Gene Coexpression Network Reveals Highly Conserved, Well-Regulated Anti-Ageing Mechanisms in Old Ant Queens

Abstract

Evolutionary theories of ageing predict a reduction in selection efficiency with age, a so-called ‘selection shadow’, due to extrinsic mortality decreasing effective population size with age. Classic symptoms of ageing include a deterioration in transcriptional regulation and protein homeostasis. Understanding how ant queens defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory of ageing. It has often been discussed that the low extrinsic mortality of ant queens, that are generally well protected within the nest by workers and soldiers, should reduce the selection shadow acting on old queens. We tested this by comparing strength of selection acting on genes upregulated in young and old queens of the ant, Cardiocondyla obscurior. In support of a reduced selection shadow, we find old-biased genes to be under strong purifying selection. We also analysed a gene co-expression network (GCN) with the aim to detect signs of ageing in the form of deteriorating regulation and proteostasis. We find no evidence for ageing. In fact, we detect higher connectivity in old queens indicating increased transcriptional regulation with age. Within the GCN, we discover five highly correlated modules that are upregulated with age. These old-biased modules regulate several anti-ageing mechanisms such as maintenance of proteostasis, transcriptional regulation and stress response. We observe stronger purifying selection on central hub genes of these old-biased modules compared to young-biased modules. These results indicate a lack of transcriptional ageing in old C. obscurior queens possibly facilitated by strong selection at old age and well-regulated anti-ageing mechanisms.

Under the shadow: Old-biased genes are subject to weak purifying selection at both the tissue and cell type-specific levels

“…We predict that the evolution of a constant or decreasing mortality curve, or longevity, should lead to increasing purifying selection on late-expressed genes, which should be measurable using standard transcriptome experiments. This has been exactly what Harrison and colleagues have observed: higher protein sequence conservation among old-biased genes in ant queens (Harrison et al, 2021). However, it remains possible that age-related changes in cell type composition (e.g.…”

Late-life fitness gains and reproductive death in Cardiocondyla obscurior ants

“…Strikingly, a comparative transcriptomic study of 8-week young queens with fully mature C. obscurior queens at or close to their peak fecundity (18 weeks old) did not find signs indicative of aging, but in comparison to aged Drosophila flies an opposite regulation of processes (e.g., cellular ketone, carbohydrate, and organic acid metabolic processes) and genes (e.g., ref(2)P , emp , P5cr-2 , CCHa2 , NLaz , Sirt6 ) involved in aging ( von Wyschetzki et al, 2015 ). Furthermore, a gene co-expression network study using the same data showed higher connectivity in middle-aged queens, indicating increased transcriptional regulation with age ( Harrison et al, 2021 ). Together, this suggests that the physiology of queens is maintained until the fitness peak is reached, at which time they undergo physiological deterioration, while still being reproductively active.…”

Complex regulatory role of DNA methylation in caste- and age-specific expression of a termite

“…In M. natalensis , for instance, which is the focus of the current study, sterile workers live only weeks, while kings and queens can live for over 20 years [ 17 ], with the highly fertile queen laying thousands of eggs per day [ 18 ]. Several important genes and pathways have been indicated as important for longevity and fecundity in termites and other eusocial insects, such as the nutrient-sensing pathways Insulin/insulin-like growth factor (IGF-1) signalling (IIS) and target of rapamycin (TOR) [ 16 , 19 , 20 ], telomerase [ 21 ], transposon defence [ 16 , 22 ], oxidative stress [ 16 , 20 , 23 ], DNA damage repair and mitochondrial functions [ 20 , 23 ] Further, recent studies have also presented evidence for the transcriptional regulation of specific gene co-expression modules associated with old but highly fertile queens in ants [ 24 ], bees [ 25 ] and termites [ 20 , 26 , 27 ]. However, the role of DNA methylation in this absence of the longevity–fecundity trade-off in eusocial insects is so far unknown.…”