Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain.
Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain.
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DOI：
10.1093/gbe/evq002
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发表时间：
2010-01-18
影响因子：
3.3
通讯作者：
Wray GA
中科院分区：
文献类型：
--
作者：
Babbitt CC;Fedrigo O;Pfefferle AD;Boyle AP;Horvath JE;Furey TS;Wray GA
尽管人类和我们最近的灵长类亲属在认知和行为上存在显着差异，但几项研究几乎没有发现主要在大脑中表达的基因的蛋白质编码区发生适应性变化的证据。相反，基因表达的变化可能是许多认知和行为差异的基础。在这里，我们使用数字基因表达：标签分析（这里称为Tag-Seq，也称为DGE：标签分析）来评估3名人类，3名黑猩猩和3名恒河猴大脑额叶皮层中的整体转录本丰度的变化。在以前的研究中，我们确定的物种之间的差异转录的转录本的很大一部分没有进行分析的基础上的微阵列。编码区内差异表达的标签富集了参与突触传递、转运、氧化磷酸化和脂质代谢的基因功能。重要的是，由于Tag-Seq技术提供了关于所有多聚腺苷酸化转录物的链特异性信息，我们能够测定非编码基因内区域的表达，包括正义和反义非编码转录物（相对于附近的基因）。我们发现，许多非编码转录本在物种之间的位置和表达水平上都是保守的，这表明可能的功能作用。最后，我们研究了差异基因表达和假定的启动子区域内的正选择签名之间的重叠，这些差异代表了人类进化过程中的适应性。比较方法可能会提供重要的见解基因负责人类和非人灵长类动物之间的认知功能的差异，以及突出新的候选基因的研究调查神经系统疾病。
Despite striking differences in cognition and behavior between humans and our closest primate relatives, several studies have found little evidence for adaptive change in protein-coding regions of genes expressed primarily in the brain. Instead, changes in gene expression may underlie many cognitive and behavioral differences. Here, we used digital gene expression: tag profiling (here called Tag-Seq, also called DGE:tag profiling) to assess changes in global transcript abundance in the frontal cortex of the brains of 3 humans, 3 chimpanzees, and 3 rhesus macaques. A substantial fraction of transcripts we identified as differentially transcribed among species were not assayed in previous studies based on microarrays. Differentially expressed tags within coding regions are enriched for gene functions involved in synaptic transmission, transport, oxidative phosphorylation, and lipid metabolism. Importantly, because Tag-Seq technology provides strand-specific information about all polyadenlyated transcripts, we were able to assay expression in noncoding intragenic regions, including both sense and antisense noncoding transcripts (relative to nearby genes). We find that many noncoding transcripts are conserved in both location and expression level between species, suggesting a possible functional role. Lastly, we examined the overlap between differential gene expression and signatures of positive selection within putative promoter regions, a sign that these differences represent adaptations during human evolution. Comparative approaches may provide important insights into genes responsible for differences in cognitive functions between humans and nonhuman primates, as well as highlighting new candidate genes for studies investigating neurological disorders.
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