Functional diversification of paralogous transcription factors via divergence in DNA binding site motif and in expression.
Functional diversification of paralogous transcription factors via divergence in DNA binding site motif and in expression.
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DOI：
10.1371/journal.pone.0002345
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发表时间：
2008-06-04
期刊：
影响因子：
3.7
通讯作者：
Hannenhalli, Sridhar
中科院分区：
文献类型：
--
作者：
Singh, Larry N.;Hannenhalli, Sridhar
基因复制是进化创新的主要驱动力，因为它允许生物体通过最初冗余的基因旁系同源物的专业化或多样化来阐述其现有的生物功能。基因功能可以通过几种方式多样化。特别是转录因子基因旁系同源物，可以通过其组织特异性表达模式的变化或通过其蛋白质产物识别的DNA结合位点基序的变化而多样化，这反过来又改变了其基因靶标。这两种模式的功能多样化的转录因子旁系同源物之间的关系还没有以前的研究，是必不可少的理解适应性进化的转录因子基因家族。基于大量的人类旁系同源转录因子对，我们表明，当转录因子旁系同源物的DNA结合位点基序是相似的，编码旁系同源物的基因的表达有分歧，所以在一般情况下，在最多的旁系同源物之一是在组织中高度表达。此外，具有不同DNA结合位点基序的旁系同源物在功能上往往会出现分歧。相反，在组织中高度表达的两种旁系同源物倾向于具有不同的DNA结合位点基序。我们还发现，在一般情况下，在一个旁系同源的家庭，组织特异性的基因表达下降是更频繁的比什么是预期的机会。虽然以前的调查旁系同源基因多样化只考虑编码序列的分歧，明确量化分歧的DNA结合位点基序，我们的工作提出了一个新的范式，调查功能多样化。与进化的预期一致，我们的定量分析表明，旁系同源转录因子的生存灭绝的一部分，无论是通过其DNA结合位点基序的多样化或通过改变其组织特异性表达水平。
Gene duplication is a major driver of evolutionary innovation as it allows for an organism to elaborate its existing biological functions via specialization or diversification of initially redundant gene paralogs. Gene function can diversify in several ways. Transcription factor gene paralogs in particular, can diversify either by changes in their tissue-specific expression pattern or by changes in the DNA binding site motif recognized by their protein product, which in turn alters their gene targets. The relationship between these two modes of functional diversification of transcription factor paralogs has not been previously investigated, and is essential for understanding adaptive evolution of transcription factor gene families. Based on a large set of human paralogous transcription factor pairs, we show that when the DNA binding site motifs of transcription factor paralogs are similar, the expressions of the genes that encode the paralogs have diverged, so in general, at most one of the paralogs is highly expressed in a tissue. Moreover, paralogs with diverged DNA binding site motifs tend to be diverged in their function. Conversely, two paralogs that are highly expressed in a tissue tend to have dissimilar DNA binding site motifs. We have also found that in general, within a paralogous family, tissue-specific decrease in gene expression is more frequent than what is expected by chance. While previous investigations of paralogous gene diversification have only considered coding sequence divergence, by explicitly quantifying divergence in DNA binding site motif, our work presents a new paradigm for investigating functional diversification. Consistent with evolutionary expectation, our quantitative analysis suggests that paralogous transcription factors have survived extinction in part, either through diversification of their DNA binding site motifs or through alterations in their tissue-specific expression levels.
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DOI：
10.1073/pnas.94.13.6809
发表时间：
1997-06-24
影响因子：
11.1
作者：
Gaut, BS;Doebley, JF
通讯作者：
Doebley, JF
TransFac及其模块移植：真核生物中的转录基因调节。
影响因子：
14.9
作者：
Matys V;Kel-Margoulis OV;Fricke E;Liebich I;Land S;Barre-Dirrie A;Reuter I;Chekmenev D;Krull M;Hornischer K;Voss N;Stegmaier P;Lewicki-Potapov B;Saxel H;Kel AE;Wingender E
通讯作者：
Wingender E
影响因子：
3
作者：
Harrison, Andrew P;Johnston, Caroline E;Orengo, Christine A
通讯作者：
Orengo, Christine A
影响因子：
14.9
作者：
Sandelin, A;Alkema, W;Lenhard, B
通讯作者：
Lenhard, B
影响因子：
4.3
作者：
Mahony, Shaun;Auron, Philip E.;Benos, Panayiotis V.
通讯作者：
Benos, Panayiotis V.