Ancient Duplications Have Led to Functional Divergence of Vitellogenin-Like Genes Potentially Involved in Inflammation and Oxidative Stress in Honey Bees

Abstract

Protection against inflammation and oxidative stress is key in slowing down aging processes. The honey bee (Apis mellifera) shows flexible aging patterns linked to the social role of individual bees. One molecular factor associated with honey bee aging regulation is vitellogenin, a lipoglycophosphoprotein with anti-inflammatory and antioxidant properties. Recently, we identified three genes in Hymenopteran genomes arisen from ancient insect vitellogenin duplications, named vg-like-A, -B, and -C. The function of these vitellogenin homologs is unclear. We hypothesize that some of them might share gene- and protein-level similarities and a longevity-supporting role with vitellogenin. Here, we show how the structure and modifications of the vg-like genes and proteins have diverged from vitellogenin. Furthermore, all three vg-like genes show signs of positive selection, but the spatial location of the selected protein sites differ from those found in vitellogenin. We show that all these genes are expressed in both long-lived winter worker bees and in summer nurse bees with intermediate life expectancy, yet only vg-like-A shows elevated expression in winter bees as found in vitellogenin. Finally, we show that vg-like-A responds more strongly than vitellogenin to inflammatory and oxidative conditions in summer nurse bees, and that also vg-like-B responds to oxidative stress. We associate vg-like-A and, to lesser extent, vg-like-B to the antiaging roles of vitellogenin, but that vg-like-C probably is involved in some other function. Our analysis indicates that an ancient duplication event facilitated the adaptive and functional divergence of vitellogenin and its paralogs in the honey bee.

Vitellogenin in inflammation and immunity in social insects

“…Recent evidence suggests that vitellogenin is involved in modulating inflammation also via other than antioxidative means in the honey bee [33,35] . Vitellogenin gene expression is upregulated by wounding injury [35] , and the protein heavily binds to necrotic cells [33] .…”

“…Vitellogenin gene expression is upregulated by wounding injury [35] , and the protein heavily binds to necrotic cells [33] . Furthermore, vitellogenin strongly binds to cell membrane protrusions called blebs that are an early sign of cell death on a damaged cell [33] .…”

“…Our research group has recently established that insects have more than one copy of vitellogenin type of proteins produced by the fat body tissue; see Morandin et al 2014 for Formica ants, and Salmela et al 2016 for the honey bee. Vitellogenin gene duplication has taken place early in insect evolution, and duplication occurred for a second time before the separation of the Hymenopteran species (bees, ants and wasps) [57] .…”

“…Vitellogenin gene duplication has taken place early in insect evolution, and duplication occurred for a second time before the separation of the Hymenopteran species (bees, ants and wasps) [57] . This has resulted in four copies of genes found in Hymenoptera: vitellogenin (the "traditional" vitellogenin studied for decades in the egg-laying species), and its homologs vitellogenin-like-A, vitellogenin-like-B and vitellogenin-like-C, whose expression has been verified in several Formica ant species and in the honey bee this far [35,57] . These genes were identified in 2014 [57] , and are not to be confused with the species-specific duplications of the "traditional" vitellogenin found earlier in some species, such as, the four vitellogenin copies in the ant Solenopsis invicta [20] and the five copies in the mosquito A. aegypti [58] .…”

“…Unlike vitellogenin, the vitellogenin-like proteins are not the constituents of the egg-yolk [59] . Two of the vitellogenin-like proteins, vitellogenin-like-A and -B, share striking similarities with vitellogenin in terms of protein structure [35,57] . Do vitellogenin-like-A and -B have a role in inflammation and aging?…”