Nadezhdin E V, Vinogradova T V, Sverdlov E D
Bioorg Khim. 2004 Jul-Aug;30(4):383-8. doi: 10.1023/b:rubi.0000037260.47799.52.
A full genome analysis of differences between the gene expression in the human and chimpanzee brains revealed that the gene for transthyretin, the carrier of thyroid hormones, is differently transcribed in the cerebella of these species. A 7-kbp DNA fragment of chimpanzee was sequenced to identify possible regulatory sequences responsible for the differences in expression. One hundred and thirteen substitutions were found in the chimpanzee sequence in comparison with the human sequence. About 40% of the substitutions were revealed within the repeating elements of the genome; their location and sizes did not differ from those in the corresponding fragments of the human genome, and the nucleotide sequences had a high degree of identity. A comparison of nucleotide sequences of the transthyretin region of human, chimpanzee, and mouse genes revealed substantial differences in the distribution of G + C content along the examined fragment in the human (chimpanzee) and mouse genes and allowed us to localize three sequence tracts with a higher degree of identity in the three species. One of these tracts is located in the promoter region of the gene, and the other two probably determine the specificity of transthyretin gene expression in the liver and brain. One of the conserved tracts of the chimpanzee genome was found to have a single and a triple nucleotide substitution. The triple substitution distinguishes chimpanzees from humans and mice, which have identical sequences of this site. It is likely that these substitutions are responsible for the differences in the expression levels of the transthyretin gene in the human and chimpanzee brains.
对人类和黑猩猩大脑中基因表达差异进行的全基因组分析表明，甲状腺激素载体转甲状腺素蛋白的基因在这两个物种的小脑中转录方式不同。对黑猩猩的一个7千碱基对的DNA片段进行测序，以确定造成表达差异的可能调控序列。与人类序列相比，在黑猩猩序列中发现了113个替换位点。约40%的替换位点存在于基因组的重复元件中；它们的位置和大小与人类基因组相应片段中的位置和大小并无差异，且核苷酸序列具有高度同一性。对人类、黑猩猩和小鼠转甲状腺素蛋白基因区域的核苷酸序列进行比较，发现人类（黑猩猩）和小鼠基因中，在所检测片段上G + C含量的分布存在显著差异，并使我们能够在这三个物种中定位出三个具有较高同一性的序列片段。其中一个片段位于该基因的启动子区域，另外两个片段可能决定了转甲状腺素蛋白基因在肝脏和大脑中表达的特异性。在黑猩猩基因组的一个保守片段中发现了一个单核苷酸替换和一个三核苷酸替换。这个三核苷酸替换使黑猩猩与人类和小鼠区分开来，后两者在该位点的序列相同。很可能这些替换导致了人类和黑猩猩大脑中转甲状腺素蛋白基因表达水平的差异。
