Regulatory sequences (e.g., transcription factor binding sites), unlike protein-coding regions, are subject to rapid turnover. 这句话来自(Webb Miller et.al., "Comparative Genomics", annual review of Genomics and Human Genetics Vol.5:15-56)
这句话后面跟了reference。在reference38的abstract中，作者提到："estimated that 32%-40% of the human functional sites are not functional in rodents. This is evidence that there is widespread turnover of transcription factor binding sites"
在introduction中，作者说到:"Individual binding sites may exhibit relatively little conservation, either because of the degeneracy of the transcription factor binding requirements or because their small size makes it relatively likely that a new functional site will arise by chance."
Challenges (in regulatory sequence identification) included the large non-coding search space in the human genome, the small size and degenerate nature of transcription factor binding sites, and most importantly the lack of experimental training sets for computational methods to identify such sequences in a global manner.
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