Using DNA methylation profiles ( n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

Robust biomarkers of chronological age have been developed in humans and model mammalian species such as rats and mice using DNA methylation data. The concept of these so-called “epigenetic clocks” has emerged from a large body of literature describing the relationship between genome-wide methylation levels and age. Epigenetic clocks exploit this phenomenon and use small panels of differentially methylated cytosine (CpG) sites to make robust predictions of chronological age, independent of tissue type. Here, we present highly accurate livestock epigenetic clocks for which we have used the custom mammalian methylation array “HorvathMammalMethyl40” to construct the first epigenetic clock for domesticated goat (Capra hircus), cattle (Bos taurus), Red (Cervus elaphus) and Wapiti deer (Cervus canadensis) and composite-breed sheep (Ovis aries). Additionally, we have constructed a ‘farm animal clock’ for all species included in the study, which will allow for robust predictions to be extended to various breeds/strains. The farm animal clock shows similarly high accuracy to the individual species’ clocks (r > 0.97), utilizing only 217 CpG sites to estimate age (relative to the maximum lifespan of the species) with a single mathematical model. We hypothesise that the applications of this livestock clock could extend well beyond the scope of chronological age estimates. Many independent studies have demonstrated that a deviation between true age and clock derived molecular age is indicative of past and/or present health (including stress) status. There is, therefore, untapped potential to utilize livestock clocks in breeding programs as a predictor for age-related production traits.

Globally, one of the greatest challenges to agriculture is the requirement for rapid adaptation of animals to environmental perturbation, whether in response to changes in climate, agricultural systems, or biotic stresses. Genetic adaptation, and ultimately evolution of organisms, occurs through the natural selection of advantageous mutations in DNA sequence over time. Environmental challenges from (a)biotic stress, however, require immediate biological responses, which occur through changes in gene expression. Epigenetic modifications to the genome, such as methylation, can affect gene activity without changing the underlying DNA sequence. This is an important mechanism by which gene expression is stably altered for rapid physiological response to environmental stress. Here, we provide a perspective on the use of DNA methylation profiles as a tool for the livestock industry.

Robust biological biomarkers of chronological age have been developed in humans and model mammalian species such as rats and mice using DNA methylation data. The concept of these so-called “epigenetic clocks” has emerged from a large body of literature describing the correlation between genome-wide methylation levels and age. Epigenetic clocks exploit this phenomenon and use small panels of differentially methylated cytosine (CpG) sites to make robust predictions of chronological age, independent of tissue type. Here we present highly accurate livestock epigenetic clocks whereby we have used the custom mammalian methylation array “HorvathMammalMethyl40” ¹ to construct the first epigenetic clock for domesticated goat ( Capra hircus ), cattle ( Bos taurus ), Red ( Cervus elaphus ) and Wapiti deer ( Cervus canadensis ) and composite-breed sheep ( Ovis aries ). Additionally, we have constructed a New Zealand livestock ‘farm animal clock’ for all animals included in the study, which will enable robust predictions to be extended to various breeds. The farm animal clock shows similarly high accuracies to the individual species’ clocks (r>0.97), utilising only 217 CpG sites to estimate age (relative to the maximum lifespan of the species) with a single mathematical model. We envision that the applications of this livestock clock could extend well beyond the scope of chronological age estimates. Many independent studies have demonstrated that a deviation between true age and clock derived molecular age is indicative of past and/or present health (including stress) status. There is, therefore, untapped potential to utilise livestock clocks in breeding programmes as a predictor for age-related, production traits.

Characterizing the locations of genetic regulatory elements is critical for understanding the regulatory mechanisms of complex phenotypic traits related to production traits and health in livestock species. The Ovine Functional Annotation of Animal Genomes (FAANG) Project aims to characterize transcriptional regulatory elements across the sheep genome to facilitate a better understanding of the biological mechanisms influencing phenotypic traits in sheep. Assays including sequencing of messenger RNA (mRNA-seq), cap analysis of gene expression (CAGE), chromatin immunoprecipitation of histones (ChIP-seq), assay for transposase-accessible chromatin (ATAC-seq), whole genome bisulfite sequencing (WGBS) and reduced representation bisulfite sequencing (RRBS) were performed on tissues collected from the Rambouillet ewe used to assemble the reference genome ARS-UI_Ramb_v2.0. Histone modifications were used to define nine chromatin states for tissues across the genome depicting promoters and enhancers (active, poised, and repressed) using ChromHMM. Chromatin states were overlayed with RNA-seq, ATAC-seq and DNA methylation. These data suggest that active promoter and enhancer states reside in open chromatin regions with a greater transcriptional activity and hypomethylated regions than other states. Further, poised and repressed enhancers did not primarily reside in open chromatin and had less transcriptional activity and more hypermethylated sites compared with active states. Collectively these data define transcriptional regulatory regions throughout the ovine genome which provides a valuable resource to better understand regulatory regions in the genome and how these influence economically important traits in sheep and other livestock species.

The proceedings of the 12th World Congress on Genetics Applied to Livestock Production provide you with 816 papers representing the leading research in livestock genetics around the globe. This boo...