Dual modes of natural selection on upstream open reading frames.

@article{Neafsey2007DualMO,
  title={Dual modes of natural selection on upstream open reading frames.},
  author={Daniel E. Neafsey and James E. Galagan},
  journal={Molecular biology and evolution},
  year={2007},
  volume={24 8},
  pages={
          1744-51
        }
}
Upstream open reading frames (uORFs) are common features of eukaryotic genes, occurring in 10%-25% of 5' leader sequences. Upstream ORFs that have been subjected to experimental analysis have been generally found to decrease translational efficiency of the downstream coding sequence. Previous investigations of uORFs in mammals and yeast have detected uORFs conserved over long evolutionary distances, prompting speculation about the nature and cause of the natural selection underlying such… 
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TLDR
The roles of many uORFs that are identified by genome-level approaches, as have been initiated for Saccharomyces, Aspergillus, and Cryptococcus species, remain to be determined.
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Genome-wide maps of ribosomal occupancy provide insights into adaptive evolution and regulatory roles of uORFs during Drosophila development
TLDR
This work generated genome-wide maps of translational efficiency at the codon level throughout the life cycle of Drosophila melanogaster and found that many uORFs are transcribed or translated in a developmental stage-, sex-, or tissue-specific manner, suggesting that selective transcription or translation of u ORFs could potentially modulate the TE of the downstream CDSs during Drosphila development.
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It is reported that uORFs correlate with significantly reduced protein expression of the downstream ORF, based on analysis of 11,649 matched mRNA and protein measurements from 4 published mammalian studies, and that 5 uORF-altering mutations, detected within genes previously linked to human diseases, dramatically silence expression ofThe downstream protein.
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Determinants of genome-wide distribution and evolution of uORFs in eukaryotes
TLDR
It is demonstrated how positive and purifying selection, coupled with differences in effective population size (Ne) has shaped the contents of uORFs in eukaryotes, and it is suggested that most uORF might play regulatory roles rather than encode functional peptides.
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TLDR
It is reported that ORF36 is robustly translated as a downstream cistron from the ORF35–37 polycistronic transcript in a cap-dependent manner and two short, upstream open reading frames (uORFs) within the 5′ UTR of the poly cistronic mRNA are identified.
Evolution of alternative and constitutive regions of mammalian 5'UTRs
TLDR
The findings on the evolution and selection in alternative and constitutive regions presented here are consistent with the hypothesis that alternative events in 5'UTRs of mammalian genes are likely to contribute to the regulation of translation.
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