Alternative translation start sites are conserved in eukaryotic genomes.
Nucleic Acids Res
; 39(2): 567-77, 2011 Jan.
Article
en En
| MEDLINE
| ID: mdl-20864444
ABSTRACT
Alternative start AUG codons within a single transcript can contribute to diversity of the proteome; however, their functional significance remains controversial. Here, we provide comparative genomics evidence that alternative start codons are under negative selection in vertebrates, insects and yeast. In genes where the annotated start codon (sAUG) resides within the suboptimal nucleotide context, the downstream in-frame AUG codons (dAUG) among the first â¼30 codon sites are significantly more conserved between species than in genes where the sAUG resides within the optimal context. Proteomics data show that this difference is not an annotation artifact and that dAUGs are in fact under selection as alternative start sites. The key optimal, and sometimes suboptimal, context-determining nucleotides of both the sAUG and dAUGs are conserved. Selection for secondary start sites is stronger in genes with the weak primary start site. Genes with multiple conserved start sites are enriched for transcription factors, and tend to have longer 5'UTRs and higher degree of alternative splicing. Together, these results imply that the use of alternative start sites by means of leaky mRNA scanning is a functional mechanism under selection for increased efficiency of translation and/or for translation of different N-terminal protein variants.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Biosíntesis de Proteínas
/
Codón Iniciador
Límite:
Animals
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Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2011
Tipo del documento:
Article
País de afiliación:
Rusia