2024-12-12 アリゾナ大学
<関連情報>
- https://news.arizona.edu/news/study-sheds-light-origin-genetic-code
- https://www.pnas.org/doi/10.1073/pnas.2410311121
最後の普遍的共通祖先のタンパク質ドメインにより、遺伝暗号へのアミノ酸の導入順序が解明される Order of amino acid recruitment into the genetic code resolved by last universal common ancestor’s protein domains
Sawsan Wehbi, Andrew Wheeler, Benoit Morel, +3, and Joanna Masel
Proceedings of the National Academy of Sciences Published:December 12, 2024
DOI:https://doi.org/10.1073/pnas.2410311121
Significance
The order in which the amino acids were added to the genetic code was previously inferred from consensus among forty metrics. Many of these reflect abiotic abundance on ancient Earth. However, the abundances that matter are those within primitive cells that already had sophisticated RNA and perhaps peptide metabolism. Here, we directly infer the order of recruitment from the relative ancestral amino acid frequencies of ancient protein sequences. Small size predicts ancient amino acid enrichment better than the previous consensus metric does. We place metal-binding and sulfur-containing amino acids earlier than previously thought, highlighting the importance of metal-dependent catalysis and sulfur metabolism to ancient life. Understanding early life has implications for our search for life elsewhere in the universe.
Abstract
The current “consensus” order in which amino acids were added to the genetic code is based on potentially biased criteria, such as the absence of sulfur-containing amino acids from the Urey–Miller experiment which lacked sulfur. More broadly, abiotic abundance might not reflect biotic abundance in the organisms in which the genetic code evolved. Here, we instead identify which protein domains date to the last universal common ancestor (LUCA) and then infer the order of recruitment from deviations of their ancestrally reconstructed amino acid frequencies from the still-ancient post-LUCA controls. We find that smaller amino acids were added to the code earlier, with no additional predictive power in the previous consensus order. Metal-binding (cysteine and histidine) and sulfur-containing (cysteine and methionine) amino acids were added to the genetic code much earlier than previously thought. Methionine and histidine were added to the code earlier than expected from their molecular weights and glutamine later. Early methionine availability is compatible with inferred early use of S-adenosylmethionine and early histidine with its purine-like structure and the demand for metal binding. Even more ancient protein sequences—those that had already diversified into multiple distinct copies prior to LUCA—have significantly higher frequencies of aromatic amino acids (tryptophan, tyrosine, phenylalanine, and histidine) and lower frequencies of valine and glutamic acid than single-copy LUCA sequences. If at least some of these sequences predate the current code, then their distinct enrichment patterns provide hints about earlier, alternative genetic codes.