DNA methylation and transcriptome analysis reveal epigenomic differences among three macaque species

Area of Science:

• Genomics
• Epigenetics
• Primate Biology

Background:

• Macaques are widely distributed non-human primates with studied evolutionary histories, but their DNA methylomes are largely uncharacterized.
• Epigenetic modifications, like DNA methylation, play crucial roles in development, physiology, behavior, and evolution.
• Understanding epigenetic variations is key to deciphering functional differences among macaque species.

Purpose of the Study:

• To investigate and compare genome-wide DNA methylation patterns across three macaque species: Tibetan macaque (M. thibetana; TM), Chinese rhesus macaque (M. mulatta lasiota; CR), and crab-eating macaque (M. fascicularis; CE).
• To identify differentially methylated regions (DMRs) and differentially expressed genes (DEGs) among these species.
• To explore the relationship between epigenetic variations, genetic alterations, and functional gene expression, particularly in relation to physiological and habitat differences.

Main Methods:

• Whole-genome bisulfite sequencing was performed on peripheral blood samples from TM, CR, and CE macaques.
• Genome-wide methylation site information was compared across the three species to identify DMRs.
• Differentially expressed genes (DEGs) were identified and analyzed in conjunction with DMRs.
• Functional enrichment analyses were conducted on DMR-related genes.

Main Results:

• Significant numbers of DMRs were identified between all pairwise comparisons: 12,128 (CR vs. CE), 59,165 (CR vs. TM), and 39,751 (CE vs. TM).
• Epigenetic and transcriptomic differences were less pronounced between CR and CE compared to TM.
• DMRs showed altered single nucleotide mutation densities, suggesting a link between genomic alterations and methylation patterns.
• DMR-related genes were enriched in pathways crucial for development and neurological functions, including growth hormone, insulin secretion, thyroid hormone synthesis, morphine addiction, and GABAergic synapses.

Conclusions:

• This study provides the first genome-wide comparison of genetic, gene expression, and epigenetic variations across different macaque species.
• Identified epigenetic and transcriptomic differences may underlie variations in physiology and habitat observed among macaque species.
• The findings offer valuable insights for future research on comparative genomics, epigenetics, and evolutionary biology in macaques.