Molecular pathways to nonbiting mosquitoes.

Mosquitoes are often referred to as the deadliest animals on Earth because of the devastating pathogens they are able to transmit when females bite and then feed on blood from human hosts (male mosquitoes don’t bite). In 2015 alone there were an estimated 212 million cases of malaria, resulting in 429,000 deaths (1). Approximately one-third of Earth’s population is considered at risk for infection by the dengue virus (2). Furthermore, the rapid emergence and global spread of mosquito-borne viruses, such as West Nile, Zika, and chikungunya, are of increasing public health concern (3, 4). Because effective vaccines and drug therapies are not available for the majority of these mosquito-borne pathogens, efforts to reduce disease transmission have traditionally focused on suppressing or eliminating the mosquito vector, usually by reducing larval habitats (source reduction) or applying insecticides. However, the effectiveness of these traditional approaches is limited by the proliferation of man-made habitats (e.g., discarded tires and cisterns), the rapid geographic spread of vector species associated with human commerce and travel, and the evolution of insecticide resistance. Novel approaches to control are desperately needed. Recently, a variety of exciting strategies to disrupt disease transmission have emerged based on geneticmodification of vectors or infection of vectors with bacterial symbionts (5, 6). These strategies seek to either suppress vector populations to sufficiently low numbers that pathogen transmission cannot be sustained (population suppression), or to introduce and spread genetic modifications or bacterial symbiont infections through natural populations so the mosquitoes are incapable of transmitting pathogens (population replacement). Current population replacement strategies focus on preventing the mosquito from transmitting a pathogen once it has already taken a bite and ingested blood. In PNAS, Bradshaw et al. (7) establish the foundation of an intriguing alternative approach based on the potent logic that mosquitoes that don’t bite cannot transmit disease. Nonbiting Mosquitoes Have Evolved from Biting Ancestors Multiple Times in Nature The benefit of blood feeding (biting) by female mosquitoes is obvious; blood provides a rich and abundant nutritional resource that can be allocated to egg production. The costs of blood feeding are less well appreciated, but likely substantial. A blood-feeding (biting) mosquito must allocate sensory and energetic resources to locate a host and then survive while feeding. Additionally, ingesting warm blood elicits a protective heat-shock response in several species of mosquitoes (8), and blood digestion produces toxic by-products that must be sequestered or metabolically processed (9). In fact, three genera of mosquitoes are entirely nonblood feeding (Malaya, Topomyia, and Toxorhynchites), and nonblood-feeding species occur in at least eight additional mosquito genera containing mostly blood-feeding species (10, 11). Thus, nonbloodfeeding (nonbiting) mosquitoes have evolved from biting ancestors multiple times independently in nature. Fig. 1. Experimental approach using artificial selection to determine the gene-expression differences contributing to naturally evolved differences in biting behavior of the pitcher plant mosquito, W. smithii. (A) Cladogram representing evolutionary relationships among populations. (B) Venn diagram representing DGE between FL avid biters vs. FL disinterested biters (DGE artificial selection) and between FL avid biter vs. ME-obligate nonbiter (DGE evolution in nature). See text for details.