Functional annotations of three domestic animal genomes provide vital resources for comparative and agricultural research

Colin Kern,Susan Waters,Zhangyuan Pan,Hans H Cheng,Ruidong Xiang,Perot Saelao,Xiaoqin Xu,Ganrea Chanthavixay,Amanda J Chamberlain ,Ian Korf ,C K Tuggle ,Paul Flicek,Michelle M Halstead ,Alison L Van Eenennaam,Ying Wang,Mary E Delany,Juan F Medrano,Pablo J Ross ,Gerald Quon,Catherine W Ernst ,Huaijun Zhou

doi:10.1038/s41467-021-22100-8

Abstract

Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.

Highlights

Gene regulatory elements are central drivers of phenotypic variation and of critical importance towards understanding the genetics of complex traits
Human and mouse catalogs of regulatory elements (REs)[4,5,6,7] have been critical for identifying genetic variants associated with health and disease[8], and the recent completion of ENCODE phase 3 has further highlighted the importance of functional elements on evolutionary biology, human medicine, and genotype-to-phenotype prediction[9,10]
DNase-seq libraries totaling 805,274,643 reads were produced as well as 1,038,779,370 ATACseq reads from pig samples and 1,190,252,653 ATAC-seq reads from 15 cattle samples

Summary

Introduction

Gene regulatory elements are central drivers of phenotypic variation and of critical importance towards understanding the genetics of complex traits. We present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus) Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are conserved. Understanding the genetic basis of economically important complex traits in domestic animals is a primary focus of animal agriculture, as such knowledge provides the essential basis for the continued genetic improvement necessary to meet the projected increased demand using fewer animals These species are important for their contributions to our understanding of evolutionary biology, human developmental biology, disease, and clinically relevant medicine[2]. These analyses are, to our knowledge, the largest reported genome-wide comparison of REs across birds and mammals in terms of the set of tissues and assays used, and provide a vital data resource for the agricultural research community

Methods

Results

Conclusion