Wing dimorphism in insects is an evolutionarily adaptive trait to maximize insect fitness under various environments, by which the population could be balanced between dispersing and reproduction. Most studies concern the regulatory mechanisms underlying the stimulation of wing morph in aphids, but relatively little research addresses the molecular basis of wing loss. Here, we found that, while developing normally in winged-destined pea aphids, the wing disc in wingless-destined aphids degenerated 30-hr postbirth and that this degeneration was due to autophagy rather than apoptosis. Activation of autophagy in first instar nymphs reduced the proportion of winged aphids, and suppression of autophagy increased the proportion. REPTOR2, associated with TOR signaling pathway, was identified by RNA-seq as a differentially expressed gene between the two morphs with higher expression in the thorax of wingless-destined aphids. Further genetic analysis indicated that REPTOR2 could be a novel gene derived from a gene duplication event that occurred exclusively in pea aphids on autosome A1 but translocated to the sex chromosome. Knockdown of REPTOR2 reduced autophagy in the wing disc and increased the proportion of winged aphids. In agreement with REPTOR’s canonical negative regulatory role of TOR on autophagy, winged-destined aphids had higher TOR expression in the wing disc. Suppression of TOR activated autophagy of the wing disc and decreased the proportion of winged aphids, and vice versa. Co-suppression of TOR and REPTOR2 showed that dsREPTOR2 could mask the positive effect of dsTOR on autophagy, suggesting that REPTOR2 acted as a key regulator downstream of TOR in the signaling pathway. These results revealed that the TOR signaling pathway suppressed autophagic degradation of the wing disc in pea aphids by negatively regulating the expression of REPTOR2.

The genetic variants introduced into the ancestors of modern humans from interbreeding with Neanderthals have been suggested to contribute an unexpected extent to complex human traits. However, testing this hypothesis has been challenging due to the idiosyncratic population genetic properties of introgressed variants. We developed rigorous methods to assess the contribution of introgressed Neanderthal variants to heritable trait variation relative to that of modern human variants. We applied these methods to analyze 235,592 introgressed Neanderthal variants and 96 distinct phenotypes measured in about 300,000 unrelated white British individuals in the UK Biobank. Introgressed Neanderthal variants have a significant contribution to trait variation consistent with the polygenic architecture of complex phenotypes (contributing 0.12% of heritable variation averaged across phenotypes). However, the contribution of introgressed variants tends to be significantly depleted relative to modern human variants matched for allele frequency and linkage disequilibrium (about 59% depletion on average), consistent with purifying selection on introgressed variants. Different from previous studies (McArthur 2021), we find no evidence for elevated heritability across the phenotypes examined. We identified 348 independent significant associations of introgressed Neanderthal variants with 64 phenotypes . Previous work (Skov 2020) has suggested that a majority of such associations are likely driven by statistical association with nearby modern human variants that are the true causal variants. We therefore developed a customized statistical fine-mapping methodology for introgressed variants that led us to identify 112 regions (at a false discovery proportion of 16%) across 47 phenotypes containing 4,303 unique genetic variants where introgressed variants are highly likely to have a phenotypic effect. Examination of these variants reveal their substantial impact on genes that are important for the immune system, development, and metabolism. Our results provide the first rigorous basis for understanding how Neanderthal introgression modulates complex trait variation in present-day humans.