Evolution of the NANOG pseudogene family in the human and chimpanzee genomes.
BACKGROUND
The NANOG gene is expressed in mammalian embryonic stem cells where it maintains cellular pluripotency. An unusually large family of pseudogenes arose from it with one unprocessed and ten processed pseudogenes in the human genome. This article compares the NANOG gene and its pseudogenes in the human and chimpanzee genomes and derives an evolutionary history of this pseudogene family.


RESULTS
The NANOG gene and all pseudogenes except NANOGP8 are present at their expected orthologous chromosomal positions in the chimpanzee genome when compared to the human genome, indicating that their origins predate the human-chimpanzee divergence. Analysis of flanking DNA sequences demonstrates that NANOGP8 is absent from the chimpanzee genome.


CONCLUSIONS
Based on the most parsimonious ordering of inferred source-gene mutations, the deduced evolutionary origins for the NANOG pseudogene family in the human and chimpanzee genomes, in order of most ancient to most recent, are NANOGP6, NANOGP5, NANOGP3, NANOGP10, NANOGP2, NANOGP9, NANOGP7, NANOGP1, and NANOGP4. All of these pseudogenes were fixed in the genome of the human-chimpanzee common ancestor. NANOGP8 is the most recent pseudogene and it originated exclusively in the human lineage after the human-chimpanzee divergence. NANOGP1 is apparently an unprocessed pseudogene. Comparison of its sequence to the functional NANOG gene's reading frame suggests that this apparent pseudogene remained functional after duplication and, therefore, was subject to selection-driven conservation of its reading frame, and that it may retain some functionality or that its loss of function may be evolutionarily recent.
Department of Plant and Animal Sciences, Brigham Young University, Provo, UT 84602, USA. daniel_fairbanks@byu.edu
Daniel J
DJ
Fairbanks
Peter J
PJ
Maughan
D000818:Animals; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D016368:Frameshift Mutation; D020440:Gene Duplication; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008322:Mammals / Q000235:genetics; D005810:Multigene Family; D000071317:Nanog Homeobox Protein; D016366:Open Reading Frames; D002679:Pan troglodytes / Q000235:genetics*; D010802:Phylogeny; D011544:Pseudogenes; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013997:Time Factors
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein