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TAD conservation in vertebrate genomes is driven by stabilising selection.
Fabiana Patalano1, Simen Rød Sandve2, Rein Aasland3
1Department of Biosciences, University of Oslo, 0316, Oslo, Norway.
BMC Biology
|August 5, 2025
Summary
Topologically associating domains (TADs) are conserved across species, with stabilizing selection shaping their evolution, particularly for developmental genes. This highlights TADs' crucial role in 3D genome organization and broader organismal functions.
Area of Science:
- Genomics
- Evolutionary Biology
- Molecular Biology
Background:
- Topologically associating domains (TADs) are key structural and gene regulatory units in chromatin.
- TADs are characterized by high intra-domain contact frequency.
- The evolutionary conservation of TADs across species remains an active area of research.
Purpose of the Study:
- To investigate the evolutionary conservation of TADs across 12 vertebrate species.
- To analyze TAD number, borders, and gene positioning.
- To identify evolutionary pressures shaping TADs.
Main Methods:
- Analysis of Hi-C data from 12 vertebrate species.
- Comparative analysis of TAD features (number, borders, gene positioning).
- Modeling TAD evolution using the Ornstein-Uhlenbeck (OU) process.
Main Results:
- TAD features demonstrate significant conservation across species, decreasing with evolutionary distance.
- The Ornstein-Uhlenbeck process revealed strong stabilizing selection on TAD number in most syntenic blocks.
- Selected syntenic blocks were enriched for conserved noncoding elements regulating development (genomic regulatory blocks), but selection also occurred independently of these or non-developmental genes.
Conclusions:
- TAD conservation is substantial, with stabilizing selection as a major driver of 3D genome evolution.
- While selection on TADs is prominent for developmental genes, their importance extends to broader genome and organismal functions.
- Findings enhance understanding of TADs' evolutionary dynamics and functional significance.
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