Transcription profiling of human, chimp and mouse brain

Microarray technologies allow the identification of large numbers of expression differences within and between species. Although environmental and physiological stimuli are clearly responsible for changes in the expression levels of many genes, it is not known whether the majority of changes of gene expression fixed during evolution between species and between various tissues within a species are caused by Darwinian selection or by stochastic processes. We find the following: (1) expression differences between species accumulate approximately linearly with time; (2) gene expression variation among individuals within a species correlates positively with expression divergence between species; (3) rates of expression divergence between species do not differ significantly between intact genes and expressed pseudogenes; (4) expression differences between brain regions within a species have accumulated approximately linearly with time since these regions emerged during evolution. These results suggest that the majority of expression differences observed between species are selectively neutral or nearly neutral and likely to be of little or no functional significance. Therefore, the identification of gene expression differences between species fixed by selection should be based on null hypotheses assuming functional neutrality. Furthermore, it may be possible to apply a molecular clock based on expression differences to infer the evolutionary history of tissues.微阵列技术（Microarray）可用于检测物种内部及物种间的大量基因表达差异。尽管环境与生理刺激显然是众多基因表达水平变化的诱因，但目前仍无法明确：物种间以及物种内不同组织间在演化过程中固定下来的多数基因表达改变，究竟是由达尔文选择驱动，还是由随机过程导致。本研究得到如下发现：(1) 物种间的基因表达差异随时间大致呈线性积累；(2) 同一物种内个体间的基因表达变异与物种间的表达分化呈显著正相关；(3) 物种间的表达分化速率在完整基因与表达型假基因（expressed pseudogenes）之间无显著差异；(4) 某一物种内不同脑区间的表达差异，自这些脑区在演化中形成以来，随时间大致呈线性积累。上述结果表明，当前观测到的物种间多数表达差异属于选择中性或近中性，且大概率几乎不具备或完全不具备功能意义。因此，若要鉴定由选择固定下来的物种间基因表达差异，应当以假定功能中性的零假设作为检验基础。此外，基于表达差异的分子钟（molecular clock）或可用于推断组织的演化历史。