Stenøien Hans K, Stephan Wolfgang
Plant Ecology/Department of Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, SE-752 36, Uppsala, Sweden.
J Mol Evol. 2005 Sep;61(3):306-14. doi: 10.1007/s00239-004-0271-9. Epub 2005 Jul 21.
A multitude of factors contribute to the regulation of gene expression in living cells. The relationship between codon usage bias and gene expression has been extensively studied, and it has been shown that codon bias may have adaptive significance in many unicellular and multicellular organisms. Given the central role of mRNA in post-transcriptional regulation, we hypothesize that mRNA stability is another important factor associated either with positive or negative regulation of gene expression. We have conducted genome-wide studies of the association between gene expression (measured as transcript abundance in public EST databases), mRNA stability, codon bias, GC content, and gene length in Drosophila melanogaster. To remove potential bias of gene length inherently present in EST libraries, gene expression is measured as normalized transcript abundance. It is demonstrated that codon bias and GC content in second codon position are positively associated with transcript abundance. Gene length is negatively associated with transcript abundance. The stability of thermodynamically predicted mRNA secondary structures is not associated with transcript abundance, but there is a negative correlation between mRNA stability and codon bias. This finding does not support the hypothesis that codon bias has evolved as an indirect consequence of selection favoring thermodynamically stable mRNA molecules.
众多因素共同作用于活细胞中基因表达的调控。密码子使用偏好与基因表达之间的关系已得到广泛研究，结果表明密码子偏好可能在许多单细胞和多细胞生物中具有适应性意义。鉴于mRNA在转录后调控中的核心作用，我们推测mRNA稳定性是与基因表达的正调控或负调控相关的另一个重要因素。我们对黑腹果蝇中基因表达（以公共EST数据库中的转录本丰度衡量）、mRNA稳定性、密码子偏好、GC含量和基因长度之间的关联进行了全基因组研究。为消除EST文库中固有的基因长度潜在偏差，基因表达以标准化转录本丰度来衡量。结果表明，密码子偏好和第二密码子位置的GC含量与转录本丰度呈正相关。基因长度与转录本丰度呈负相关。热力学预测的mRNA二级结构的稳定性与转录本丰度无关，但mRNA稳定性与密码子偏好之间存在负相关。这一发现不支持密码子偏好是有利于热力学稳定mRNA分子的选择的间接结果这一假说。
