Periodic Reporting for period 1 - wildEPIClock (DNA methylation as epigenetic clock of biological age? An experimental test in wild birds)
Reporting period: 2022-02-01 to 2024-01-31
DNA methylation is an epigenetic modification that changes with progressing age and is now recognized as the best biomarker of organismal ageing. The role of DNA methylation scoring is largely growing in epidemiological studies as it predicts remaining lifespan markedly better than chronological age. Identification of factors that contribute to ageing-related methylation has thereby become of importance for understanding healthy ageing. Overall, this action aimed to develop a DNA methylation age score and apply this to understand causes and consequences of individual variation in life-histories of wild jackdaws (Coloeus monedula) using a large existing set of biological samples. Importantly, the species was studied in its natural environment, which in contrast to laboratory studies, allows to interpret the findings in an evolutionarily relevant context. Another goal of the action involved the development of scientific and transferable skills of the researcher. In conclusion, the researcher alongside the host team unravelled the unique methylomes of sex chromosomes and the disproportionate representation of age-related CpG sites on avian sex chromosomes. The exploitable results from this action contribute to a better understanding of ageing epigenetics and offer new avenues for studying epigenetics of ecological and evolutionary processes with avian models.
The researcher and the host team worked towards learning new skills and state-of-the-art techniques to expand knowledge on DNA methylation. Specifically, the action deeply explored the gene dosage compensation in a female heterogametic sex determination system (such as birds, contrary to male heterogametic systems, such as mammals, humans included) by DNA methylation and the distribution of age-related DNA methylation sites across avian genomes. To make sure the pattern held in more than one bird species, the jackdaw data was complemented with data form the zebra finch (Taeniopygia guttata). Practical know-how on techniques for analyzing DNA methylation, like whole genome bisulfite sequencing, has been gained. Participation in sample extraction and shipment to the sequencing facility was also part of the action. This was followed by engaging analytical work, including processing of large datasets using high-performance computing clusters. The creation of a complete pipeline for analyzing DNA methylation data was another significant achievement. As a result, two publications are currently being finalized for submission. The first manuscript shows a notable decrease in DNA methylation with chromosome length. Unique methylomes of sex chromosomes were observed, with higher methylation on the W chromosome compared to all other chromosomes in both species. Additionally, the study revealed elevated methylation on the Z chromosome relative to autosomes in zebra finches. The higher hypomethylation in gene promoters on male Z compared to female Z implies that upregulation on gene-by-gene basis across female Z chromosome is not occurring. The second manuscript focuses on identifying age-related changes in DNA methylation. It reveals disproportionate representation of age-related CpG sites on sex chromosomes in both species. Furthermore, involvement in a review paper on DNA methylation markers of aging in non-model animals was part of the action, resulting in a publication: https://zenodo.org/records/10914373. The fellowship also involved hands-on work with jackdaws in the field, providing valuable insights into the ecological context of the research. Attendance in various courses further enhanced transferable skills, including aspects of academic leadership, PhD supervision, active bystander and media training. Dissemination of research findings to the public and scientific community through educational workshops and conferences was also carried out. Additionally, involvement in supervisory activities and community engagement, such as serving as a postdoc council member, was part of the experience.
During the fellowship, a substantial progress in understanding DNA methylation and its implications has been made with the application of the state-of-the-art techniques, such as whole genome bisulfite sequencing. The obtained results unravel a potential role for DNA methylation in shaping sex-dependent phenotypes, but not in dosage compensation, and underscore the unique ageing patterns on sex chromosomes. This suggests that sex chromosome DNA methylation is important in sex-dependent senescence, a phenomenon observed across multiple taxa, including humans. Overall, the action findings represent significant progress in understanding the role of DNA methylation in regulating gene expression and ageing in avian species. They pave the way for further research by offering baseline knowledge in wild epigenetics and ageing.