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项新兴议题为：能否借助基因表达谱（gene expression profiling）技术，鉴定出与物种间形态、生理或行为分化相关的基因，同时明确这些基因是否经历了正向选择（positive selection）。埃纳德等人（Enard et al. 2002）在近期一项针对人类、黑猩猩与红毛猩猩的基因表达差异研究中，对部分此类问题展开了探讨。该研究提出，相较于肝脏组织，人类大脑的基因表达分化速率有所加快。本研究通过方差分析（analysis of variance）方法，对该Affymetrix数据集进行重新分析，以量化个体与物种对12600个基因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存在表达分化，其折叠变化（fold change）幅度介于1.2倍至8倍之间。针对埃纳德等人2002年的平行小鼠数据集的重新分析，也得到了相似结论。不过，短寡核苷酸微阵列技术（short oligonucleotide microarray technology）本身固有的偏倚，或许可以部分解释组织与物种效应的产生。在较高的显著性水平下，每一组物种两两比较中，肝脏中观测到的表达差异均多于大脑，因此目前尚无法确定人类大脑的基因表达分化速率确实更快。此外，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；而在物种分化过程中，肝脏内基因的上调与下调（downregulation）概率基本相当。可基于种间分化（interspecific divergence）与种内分化（intraspecific divergence）的高比值，筛选出少量作为适应性分化（adaptive divergence）候选基因的基因子集。