Primate protein-ligand interfaces exhibit significant conservation and unveil human-specific evolutionary drivers.
Sean B King1,2, Mona Singh2,3
1Department of Molecular Biology, Princeton University, Princeton, New Jersey, United States of America.
Plos Computational Biology
|March 23, 2023
Summary
Protein interaction sites are highly conserved across primates, especially those binding DNA and RNA. Variations in these sites, particularly in gene regulation, may drive primate phenotypic differences.
Area of Science:
- Evolutionary biology
- Genomics
- Biochemistry
Background:
- Primate species exhibit significant phenotypic diversity despite conserved protein sequences.
- Protein functions rely on interactions with other molecules, making interaction sites crucial for function.
Purpose of the Study:
- To investigate the evolutionary patterns of protein-ligand binding sites across 18 primate species.
- To determine if alterations in these interaction sites contribute to primate phenotypic differences.
Main Methods:
- Constructed a dataset of ~4,200 orthologous sequence groups and ~68,000 ligand-binding sites.
- Analyzed patterns of conservation and variation in amino acid residues within these sites across primate phylogeny.
Main Results:
- Protein-ligand interaction sites are significantly more conserved than other protein regions.
- DNA and RNA binding sites show the lowest variation.
- Varying ligand-binding sites are enriched in gene regulatory pathways, with human-specific changes in transcription factors.
Conclusions:
- Ligand-binding sites are under selective pressure in primates.
- Variation in these sites, especially those affecting gene regulation, likely plays a significant role in primate phenotypic evolution.
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