Abstract
The Nanog gene plays a key role in the pluripotency of early embryonic cells in vitro and in vivo. In this article retrotransposed copies of Nanog, termed NanogPc and NanogPd, are identified on mouse Chromosomes 4 and 7, respectively. In contrast to the two previously characterized mouse Nanog retrogenes that contain multiple frameshifts and point mutations, NanogPc and NanogPd are 98% identical to NANOG within the open reading frame and encode proteins with activity in an embryonic stem cell self-renewal assay. Mutations common to all four retrotransposed genes but distinct from Nanog suggest divergence from a common progenitor that appears likely to be Nanog because transcripts derived from Nanog but not from the retrogenes are detected in germ-line cells. The possibility that expression of Nanog could be erroneously attributed to novel cellular sources is suggested by the high homology among Nanog, NanogPc, and NanogPd. Analysis of distinct Mus species suggests that NanogPc and NanogPd arose between divergence of M. caroli and M. spretus and indicates that Nanog retrotransposition events continue to occur at a high frequency, a property likely to extend to other germ-line transcripts.
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Acknowledgments
The authors thank Susan Hunter and Martin Evans and Phil Avner for DNA from 129/SvEv and M. spretus, respectively. They also thank Simon Tomlinson for help with Supplemental Fig. 1 and Peter Holland and Austin Smith for their comments on the manuscript. This research was supported by the Biotechnology and Biological Sciences Research Council, the Medical Research Council of the UK, and by a Wellcome Trust VIP award to IC.
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Nucleotide sequence data reported here are available in the GenBank database under accession numbers DQ358089, DQ358090, DQ358091, DQ358092, DQ358093, DQ358094, DQ358095, DQ358096.
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Robertson, M., Stenhouse, F., Colby, D. et al. Nanog retrotransposed genes with functionally conserved open reading frames. Mamm Genome 17, 732–743 (2006). https://doi.org/10.1007/s00335-005-0131-y
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DOI: https://doi.org/10.1007/s00335-005-0131-y