A Peptide Signaling System that Rapidly Enforces Paternity in the Aedes aegypti Mosquito

Abstract

SUMMARY Female Aedes aegypti mosquitoes typically mate only once with one male in their lifetime, a behavior known as “monandry” [1]. This single mating event provisions the female with sufficient sperm to fertilize the >500 eggs she will produce during her ~4–6-week lifespan in the laboratory [2]. Successful mating induces lifetime refractoriness to subsequent insemination by other males, enforcing the paternity of the first male [3–5]. Ae. aegypti mate in flight near human hosts [6], and females become refractory to remating within seconds [1, 3, 4], suggesting the existence of a rapid mechanism to prevent female remating. In this study we implicate HP-I, an Aedes- and male-specific peptide transferred to females [7], and its cognate receptor in the female, NPYLR1 [8], in rapid enforcement of paternity. HP-I mutant males were ineffective in enforcing paternity when a second male was given access to the female within 1 hour. NPYLR1 mutant females produced mixed paternity offspring at high frequency, indicating acceptance of multiple mates. Synthetic HP-I injected into wild-type but not NPYLR1 mutant virgins reduced successful matings. Asian tiger mosquito (Ae. albopictus) HP-I peptides potently activated Ae. aegypti NPYLR1. Invasive Ae. albopictus males are known to copulate with and effectively sterilize Ae. aegypti females by causing them to reject future mates [9]. Cross-species transfer of sperm and active seminal fluid proteins including HP-I may contribute to this phenomenon. This signaling system promotes rapid paternity enforcement within Ae. aegypti, but may promote local extinction in areas where they compete with Ae. albopictus.

Omics approaches to study juvenile hormone synthesis

“…Genomics, transcriptomics, proteomics and metabolomics are reshaping the field of JH synthesis research. Functional studies using reverse genetic approaches such as RNA interference (RNAi)[17,53] or generation of knock-down or gain of function mutants using CRISPR-Cas9 technology [78,79] should validate molecules described in in vitro studies or discover new key players in the regulation of CA activity. Post-transcriptional regulation mechanisms including silencing of gene expression by miRNA most likely play important roles in the remarkable ability of the gland to adjust JH synthesis rates to environmental clues such as nutrition and photoperiod (80,81).…”

Reproductive functions and genetic architecture of the seminal fluid and sperm proteomes of the mosquito Aedes aegypti

“…557 We also note that despite our expanded proteomic coverage, several proteins that we 558 anticipated to be identified were absent. The most notable case was Head Peptide-1, a 559 seminal fluid peptide which has been shown to be transferred in the ejaculate [74] and 560 has been reported to induce short term monogamy in the female after mating [15].…”

“…Lastly, transferred as Ae. aegypti [15,16,18]. The primary goals of this study were to comprehensively 496 catalog male proteins transferred to Ae.…”

“…The most direct 726 application of this study will be the identification of modulators of female reproductive 727 behavior. Mosquito SFPs induce behavioral responses that prevent female 728 remating [14,16,17], including short term mating refractory behavior [15]. To date, the 729 molecule(s) responsible for long term refractoriness has yet to be identified.…”

Novel small molecule agonists of anAedes aegyptineuropeptide Y receptor block mosquito biting behavior

“…aegypti mosquitoes. Early work pointed to Head Peptide-I as the relevant peptide signal mediating suppression (Brown et al, 1994), but more recent studies demonstrated that neither Head Peptide-I nor its receptor NPY-like receptor 1 mediate female host-seeking suppression (Duvall et al, 2017).…”