Oscillating evolution of a mammalian locus with overlapping reading frames: An XLαs/ALEX relay

Anton Nekrutenko, Samir Wadhawan, Paula Goetting-Minesky, Kateryna Dmytrivna Makova

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

XLαs 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 XLαs/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 XLαs 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.

Original languageEnglish (US)
Pages (from-to)197-204
Number of pages8
JournalPLoS genetics
Volume1
Issue number2
DOIs
StatePublished - Dec 1 2005

Fingerprint

Reading Frames
loci
protein
Proteins
Platyrrhini
Cercopithecidae
Neuroendocrine Cells
proteins
Hominidae
Base Composition
Cebidae
GTP-Binding Proteins
Intellectual Disability
Open Reading Frames
Pongidae
G-proteins
open reading frames
polypeptides
Phenotype
Amino Acids

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

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abstract = "XLαs 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 XLαs/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 XLαs 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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Oscillating evolution of a mammalian locus with overlapping reading frames : An XLαs/ALEX relay. / Nekrutenko, Anton; Wadhawan, Samir; Goetting-Minesky, Paula; Makova, Kateryna Dmytrivna.

In: PLoS genetics, Vol. 1, No. 2, 01.12.2005, p. 197-204.

Research output: Contribution to journalArticle

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