• Chlamydomonas chloroplast gene...

Treffer: Chlamydomonas chloroplast genes tolerate compression of the genetic code to just 51 codons.

Title:
Chlamydomonas chloroplast genes tolerate compression of the genetic code to just 51 codons.
Authors:
Mordaka PM; Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, United Kingdom., Clouston K; Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, United Kingdom., Cui J; Department of Structural and Molecular Biology, University College London, London WC1E 6BT, United Kingdom., Holzer A; Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, United Kingdom.; Holzer Scientific Consulting GmbH, Universität des Saarlandes, Saarbrücken 66123, Germany., Jackson HO; Department of Structural and Molecular Biology, University College London, London WC1E 6BT, United Kingdom., Purton S; Department of Structural and Molecular Biology, University College London, London WC1E 6BT, United Kingdom., Smith AG; Department of Plant Sciences, University of Cambridge, Cambridge CB2 3EA, United Kingdom.
Source:
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2026 Jan 13; Vol. 123 (2), pp. e2506263123. Date of Electronic Publication: 2026 Jan 06.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
Imprint Name(s):
Original Publication: Washington, DC : National Academy of Sciences
MeSH Terms:
Genetic Code*/genetics , Chlamydomonas reinhardtii*/genetics , Codon*/genetics , Chloroplasts*/genetics , Genes, Chloroplast*/genetics
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Grant Information:
BB/R01860X/1 UKRI | Biotechnology and Biological Sciences Research Council (BBSRC); BB/W003538/1 UKRI | Biotechnology and Biological Sciences Research Council (BBSRC); RGP0058/2020 Human Frontier Science Program (HFSP); BB/R01860X/1 UKRI | Biotechnology and Biological Sciences Research Council (BBSRC); BB/W003538/1 UKRI | Biotechnology and Biological Sciences Research Council (BBSRC); RGP0058/2020 Human Frontier Science Program (HFSP); OPP1144 Bill & Melinda Gates Foundation
Contributed Indexing:
Keywords: chloroplast genome; codon compression; genetic code; synthetic biology
Substance Nomenclature:
0 (Codon)
Entry Date(s):
Date Created: 20260106 Date Completed: 20260106 Latest Revision: 20260115
Update Code:
20260115
PubMed Central ID:
PMC12799115
DOI:
10.1073/pnas.2506263123
PMID:
41493811
Database:
MEDLINE

Weitere Informationen

Genome scale engineering has enabled codon compression of the universal genetic code to eliminate seven codons in Escherichia coli , but to allow more radical schemes for codon compression and reassignment to be tested at genome scale, while avoiding significant technical challenges, smaller, simpler genetic systems are needed. Here, we report a recoding scheme for the 205 kb Chlamydomonas reinhardtii chloroplast genome, in which two stop codons and one or more of the codons for arginine, glycine, isoleucine, leucine, and serine, all of which have two cognate transfer RNAs (tRNAs), are absent, compressing the genetic code to 51 codons. Several recoding strategies were tested on the essential rpoA gene, encoding a subunit of the chloroplast RNA polymerase. A defined compression scheme, which relied on swapping the target codons with the permitted frequent codons, could replace the native sequence without affecting expression of a reporter protein or strain fitness under standard laboratory conditions. The same strategy was successfully used for codon compression of ycf1 , encoding a subunit of the chloroplast translocon, psaA and psbA , intron-containing highly expressed genes encoding reaction center subunits of both photosystems, and an 8.5 kb operon encoding essential and nonessential genes. Finally, we tested degeneracy of the 51-codon genetic code by exploring the combinatorial design for the large subunit of Rubisco, relying on restoration of photosynthesis in an rbcL mutant strain. More than 70 functional sequences with diverse codons were recovered. For all recoded genes, viable homoplasmic lines were obtained, showing the efficacy of our codon compression scheme.

Competing interests statement:The authors declare no competing interest.