Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events

Autor: Igor B. Rogozin, Vyacheslav Yurchenko, Eugenia Poliakov, Ishan Ganguly, Frida Belinky
Rok vydání: 2021
Předmět:
0301 basic medicine
short-term evolution
media_common.quotation_subject
Pseudogene
Nonsense
Nonsense mutation
Biology
Article
Catalysis
Conserved sequence
Evolution
Molecular

lcsh:Chemistry
Inorganic Chemistry
Open Reading Frames
03 medical and health sciences
Negative selection
0302 clinical medicine
Bacterial Proteins
Sequence Homology
Nucleic Acid

expression
Point Mutation
population polymorphism
Selection
Genetic

Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Gene
Phylogeny
Spectroscopy
media_common
Genetics
Bacteria
Base Sequence
Models
Genetic

Organic Chemistry
negative selection
General Medicine
Stop codon
Computer Science Applications
030104 developmental biology
Prokaryotic Cells
lcsh:Biology (General)
lcsh:QD1-999
Codon
Nonsense

Codon
Terminator

Rate of evolution
in-fame stop codon
Pseudogenes
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 1876, p 1876 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 4
ISSN: 1422-0067
DOI: 10.3390/ijms22041876
Popis: Nonsense mutations turn a coding (sense) codon into an in-frame stop codon that is assumed to result in a truncated protein product. Thus, nonsense substitutions are the hallmark of pseudogenes and are used to identify them. Here we show that in-frame stop codons within bacterial protein-coding genes are widespread. Their evolutionary conservation suggests that many of them are not pseudogenes, since they maintain dN/dS values (ratios of substitution rates at non-synonymous and synonymous sites) significantly lower than 1 (this is a signature of purifying selection in protein-coding regions). We also found that double substitutions in codons—where an intermediate step is a nonsense substitution—show a higher rate of evolution compared to null models, indicating that a stop codon was introduced and then changed back to sense via positive selection. This further supports the notion that nonsense substitutions in bacteria are relatively common and do not necessarily cause pseudogenization. In-frame stop codons may be an important mechanism of regulation: Such codons are likely to cause a substantial decrease of protein expression levels.
Databáze: OpenAIRE