From Novel PAX6 Binding Sites in the Human Genome and the Role of Repetitive Elements in the Evolution of Gene Regulation, by Yi-Hong Zhou, Jessica B. Zheng, Xun Gu, Grady F. Saunders, and W.-K. Alfred Yung.
Pax6 is a transcription factor that plays a very important role in development:
Pax6 is an important regulator of transcription in the development of the eye and central nervous system in vertebrates and invertebrates. The protein sequence and function of Pax6 are evolutionarily conserved so that murine and human Pax6 proteins are identical. Even human and zebrafish Pax6 proteins share a 97% homology. With few exceptions, Pax6 is expressed during central nervous system development and during fundamental sensory processes, particularly of the photoreceptive organ. The expression of Pax6 in adult mammals is restricted to the eye, brain, and pancreas.
And guess what?
Through an in vitro protein–DNA binding approach, we identified three new types of PAX6 binding sequences in the human genome. Two exist in a single copy in genome, and one within Alu repetitive elements.
These observations led to a putative evolutionary scenario that describes how a transcription factor (Pax6) recruits new target genes in the genome. Mediated by repetitive elements and mutations in CpG dinucleotide hot spots (e.g., Alu or B1), several types of Pax6 binding sites have been generated and were spread over the entire genome.
Mutations in CpG hotspots – cytosine deamination.
Need I say more?
What’s that? B1? Oh, that’s a good one too.