Isochores and tissue-specificity
Isochores and tissue-specificity
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DOI：
10.1093/nar/gkg699
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发表时间：
2003-09-01
影响因子：
14.9
通讯作者：
Vinogradov, AE
中科院分区：
文献类型：
--
作者：
Vinogradov, AE
哺乳动物基因组中的管家（普遍表达）基因平均比组织特异性基因稍微富含GC。管家基因和组织特异性基因占据相似的GC含量范围，但前者倾向于集中在范围的上部。在人类基因组中，组织特异性基因显示出两个最大值，GC-贫和GC-富。严格的组织特异性的人类基因往往集中在GC-穷人的地区，他们的分布是左偏，因此管家基因的分布倒数。中等组织特异性基因显示中等GC含量和右偏分布。在人类和小鼠中，对某些组织特异的基因（例如，中枢神经系统的一部分）比管家基因具有更高的平均GC含量。由于它们在生殖系中不转录（与管家基因相反），因此具有较低的遗传基因转换概率，这一发现与哺乳动物基因组重等位基因中GC含量升高的偏倚基因转换（BGC）解释相矛盾。生殖系组织（卵巢、睾丸）的特异性基因显示出较低的平均GC含量，这也与BGC的解释相矛盾。无论是总的数据集和大部分的组织单独采取，基因GC含量和表达水平之间的弱正相关。小鼠中普遍表达基因的比例比人类高近1.5倍。这表明小鼠组织相对较少分化（在分子水平上），这可能与小鼠基因组的不太明显的等容结构有关。在每一个单独的组织（在两个物种），组织特异性基因不形成一个明确的频率峰值（管家基因相反），但构成了一个连续的组织特异性程度逐渐增加，这可能反映了细胞分化的路径和/或在几个不相关的组织中独立使用相同的蛋白质。
The housekeeping (ubiquitously expressed) genes in the mammal genome were shown here to be on average slightly GC-richer than tissue-specific genes. Both housekeeping and tissue-specific genes occupy similar ranges of GC content, but the former tend to concentrate in the upper part of the range. In the human genome, tissue-specific genes show two maxima, GC-poor and GC-rich. The strictly tissue-specific human genes tend to concentrate in the GC-poor region; their distribution is left-skewed and thus reciprocal to the distribution of housekeeping genes. The intermediately tissue-specific genes show an intermediate GC content and the right-skewed distribution. Both in the human and mouse, genes specific for some tissues (e.g., parts of the central nervous system) have a higher average GC content than housekeeping genes. Since they are not transcribed in the germ line (in contrast to housekeeping genes), and therefore have a lower probability of inheritable gene conversion, this finding contradicts the biased gene conversion (BGC) explanation for elevated GC content in the heavy isochores of mammal genome. Genes specific for germ-line tissues (ovary, testes) show a low average GC content, which is also in contradiction to the BGC explanation. Both for the total data set and for the most part of tissues taken separately, a weak positive correlation was found between gene GC content and expression level. The fraction of ubiquitously expressed genes is nearly 1.5-fold higher in the mouse than in the human. This suggests that mouse tissues are comparatively less differentiated (on the molecular level), which can be related to a less pronounced isochoric structure of the mouse genome. In each separate tissue (in both species), tissue-specific genes do not form a clear-cut frequency peak (in contrast to housekeeping genes), but constitute a continuum with a gradually increasing degree of tissue-specificity, which probably reflects the path of cell differentiation and/or an independent use of the same protein in several unrelated tissues.