华新 - 关于life science的问题：regulatory sequence - turnover and degenerate nature

关于life science的问题：regulatory sequence - turnover and degenerate nature

作者：水鸭子 (等级：14 - 天人和一，发帖：9284) 发表：2008-04-05 18:45:41　楼主　关注此帖评分：

关于life science的问题：regulatory sequence - turnover and degenerate nature

Regulatory sequences (e.g., transcription factor binding sites), unlike protein-coding regions, are subject to rapid turnover.

Challenges (in regulatory sequence identification) included the large non-coding search space in the human genome (98% of 3×109 bp), 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.

上面是paper里头的原话。搞不明白这里的turnover和degenerate nature是不是一个意思？是指sequence本身会变化（mutation, etc.），还是说transcriotion factor is not binding to this cis element?

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作者：Johnny.R (等级：2 - 初出茅庐，发帖：113) 发表：2008-04-08 21:55:51　 2楼评分：

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我觉得有相同的意思

但turnover指的应该不是sequence本身的变化，而是一个regulatory sequence被另一个regulatory sequence所取代。

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."

所以我的理解是，Turnover指的是一个regulatory sequence被另一个regulatory sequence所取代。
在进化中，由于regulatory sequence相对较短，以及transcription factor与之结合的条件不断变化，使得基因组里能不断冒出新的functional sites (by chance)，并取代原有的regulatory sequence。

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.

这里面的"degenarate nature"我觉得也有消失，作废的意思。环境的变化对物种不断提出新的要求，物种体内的基因也要发生相应变化。而照上面作者的意思，基因组中不断随机冒出新的sequence中会出现更加适应新环境需求的regulatory sites,从而取代旧的regulatory sequence，并使其degenerate.和protein coding sequence相比，这些regulatory sequence变化速度较快。

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作者：水鸭子 (等级：14 - 天人和一，发帖：9284) 发表：2008-04-29 18:08:00　 3楼评分：

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在 Johnny.R 的大作中提到：

我觉得有相同的意思但turnover指的应该不是sequence本身的变化，而是一个regulatory sequence被另一个regulatory sequence所取代。 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." 所以我的理解是，Turnover指的是一个regulatory sequence被另一个regulatory sequence所取代。在进化中，由于regulatory sequence相对较短，以� (more...)

非常感谢

可惜有点迟。
当时在写project term paper
因为没搞懂这个问题，当时就随便糊弄过去了（避免了这个话题，没特别写）

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