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Molecular Complexity Constrained Early Amino Acid Recruitment into the Genetic Code.
Syeda Ameena Hashmi1, Hamed Chok1, Ricardo Cabrera2
1Blue Marble Space Institute of Science, Seattle, WA 98104, USA.
Genome Biology and Evolution
|January 20, 2026
Summary
This study reveals molecular complexity as a key factor in the genetic code's evolution, showing simple amino acids were incorporated first. This complexity influenced early protein evolution and genetic pathways.
Area of Science:
- Biochemistry
- Evolutionary Biology
- Astrobiology
Background:
- Existing genetic code chronologies often rely on external factors like synthesis experiments or genomic data.
- The influence of intrinsic molecular properties on amino acid recruitment is not well understood.
Purpose of the Study:
- To reconstruct an amino acid chronology based on intrinsic molecular complexity.
- To investigate the role of molecular complexity in shaping the genetic code's evolution.
- To explore universal principles in biochemical evolution.
Main Methods:
- Integrated sixteen molecular complexity metrics from chemical graph and information theory.
- Constructed a minimum spanning tree to represent complexity-based relationships between amino acids.
- Analyzed mutational connectivity and correlation with the Last Universal Common Ancestor's (LUCA) proteome.
Main Results:
- A complexity-based hierarchy emerged, with simple amino acids preceding complex ones, aligning with other chronologies.
- Amino acids with similar complexity showed higher mutational connectivity.
- Molecular complexity correlated with amino acid enrichment in LUCA's inferred proteome.
Conclusions:
- Intrinsic molecular properties, specifically complexity, played a fundamental role in shaping the genetic code.
- The genetic code evolved to balance stability with complexity-preserving substitutions.
- Molecular complexity offers a universal principle for understanding early protein evolution.
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