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Non-neutral evolution of H3.3-encoding genes occurs without alterations in protein sequence
Brejnev M Muhire1, Matthew A Booker1,2, Michael Y Tolstorukov3,4
1Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Scientific Reports
|June 13, 2019
Summary
The two human histone H3.3 genes, H3F3A and H3F3B, evolved independently. H3F3B likely represents the ancestral gene for broad expression, while H3F3A evolved for specific cellular programs.
Area of Science:
- Genomics
- Evolutionary Biology
- Molecular Biology
Background:
- Histone H3.3 is a crucial variant for development.
- Human cells possess two independent genes for Histone H3.3: H3F3A and H3F3B.
- The evolutionary origins and distinct functions of these two genes are not well understood.
Purpose of the Study:
- To investigate the evolutionary trajectories of H3F3A and H3F3B.
- To understand the functional divergence and adaptation of the two Histone H3.3 genes.
- To elucidate the role of the two-gene arrangement in fine-tuning gene expression.
Main Methods:
- Phylogenetic analysis across 32 metazoan genomes.
- Comparative synteny and gene structure analysis.
- Codon usage bias analysis.
Main Results:
- H3F3A and H3F3B exhibit independent evolutionary paths.
- H3F3B shows conserved features with ancestral H3.3 and canonical H3 genes.
- H3F3A is specific to Sarcopterygii and under strong purifying selection.
- Distinct codon usage patterns suggest differential roles in gene expression: H3F3B for broad expression, H3F3A for proliferation-specific expression.
Conclusions:
- The two-gene system for Histone H3.3 allows for specialized expression patterns.
- H3F3B is likely the ancestral H3.3 gene, adapted for diverse cellular functions.
- H3F3A evolved for a more restricted role in specific cellular programs, particularly proliferation.
- This evolutionary arrangement enables precise regulation of Histone H3.3 levels across different cellular contexts.
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