University of Barcelona, Barcelona, Spain.
University of Barcelona Institute of Complex Systems, Barcelona, Spain.
BMC Genom Data. 2022 May 11;23(1):36. doi: 10.1186/s12863-022-01048-8.
The availability of high-coverage genomes of our extinct relatives, the Neanderthals and Denisovans, and the emergence of large, tissue-specific databases of modern human genetic variation, offer the possibility of probing the effects of modern-derived alleles in specific tissues, such as the brain, and its specific regions. While previous research has explored the effects of introgressed variants in gene expression, the effects of Homo sapiens-specific gene expression variability are still understudied. Here we identify derived, Homo sapiens-specific high-frequency (≥90%) alleles that are associated with differential gene expression across 15 brain structures derived from the GTEx database. We show that regulation by these derived variants targets regions under positive selection more often than expected by chance, and that high-frequency derived alleles lie in functional categories related to transcriptional regulation. Our results highlight the role of these variants in gene regulation in specific regions like the cerebellum and pituitary.
我们灭绝的近亲尼安德特人和丹尼索瓦人的高覆盖率基因组的可用性，以及现代人类遗传变异的大型、组织特异性数据库的出现，为研究现代衍生等位基因在特定组织（如大脑及其特定区域）中的作用提供了可能。虽然之前的研究已经探索了基因表达中内源性变异的影响，但人类特异性基因表达可变性的影响仍有待研究。在这里，我们鉴定了与 GTEx 数据库中 15 种大脑结构的基因表达差异相关的、衍生的、人类特异性的高频（≥90%）等位基因。我们表明，这些衍生变异的调控作用比预期的更经常靶向正选择区域，并且高频衍生等位基因位于与转录调控相关的功能类别中。我们的研究结果强调了这些变体在特定区域（如小脑和垂体）的基因调控中的作用。
