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NANOGP8: evolution of a human-specific retro-oncogene
Daniel J Fairbanks1, Aaron D Fairbanks, T Heath Ogden
1Department of Biology, Utah Valley University, 800 W.University Parkway, Orem, UT 84058, USA. daniel.fairbanks@uvu.edu
G3 (Bethesda, Md.)
|November 23, 2012
Summary
The human NANOGP8 retrogene, a cancer-promoting gene, originated 0.9-2.5 million years ago from a NANOG variant. NANOGP8 is present in humans and Neanderthals, potentially explaining human cancer predisposition.
Area of Science:
- Evolutionary biology
- Genetics
- Oncology
Background:
- NANOGP8 is a human retrogene derived from NANOG, predominantly expressed in cancer cells and implicated in tumorigenesis.
- Its evolutionary origin and relationship with the parent NANOG gene, particularly in the context of human evolution and cancer, require further investigation.
Purpose of the Study:
- To precisely estimate the evolutionary origin of the human NANOGP8 retrogene.
- To investigate the specific NANOG allele from which NANOGP8 arose and its evolutionary fate.
- To determine the presence of NANOGP8 in Neanderthals and its implications for human cancer predisposition.
Main Methods:
- Comparative genomic analysis of human and Neanderthal sequences.
- Identification and characterization of fixed and polymorphic variants in NANOG and NANOGP8.
- Phylogenetic analysis to estimate evolutionary timelines.
Main Results:
- NANOGP8 originated approximately 0.9 to 2.5 million years ago, more recently than previously estimated.
- NANOGP8 arose from a NANOG allele with a 22-nucleotide deletion in the 3' UTR, which remains polymorphic.
- NANOGP8 is fixed in modern humans and was also present in Neanderthals.
- Some commonly used variants for distinguishing NANOG and NANOGP8 are unreliable due to polymorphism.
Conclusions:
- NANOGP8 is a human-specific retro-oncogene with an evolutionary history intertwined with human and Neanderthal populations.
- Its retrotransposition and potential regulation by nearby elements may contribute to cancer susceptibility in humans.
- The findings necessitate re-evaluation of diagnostic methods relying on NANOG/NANOGP8 sequence differences.
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