A chicken DNA methylation clock for the prediction of broiler health

Abstract

The domestic chicken (Gallus gallus domesticus) is the globally most important source of commercially produced meat. While genetic approaches have played an important role in the development of chicken stocks, little is known about chicken epigenetics. We have systematically analyzed the chicken DNA methylation machinery and DNA methylation landscape. While overall DNA methylation distribution was similar to mammals, sperm DNA appeared hypomethylated, which correlates with the absence of the DNMT3L cofactor in the chicken genome. Additional analysis revealed the presence of low-methylated regions, which are conserved gene regulatory elements that show tissue-specific methylation patterns. We also used whole-genome bisulfite sequencing to generate 56 single-base resolution methylomes from various tissues and developmental time points to establish an LMR-based DNA methylation clock for broiler chicken age prediction. This clock was used to demonstrate epigenetic age acceleration in animals with experimentally induced inflammation. Our study provides detailed insights into the chicken methylome and suggests a novel application of the DNA methylation clock as a marker for livestock health.

A comparative methylome analysis reveals conservation and divergence of DNA methylation patterns and functions in vertebrates

“…The causes of this reduced methylation are currently unknown. DNMT3L is absent in chicken as DNMT3L was gained by gene duplication in the common amniote ancestor and then lost during the evolution of the bird and monotreme lineage, which could contribute to low sperm DNA methylation [ 36 ]. However, the hypermethylation observed in platypus brain (a monotreme species) argues against an impact of the absence of DNMT3L on the methylome of somatic tissues [ 18 ].…”

Development of DNA methylation-based epigenetic age predictors in loblolly pine (Pinus taeda)

“…In one of the first DNA methylation-based age predictors or "epigenetic clocks" developed by Horvath (2013), the methylation status of 353 cytosines predicts human chronological age with an error of ± 3.6 years. Epigenetic clocks have subsequently been developed in a variety of other mammalian (Horvath, 2013;Weidner et al, 2014), avian (Raddatz et al, 2021), and fish species (Anastasiadi & Piferrer, 2020;Bertucci, Mason, Rhodes, & Parrott, 2021;Mayne et al, 2020), and are currently being applied to biomedical and conservation problems, as well to questions regarding their relationship to the underlying biology of aging and senescence (Bertucci & Parrott, 2020;Kabacik, Horvath, Cohen, & Raj, 2018). However, whereas the phenomenon of epigenetic aging appears to be a conserved aspect of biological aging in vertebrates, age-associated changes to DNA methylation and their ability to predict chronological age in plants is relatively unexplored (Parrott & Bertucci, 2019).…”

Development of Epigenetic Clocks for Key Ruminant Species

“…For example, in humans, accelerated epigenetic ageing has been associated with a vast range of disorders from metabolic, infectious, and degenerative disease to frailty, traumatic stress and post-traumatic stress disorder as well as lifestyle factors such as smoking and obesity [ 7 , 8 , 9 ]. These findings proffer the potential to utilize epigenetic clocks as a biomarker for health and age-related degeneration, a tool that could be deployed in the livestock sector to complement the current genetic framework for the selection of traits such as longevity [ 10 ]. More specifically, early selection of animals with a “reduced biological age”, i.e., slower aging, could result in animals with improved longevity.…”