hybrids (n = 100) (c). In c, Or4 alleles were inherited at significantly different frequencies by F2s with different host preference (χ2; P = 0.0002). d, Relative frequency of Or4 alleles in human- and guinea pig-preferring F2 hybrids. Data replotted from c. Index equal to the difference in frequency divided by the sum of the frequencies. Index bounds of -1 and 1 indicate the allele was only present in guinea pig or human-preferring F2s, respectively. e, Sulcatone dose-response curves, with mean ± s.e.m at each concentration. PO, paraffin oil. f-g, Summary of responses to 10-4 sulcatone (f) and spontaneous activity (g). Alleles marked with different letters are significantly different (one-way ANOVA P< 0.0001 for both variables followed by Tukey’s test; n = 13 - 17 sensilla/allele). h, Allele-specific expression derived from human- and guinea pig-preferring F2 hybrids. Variation was significant both between F2 groups (two-way ANOVA; P = 0.004), and among alleles (two-way ANOVA; P = 0.005). i, Joint effects of allele-specific ligand-sensitivity and expression on the F2 frequency index. Multiple regression: P = 0.006 for ligand-sensitivity, P = 0.01 for expression, R2 = 0.92.
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Figure 5: Tight linkage of Or4 allelic expression and sulcatone sensitivity to preference for humansa, Protein haplotype network showing seven Or4 alleles segregating within the K27 forest (black) and K14 domestic (brown) parent colonies with a related Ae. albopictus gene shown for reference. Allele A is the reference allele tested in Fig 4a-b. b-c, Frequency of Or4 alleles in K14 and K27 parent colonies (n = 34) (b) and human- and guinea pig-preferring F2 hybrids (n = 100) (c). In c, Or4 alleles were inherited at significantly different frequencies by F2s with different host preference (χ2; P = 0.0002). d, Relative frequency of Or4 alleles in human- and guinea pig-preferring F2 hybrids. Data replotted from c. Index equal to the difference in frequency divided by the sum of the frequencies. Index bounds of -1 and 1 indicate the allele was only present in guinea pig or human-preferring F2s, respectively. e, Sulcatone dose-response curves, with mean ± s.e.m at each concentration. PO, paraffin oil. f-g, Summary of responses to 10-4 sulcatone (f) and spontaneous activity (g). Alleles marked with different letters are significantly different (one-way ANOVA P< 0.0001 for both variables followed by Tukey’s test; n = 13 - 17 sensilla/allele). h, Allele-specific expression derived from human- and guinea pig-preferring F2 hybrids. Variation was significant both between F2 groups (two-way ANOVA; P = 0.004), and among alleles (two-way ANOVA; P = 0.005). i, Joint effects of allele-specific ligand-sensitivity and expression on the F2 frequency index. Multiple regression: P = 0.006 for ligand-sensitivity, P = 0.01 for expression, R2 = 0.92.

Mentions: Evolution of preference for human hosts could occur not only via changes in Or4 expression, but also via changes in the Or4 coding region that affect protein function. Natural variation in chemoreceptor proteins has previously been shown to alter ligand-sensitivity41 and odour perception42. We found extensive variation in Or4, with seven major alleles present in the two parent colonies and F2 hybrids (Fig. 5a-c). The domestic parent, K14, was dominated by the closely related A and B alleles (Fig. 5a-b) and a highly divergent G allele (Fig. 5b). The K27 forest parent, in contrast, harboured 5 distinct alleles at low to moderate frequency (Fig. 5b). RNAseq data from 8 additional colonies suggest that these patterns apply globally. Human-preferring colonies derived from Kenya, Thailand, USA, and West Africa were dominated by Alike alleles, while animal-preferring colonies from Kenya and Uganda were all highly variable (Extended Data Fig. 2). Although all alleles were present in F2 mosquitoes, they were inherited at different frequencies by human- and guinea pig-preferring individuals (Fig. 5c-d). Moreover, F2s tended to carry alleles characteristic of the parent with similar preference (compare Fig. 5b and d), suggesting that some aspect of allele-specific function affects preference.


Evolution of mosquito preference for humans linked to an odorant receptor.

McBride CS, Baier F, Omondi AB, Spitzer SA, Lutomiah J, Sang R, Ignell R, Vosshall LB - Nature (2014)

Tight linkage of Or4 allelic expression and sulcatone sensitivity to preference for humansa, Protein haplotype network showing seven Or4 alleles segregating within the K27 forest (black) and K14 domestic (brown) parent colonies with a related Ae. albopictus gene shown for reference. Allele A is the reference allele tested in Fig 4a-b. b-c, Frequency of Or4 alleles in K14 and K27 parent colonies (n = 34) (b) and human- and guinea pig-preferring F2 hybrids (n = 100) (c). In c, Or4 alleles were inherited at significantly different frequencies by F2s with different host preference (χ2; P = 0.0002). d, Relative frequency of Or4 alleles in human- and guinea pig-preferring F2 hybrids. Data replotted from c. Index equal to the difference in frequency divided by the sum of the frequencies. Index bounds of -1 and 1 indicate the allele was only present in guinea pig or human-preferring F2s, respectively. e, Sulcatone dose-response curves, with mean ± s.e.m at each concentration. PO, paraffin oil. f-g, Summary of responses to 10-4 sulcatone (f) and spontaneous activity (g). Alleles marked with different letters are significantly different (one-way ANOVA P< 0.0001 for both variables followed by Tukey’s test; n = 13 - 17 sensilla/allele). h, Allele-specific expression derived from human- and guinea pig-preferring F2 hybrids. Variation was significant both between F2 groups (two-way ANOVA; P = 0.004), and among alleles (two-way ANOVA; P = 0.005). i, Joint effects of allele-specific ligand-sensitivity and expression on the F2 frequency index. Multiple regression: P = 0.006 for ligand-sensitivity, P = 0.01 for expression, R2 = 0.92.
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Related In: Results  -  Collection

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Figure 5: Tight linkage of Or4 allelic expression and sulcatone sensitivity to preference for humansa, Protein haplotype network showing seven Or4 alleles segregating within the K27 forest (black) and K14 domestic (brown) parent colonies with a related Ae. albopictus gene shown for reference. Allele A is the reference allele tested in Fig 4a-b. b-c, Frequency of Or4 alleles in K14 and K27 parent colonies (n = 34) (b) and human- and guinea pig-preferring F2 hybrids (n = 100) (c). In c, Or4 alleles were inherited at significantly different frequencies by F2s with different host preference (χ2; P = 0.0002). d, Relative frequency of Or4 alleles in human- and guinea pig-preferring F2 hybrids. Data replotted from c. Index equal to the difference in frequency divided by the sum of the frequencies. Index bounds of -1 and 1 indicate the allele was only present in guinea pig or human-preferring F2s, respectively. e, Sulcatone dose-response curves, with mean ± s.e.m at each concentration. PO, paraffin oil. f-g, Summary of responses to 10-4 sulcatone (f) and spontaneous activity (g). Alleles marked with different letters are significantly different (one-way ANOVA P< 0.0001 for both variables followed by Tukey’s test; n = 13 - 17 sensilla/allele). h, Allele-specific expression derived from human- and guinea pig-preferring F2 hybrids. Variation was significant both between F2 groups (two-way ANOVA; P = 0.004), and among alleles (two-way ANOVA; P = 0.005). i, Joint effects of allele-specific ligand-sensitivity and expression on the F2 frequency index. Multiple regression: P = 0.006 for ligand-sensitivity, P = 0.01 for expression, R2 = 0.92.
Mentions: Evolution of preference for human hosts could occur not only via changes in Or4 expression, but also via changes in the Or4 coding region that affect protein function. Natural variation in chemoreceptor proteins has previously been shown to alter ligand-sensitivity41 and odour perception42. We found extensive variation in Or4, with seven major alleles present in the two parent colonies and F2 hybrids (Fig. 5a-c). The domestic parent, K14, was dominated by the closely related A and B alleles (Fig. 5a-b) and a highly divergent G allele (Fig. 5b). The K27 forest parent, in contrast, harboured 5 distinct alleles at low to moderate frequency (Fig. 5b). RNAseq data from 8 additional colonies suggest that these patterns apply globally. Human-preferring colonies derived from Kenya, Thailand, USA, and West Africa were dominated by Alike alleles, while animal-preferring colonies from Kenya and Uganda were all highly variable (Extended Data Fig. 2). Although all alleles were present in F2 mosquitoes, they were inherited at different frequencies by human- and guinea pig-preferring individuals (Fig. 5c-d). Moreover, F2s tended to carry alleles characteristic of the parent with similar preference (compare Fig. 5b and d), suggesting that some aspect of allele-specific function affects preference.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus