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UniProt release 2015_02

Published February 4, 2015


Mosquitoes prefer humans

Blood-feeding is extremely unusual in insects. Among the 1 to 10 million insect species, only some 10,000 feed on blood, and among these, only 100 target humans. Not only is this behavior rare in terms of species, but within one species, it may be gender-specific. However this small proportion of insects have a dramatic impact on human health. Female mosquitoes are major vectors of human diseases, such as malaria, dengue, yellow fever and chikungunya. Mosquito’s preference for humans is a matter of evolution. Aedes aegypti, the main vector of dengue and yellow fevers, actually exists as 2 subspecies, Aedes aegypti aegypti, feeding on human blood, and Aedes aegypti formosa, a generalist, zoophilic mosquito. It is currently thought that Aedes aegypti aegypti originated from a small population of forest-dwelling Aedes aegypti that became isolated in North Africa when a period of severe drought began in the Sahara approximately 4,000 years ago. The mosquito adapted to these harsh conditions, evolved a preference for breeding in artificial water storage containers and specialized in biting humans. This “domestic” form was reintroduced along the coast of East Africa following human movement and trade, and spread across much of the tropical and subtropical world. Today, along the coasts of Kenya, the 2 subspecies coexist, sometimes just a few hundreds of meters apart, domestic Aedes aegypti aegypti found in homes, laying eggs in water stored in containers indoors, and the forest Aedes aegypti formosa avoiding human settlements, laying eggs in tree holes outdoors.

What is the genetic basis underlying the mosquito’s preference for humans? In order to answer this question, Mc Bride et al. established 29 colonies of each Aedes aegypti subspecies. They observed that, contrary to their forest counterparts, domestic females showed a strong preference for human odor as compared to guinea pig, and were also more responsive in assays in which insects were directly exposed to live hosts, i.e. an anaesthetized guinea-pig and a human arm (the owner of which should be congratulated for her commitment). Analysis of gene expression in antennae, the major olfactory organ, in both subspecies revealed almost 1’000 differentially expressed genes and among them, odorant receptors, a family of insect chemosensory receptors, were significantly overrepresented. Odorant receptor 4 (Or4) was of particular interest. It was upregulated in human-preferring mosquitoes, and also the 2nd most highly expressed odorant receptor in the antennae of domestic females. In addition, Or4 exhibited extensive variations that might affect its function. Or4 responds to sulcatone, a volatile odorant produced by a variety of animals and plants, but whose levels in humans are uniquely high. 7 major Or4 alleles have been identified. Alleles A, B, C, F, and G were highly sensitive to sulcatone, whereas D and E were much less sensitive. Interestingly, human-preferring colonies from various African, Asian and American countries were dominated by A-like alleles, whereas animal-preferring colonies were highly variable. This suggests that both Or4 expression levels and ligand-sensitivity play a role in human preference. Surprisingly, sulcatone has been described as a mosquito repellent at certain concentrations. Mc Bride et al. hypothesized that it could be a repellent at high concentrations and an attractant at lower levels.

The important behavioral (r)evolution form the ancestral Aedes aegypti formosa to Aedes aegypti aegypti is unlikely to be due to a single gene, but at least Or4 is one genetic element clearly associated with these changes. The corresponding Or4 UniProtKB entry has been manually annotated and is publicly available as of this release.

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Changes to the controlled vocabulary of human diseases

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  • Amelogenesis imperfecta and gingival fibromatosis syndrome
  • Glycogen storage disease 14
  • Ichthyosis, autosomal recessive, with hypotrichosis
  • Leigh syndrome, X-linked
  • Loeys-Dietz syndrome 2A
  • Loeys-Dietz syndrome 2B
  • Mental retardation, X-linked 59

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