DNA methylation networks underlying mammalian traits.

Area of Science:

• Genomics and Evolutionary Biology
• Epigenetics
• Mammalian Biology

Background:

• Traditional phylogenetics relies on genomic sequences.
• Epigenetic modifications, like DNA methylation, also play a role in biological traits and evolution.
• Understanding the interplay between genome and epigenome evolution is crucial for deciphering mammalian diversity.

Purpose of the Study:

• To construct phyloepigenetic trees using DNA methylation profiles from a large mammalian dataset.
• To identify epigenetic modules associated with specific mammalian traits.
• To investigate the evolutionary relationship between the genome and epigenome in mammals.

Main Methods:

• Utilized DNA methylation profiles (n = 15,456) from 348 mammalian species.
• Constructed phyloepigenetic trees based on methylation data.
• Employed unsupervised clustering to identify distinct cytosine methylation modules.
• Correlated methylation modules with various biological traits and responses to perturbations.

Main Results:

• Phyloepigenetic trees showed strong similarities to traditional phylogenetic trees.
• Identified 55 distinct cytosine methylation modules, with 30 linked to traits like maximum lifespan, adult weight, age, sex, and human mortality risk.
• Maximum lifespan was associated with methylation in HOXL homeobox genes and developmental processes, potentially regulated by pluripotency factors.
• Observed that methylation states respond to environmental and experimental perturbations (e.g., caloric restriction, diet, Yamanaka factors).

Conclusions:

• DNA methylation patterns provide a robust framework for understanding mammalian evolutionary relationships.
• Epigenetic modifications are significantly associated with key mammalian biological characteristics and traits.
• Demonstrated an intertwined evolution of the genome and epigenome, highlighting their co-evolutionary role in shaping mammalian diversity and function.