McKinney, E. | Search bioRxiv

bioRxiv2022

Oxytocin/vasopressin system of insects influences parental care in males but not females

AO_SCPLOWBSTRACTC_SCPLOWParental care is thought to evolve through modification of behavioral precursors, which predicts that the mechanistic changes occur in the genes underlying those traits. The duplicated gene system of oxytocin/vasopressin has been broadly co-opted across vertebrates to influence parenting, from a pre-duplication ancestral role in water balance. It remains unclear whether co-option of these genes for parenting is limited to vertebrates. Here, we experimentally tested for associations between inotocin gene expression and water balance, parental acceptance of offspring, and active parenting in the subsocial beetle Nicrophorus orbicollis, to test whether a single copy homologue, inotocin, has similarly been co-opted for parental care in a species with elaborate parenting. As expected, inotocin was associated with water balance in both sexes. Inotocin expression increased around sexual maturation in both males and females, although more clearly in males. Finally, we found that expression of inotocin was not associated with acceptance of larvae but was associated with a transition to male but not female parenting. Moreover, level of offspring provisioning behavior and gene expression were positively correlated in males but uncorrelated in females. Our results suggest a broad co-option of this system for parenting that may have existed prior to gene duplication, and that inotocin may be associated with flexibility in parenting behavior. IO_SCPLOWMPACTC_SCPLOW SO_SCPLOWUMMARYC_SCPLOWOxytocin/vasopressin are amongst the most studied neuropeptides in vertebrates, influencing water balance, mating interactions, and most notably, social bonding. This gene pair evolved from a duplication in the vertebrate lineage of an ancestral vasopressin-like gene. Are the multiple social effects in vertebrates due to this duplication, or are social influences also ancestral? Here, we demonstrate that, in a biparental social beetle with a single copy, inotocin is associated with social interactions between fathers and offspring as well as being associated with the ancestral role of water balance in both males and females. In vertebrates, both oxytocin and vasopressin have been shown to impact social interactions in both sexes, although often showing sex-specificity in their action within species. Our results suggest that this system may have been co-opted for parenting prior to gene duplication and may facilitate flexibility in caring behavior.

evolutionary biology↗

bioRxiv2021

The longitudinal dynamics and natural history of clonal haematopoiesis

Human cells acquire somatic mutations throughout life, some of which can drive clonal expansion. Such expansions are frequent in the haematopoietic system of healthy individuals and have been termed clonal haematopoiesis (CH). While CH predisposes to myeloid neoplasia and other diseases, we have limited understanding of how and when CH develops, what factors govern its behaviour, how it interacts with ageing and how these variables relate to malignant progression. Here, we track 697 CH clones from 385 individuals aged 55 or older over a median of 13 years. We find that 92.4% of clones expanded at a stable exponential rate over the study period, with different mutations driving substantially different growth rates, ranging from 5% (DNMT3A, TP53) to over 50%/yr (SRSF2-P95H). Growth rates of clones with the same mutation differed by approximately +/-5%/yr, proportionately impacting "slow" drivers more substantially. By combining our time-series data with phylogenetic analysis of 1,731 whole genome-sequenced haematopoietic colonies from 7 older individuals, we reveal distinct patterns of lifelong clonal behaviour. DNMT3A-mutant clones preferentially expanded early in life and displayed slower growth in old age, in the context of an increasingly competitive oligoclonal landscape. By contrast, splicing gene mutations only drove expansion later in life, while growth of TET2-mutant clones showed minimal age-dependency. Finally, we show that mutations driving faster clonal growth carry a higher risk of malignant progression. Our findings characterise the lifelong natural history of CH and give fundamental insights into the interactions between somatic mutation, ageing and clonal selection.

cancer biology↗