Data from: Mixed-model reanalysis of primate data suggests tissue and species biases

An emerging issue in evolutionary genetics is whether it is possible to use gene expression profiling to identify genes that are associated with morphological, physiological, or behavioral divergence between species and whether these genes have undergone positive selection. Some of these questions were addressed in a recent study (Enard et al. 2002) of the difference in gene expression among human, chimp, and orangutan, which suggested an accelerated rate of divergence in gene expression in the human brain relative to liver. Reanalysis of the Affymetrix data set using analysis of variance methods to quantify the contributions of individuals and species to variation in expression of 12,600 genes indicates that as much as one-quarter of the genome shows divergent expression between primate species at the 5% level. The magnitude of fold change ranges from 1.2-fold up to 8-fold. Similar conclusions apply to reanalysis of Enard et al. 2002 parallel murine data set. However, biases inherent to short oligonucleotide microarray technology may account for some of the tissue and species effects. At high significance levels, more differences were observed in the liver than in the brain in each of the pairwise species comparisons, so it is not clear that expression divergence is accelerated in the human brain. Further, there is an apparent bias toward upregulation of gene expression in the brain in both primates and mice, whereas genes are equally likely to be up- or downregulated in the liver when these species diverge. A small subset of genes that are candidates for adaptive divergence may be identified on the basis of a high ratio of interspecific to intraspecific divergence.进化遗传学领域的一个新兴议题是，能否通过基因表达谱分析（gene expression profiling）识别与物种间形态、生理或行为分化相关的基因，以及这些基因是否经历了正向选择（positive selection）。此前一项针对人类、黑猩猩与红毛猩猩的基因表达差异研究（Enard等，2002）已对部分此类问题展开探讨，该研究指出，相较于肝脏组织，人类大脑的基因表达分化速率更快。本研究通过方差分析（analysis of variance）方法重新分析该Affymetrix数据集，量化了个体与物种对12600个基因的表达变异的贡献程度，结果显示，在5%的显著性水平下，多达四分之一的基因组在灵长类物种间呈现表达分化，其表达差异的倍数变化幅度介于1.2倍至8倍之间。对Enard等2002年的平行小鼠数据集（murine data set）进行的重新分析也得到了相似结论。不过，短寡核苷酸微阵列技术（short oligonucleotide microarray technology）固有的偏倚或许可以解释部分组织与物种效应。在较高的显著性水平下，每一组物种两两比较中，肝脏组织中观测到的表达差异均多于大脑组织，因此尚无法确定人类大脑的基因表达分化确实更快。进一步而言，在灵长类与小鼠的大脑中均存在基因表达上调（upregulation）的明显偏倚；而当这些物种发生分化时，肝脏组织中基因的上调与下调概率并无显著差异。基于种间分化与种内分化的高比值，可筛选出一小部分适应性分化候选基因。