Cited by 189RNA and protein synthesis mechanismsDNA and Nucleic Acid ChemistryChromosomal and Genetic Variations

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Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage

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Beutler, E, Gelbart, T, Han, J H, Koziol, J A, Beutler, B·1989·Proceedings of the National Academy of Sciences

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Abstract

Noting the scarcity of CpG dinucleotide in total genomic DNA derived from higher organisms and the scarcity of TpA dinucleotide in total genomic DNA derived from most life forms, we examined the distribution of these dinucleotides in sequences derived from functionally distinct types of human DNA, including mitochondrial DNA, intergenic DNA, intron DNA, and DNA destined to be represented in the cytoplasm as mRNA, tRNA, or rRNA. While CpG frequency has fallen to its lowest levels in DNA that is transcriptionally silent, TpA is most stringently excluded in DNA destined to be expressed as mRNA in the cytosol. This observation suggests that the selective pressures leading to the removal of CpG and TpA operate at different levels. With respect to TpA, dinucleotide scarcity may reflect a requirement for mRNA stability and may indicate the action of UpA-selective ribonucleases. We propose that, by reason of its instability, UpA must have been very rare in primordial RNA. Therefore, tRNA with the anticodon for this dinucleotide may have failed to evolve, making UpA the primordial doublet "stop" codon. The modern triplet code has faithfully conserved this arrangement in the two universal stop codons, UAA and UAG.

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Authors: Beutler, E., Gelbart, T., Han, J. H., Koziol, J. A., & Beutler, B.
Affiliations: Scripps Clinic (US)
ORCID: Gelbart, T
Koziol, J A
Beutler, B
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1989-01
Volume: 86
Issue: 1
Pages: 192-196
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.86.1.192
PMC: PMC286430
OpenAlex: W1969474212
Cited by: 189
References: 21
Citations by year: 2026: 4 · 2025: 5 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 17 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 7 · 2014: 4 · 2013: 4 · 2012: 4
FWCI: 4.00
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ca045525-02, RR00833)
National Cancer Institute (R01-CA45525)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-36639)
National Center for Research Resources (RR-00833)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords: CpG, DNA methylation, genetic code evolution, unnatural amino acids, UAG, mRNA stability, tRNA anticodon, mitochondrial DNA, transcriptional silencing
MeSH terms: Base Sequence, Chromosomes, Human, DNA, Mitochondrial, Biological Evolution, Genes, Genetic Code, Humans, Information Systems, Methylation, Ribonucleases, RNA, Selection, Genetic, Transcription, Genetic, Protein Biosynthesis, Dinucleoside Phosphates

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Evolution of the genome and the genetic code: selection at the dinucleotide level by methylation and polyribonucleotide cleavage

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