尼安德特人、丹尼索瓦人基因组的发现及其对现代人类的影响

Discovery of genomes of Neanderthal,Denisova and its impact on modern human

2022年度诺贝尔生理学或医学奖授予瑞典生物学家、进化遗传学权威斯万特·帕博(Svante P??bo),以表彰他“在已灭绝古人类基因组和人类进化方面的发现”所作出的突出贡献.人类之所以为“人”是科学家们一直以来感兴趣的研究方向,Svante P??bo针对尼安德特人和丹尼索瓦人的研究有助于进一步加深对人类演化进程的理解,意义重大.他发现基因交流存在于早期的不同古人类之间,现代人类的基因组中含有已灭绝古人类的基因序列,比例不大,却在生理和病理方面影响着当今人类.本文简要总结了Svante P??bo的研究发现,并介绍遗传自尼安德特人和丹尼索瓦人的基因在新型冠状病毒肺炎(COVID-19)、免疫功能和低氧适应等方面是如何影响当今人类的.

The 2022 Nobel Prize in Physiology or Medicine was surprisingly awarded to Svante Paabo for his establishment of a novel discipline,paleogenomics.Paleogenomics offers a potent means of understanding the course of modern human evolution.Paabo’s research lays a solid foundation for answering the question of what makes us,Homo sapiens,different from other hominins.This year’s Nobel laureate has observed genetic admixture in different groups of archaic humans,and found that parts of the genetic code of these extinct branches of the human evolutionary tree are present in the genomes of modern humans,influencing us both physiologically and pathologically.In this paper,Paabo’s research findings are first summarized to deepen,consolidate,and broaden the understanding of extinct hominins and paleogenomics.Paabo’s team was responsible for the first draft sequence of the Neanderthal genome,showing that between 1.5%and 2.1%of modern Eurasian genomes are derived from Neanderthals.They followed this with the complete Neanderthal genome sequence.Similarly,Paabo and colleagues published both the first draft and the complete sequence of the Denisovan genome.They found evidence of genetic admixture between the Denisovans and modern humans,showing that the genomes of people in Oceania are between 3%and 6%Denisovan while the figure for people in Asia is about 0.2%.Furthermore,at least 0.5%of the Denisovan genome was derived from the Neanderthals.The COVID-19 pandemic provided evidence of the good and bad qualities of the Neanderthal inheritance,particularly in relation to the immune systems of modern humans.A gene cluster on chromosome 3 that was inherited from Neanderthals was found to be associated with severe COVID-19.This gene cluster is mainly found in modern humans from the Middle East and southern Asia.Several genes included in this cluster have been demonstrated to play a role in immune functions and may be involved in the infection process of SARS-CoV-2.Interestingly,a gene segment on chromosome 12 which was also inherited from Neanderthals is protective against severe COVID-19.This gene segment is mainly distributed in inhabitants of Europe,Asia,and the Americas,but not of Africa and Oceania.This segment contains the OAS1 gene which encodes proteins that activate enzymes that are important during RNA-viral infections.This is part of the reason why carrying this gene segment can reduce the risk of developing severe COVID-19.The Neanderthals have contributed many immune-related genes to modern humans,including the welldocumented cluster containing the TLR1,TLR6,and TLR10 genes.TLR1,TLR6,and TLR10 gene haplotypes inherited from Neanderthals show high expression frequencies in the genomes of Europeans and Asians.These three genes play important roles in the innate immune system that is the first line of defense against pathogens and can trigger adaptive immunity.The TLR1,TLR6,and TLR10 haplotypes increase the expression of their encoded proteins,which not only enhances innate immunity but can also induce hypersensitivity resulting in allergy.Lastly,the way in which Denisovan genes affect Tibetan and Nepalese people to adapt to the extreme conditions of the Qinghai-Tibet Plateau and the Himalayas,respectively,are discussed.The EPAS1 gene in Tibetans and Nepalese is inherited from the Denisovans and encodes the hypoxia-inducible factor HIF-2α,a transcription factor involved in the body’s response to low-oxygen conditions.That is to say,both Tibetan and Nepalese people are well adapted to hypoxic and cold conditions thanks to a gene inherited from the Denisovans.This paper intends to inspire more research into extinct hominins and paleogenomics,which can enhance our knowledge of certain diseases,allowing the development of new beneficial therapeutic targets.Thus,surprising results in a new field will eventually reap great benefits.