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, 8 (3), 495-506

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


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

Heli Salmela et al. Genome Biol Evol.


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.

Keywords: Apis mellifera; functional divergence; gene expression; protein structure; seasonality; vitellogenin.


F<sc>ig</sc>. 1.—
Fig. 1.—
The domain architecture of Vg and Vg-like proteins in the honey bee. (A) A bar presentation of the full amino acid sequences. The domains N-sheet, α-helical, and vWFD are highlighted, as well as the polyserine linker. The approximate area that carries lipid molecules is indicated as Lipid cavity. (B) Partial homology models of the proteins. The lipids (orange) are captured from the template structure (PDB-ID = 1LSH). The colors in A correspond to the domain colors in B. Most of the gray areas in the lipid cavity and the vWFD are missing in the models (see Materials and Methods).
F<sc>ig</sc>. 2.—
Fig. 2.—
Location of the fixed amino acid differences between Apis mellifera and Apis cerana in Vg-like-A, -B, and -C proteins. The protein models of A. mellifera are shown in light gray. The amino acid residues with fixed changes are shown as sticks colored green in the N-sheet domain, red in the α-helical domain, and black in the remaining area (partial lipid cavity). For clarity, only the single lipid putatively located in the N-sheet domain is shown (orange). Some structural elements with known or putative functional importance have several fixed changes that are encircled: A loop area in the N-sheet (black circle), an area near the putative lipophilic ligand (gray circle in Vg-like-C), and an area in the α-helical domain (red circle in Vg-like-A).
F<sc>ig</sc>. 3.—
Fig. 3.—
The expression of vg and the vg-like-genes in winter bees (W) and summer nurses (S) (mean ± standard error of the mean, N = 30 winter bees from 3 hives and N = 49 summer nurses from 5 hives, with 9–10 individuals per hive). The expression was measured by qPCR and normalized to a reference gene (RP49 or actin). The summer nurses shown here are the same as the Control group in figure 4.
F<sc>ig</sc>. 4.—
Fig. 4.—
The expression of vg and the vg-like genes in summer nurse bees (mean ± standard error of the mean, N = 49, 44, and 49 for Control, Sham, and Paraquat, respectively, with 7–11 individuals from five hives). The three treatment groups were: Control (noninjected), Sham (injected with bee saline), and Paraquat (injected with oxidative poison Paraquat in bee saline). Significant differences are indicated (0.05 is denoted by *; <0.01 is denoted by ***). The expression was measured by qPCR and normalized to a reference gene.

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