Inferring DNA methylation in non-skeletal tissues of ancient specimens

Area of Science:

• Paleogenomics
• Epigenetics
• Evolutionary Biology

Background:

• DNA methylation patterns are generally conserved across species but vary across tissues.
• Ancient DNA methylation studies typically focus on skeletal system evolution due to sample type (bones, teeth).
• Tissue-specific DNA methylation develops during embryonic development.

Purpose of the Study:

• To investigate if DNA methylation patterns in one tissue can inform about patterns in other tissues of the same individual.
• To develop and validate an algorithm for cross-tissue DNA methylation inference from ancient samples.
• To explore epigenetic changes in ancient human brain tissues.

Main Methods:

• Developed an algorithm to infer DNA methylation patterns in one tissue from another, based on embryonic development principles.
• Trained and validated the algorithm using extant species' methylation data, achieving high precision (up to 0.92).
• Applied the algorithm to archaic human DNA sequences to reconstruct prefrontal cortex neuron DNA methylation.

Main Results:

• Identified over 1,850 differentially methylated positions in archaic human prefrontal cortex neurons.
• These positions are associated with hundreds of genes, many involved in neural functions (e.g., development, structure).
• Discovered six differentially methylated positions within the NBPF gene family, potentially linked to human brain evolution.

Conclusions:

• The developed algorithm enables the study of epigenetic changes in tissues not preserved in the fossil record.
• Provides novel insights into the evolutionary impact of epigenetic modifications on human brain development and function.
• Opens new avenues for paleogenomic research into ancient epigenomes.