ArticlePLoS genetics2005
Oscillating evolution of a mammalian locus with overlapping reading frames: an XLalphas/ALEX relay.
Article in PLoS genetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Alternative Reading Frames are an Underappreciated Source of Protein Sequence Novelty.Journal of molecular evolution · 2023Review
- The Lost and Found: Unraveling the Functions of Orphan Genes.Journal of developmental biology · 2023Review
- Stepwise Evolution and Exceptional Conservation of ORF1a/b Overlap in Coronaviruses.Molecular biology and evolution · 2021Article
- Understanding small ORF diversity through a comprehensive transcription feature classification.DNA research : an international journal for rapid publication of reports on genes and genomes · 2021Review
- Stepwise evolution and exceptional conservation of ORF1a/b overlap in coronaviruses.bioRxiv : the preprint server for biology · 2021Article
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- Article
- New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Review
- A simple method for estimating the strength of natural selection on overlapping genes.Genome biology and evolution · 2014Article
- Phylogenetic patterns of emergence of new genes support a model of frequent de novo evolution.BMC genomics · 2013Article
- GeneTack database: genes with frameshifts in prokaryotic genomes and eukaryotic mRNA sequences.Nucleic acids research · 2013Article
- Evolution of viral proteins originated de novo by overprinting.Molecular biology and evolution · 2012Article
- Observation of dually decoded regions of the human genome using ribosome profiling data.Genome research · 2012Article
- Is there a twelfth protein-coding gene in the genome of influenza A? A selection-based approach to the detection of overlapping genes in closely related sequences.Journal of molecular evolution · 2011Article
- The evolutionary origin of orphan genes.Nature reviews. Genetics · 2011Review
- Detection of functional overlapping genes: simulation and case studies.Journal of molecular evolution · 2010Article
- Non-random retention of protein-coding overlapping genes in Metazoa.BMC genomics · 2008Article
- Rapid asymmetric evolution of a dual-coding tumor suppressor INK4a/ARF locus contradicts its function.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- A first look at ARFome: dual-coding genes in mammalian genomes.PLoS computational biology · 2007Article
- The implications of alternative splicing in the ENCODE protein complement.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
XLalphas and ALEX are structurally unrelated mammalian proteins translated from alternative overlapping reading frames of a single transcript. Not only are they encoded by the same locus, but a specific XLalphas/ALEX interaction is essential for G-protein signaling in neuroendocrine cells. A disruption of this interaction leads to abnormal human phenotypes, including mental retardation and growth deficiency. The region of overlap between the two reading frames evolves at a remarkable speed: the divergence between human and mouse ALEX polypeptides makes them virtually unalignable. To trace the evolution of this puzzling locus, we sequenced it in apes, Old World monkeys, and a New World monkey. We show that the overlap between the two reading frames and the physical interaction between the two proteins force the locus to evolve in an unprecedented way. Namely, to maintain two overlapping protein-coding regions the locus is forced to have high GC content, which significantly elevates its intrinsic evolutionary rate. However, the two encoded proteins cannot afford to change too quickly relative to each other as this may impair their interaction and lead to severe physiological consequences. As a result XLalphas and ALEX evolve in an oscillating fashion constantly balancing the rates of amino acid replacements. This is the first example of a rapidly evolving locus encoding interacting proteins via overlapping reading frames, with a possible link to the origin of species-specific neurological differences.
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