Inferred divergent gene regulation in archaic hominins reveals potential phenotypic differences
Inferred divergent gene regulation in archaic hominins reveals potential phenotypic differences
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DOI：
10.1038/s41559-019-0996-x
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发表时间：
2019-11-01
影响因子：
16.8
通讯作者：
Capra, John A.
中科院分区：
文献类型：
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作者：
Colbran, Laura L.;Gamazon, Eric R.;Capra, John A.
对来自古代骨骼的DNA进行测序，可以对尼安德特人和解剖学上的现代人（AMH）进行基因比较，并揭示他们进行了杂交。然而，解释遗传差异意味着它们的表型差异仍然具有挑战性。在这里，我们介绍了一种方法，用于确定古人类，如尼安德特人，和AMH序列之间的分歧基因调控，并找到766个基因，很可能已分歧调节（DR）的尼安德特人的单倍型，不留在AMH。DR基因包括许多与尼安德特人和AMH之间已知不同的表型有关的基因，例如胸腔结构和眶上嵴发育。它们还富含与自然流产、多囊卵巢综合征、心肌梗死和黑色素瘤相关的基因。在类似于23，000名生物库患者中，与这些基因调控中的现代人类变异相关的表型进一步支持它们参与免疫和心血管表型。比较两个尼安德特人和一个丹尼索瓦人之间的DR基因，发现免疫系统和与骨骼和牙齿形态相关的基因存在分歧，这与考古记录一致。这些结果建立AMH和古人类之间的基因调控结构的差异，并提供了一个途径，从基因组信息单独探索古群体之间的表型差异。
Sequencing DNA derived from archaic bones has enabled genetic comparison of Neanderthals and anatomically modern humans (AMHs), and revealed that they interbred. However, interpreting what genetic differences imply about their phenotypic differences remains challenging. Here, we introduce an approach for identifying divergent gene regulation between archaic hominins, such as Neanderthals, and AMH sequences, and find 766 genes that are likely to have been divergently regulated (DR) by Neanderthal haplotypes that do not remain in AMHs. DR genes include many involved in phenotypes known to differ between Neanderthals and AMHs, such as the structure of the rib cage and supraorbital ridge development. They are also enriched for genes associated with spontaneous abortion, polycystic ovary syndrome, myocardial infarction and melanoma. Phenotypes associated with modern human variation in these genes' regulation in similar to 23,000 biobank patients further support their involvement in immune and cardiovascular phenotypes. Comparing DR genes between two Neanderthals and a Denisovan revealed divergence in the immune system and in genes associated with skeletal and dental morphology that are consistent with the archaeological record. These results establish differences in gene regulatory architecture between AMHs and archaic hominins, and provide an avenue for exploring phenotypic differences between archaic groups from genomic information alone.