Press release: The Nobel Prize in Physiology or Medicine 2022

Nobel Svante Pääbo
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Press release: The Nobel Prize in Physiology or Medicine 2022

新闻发布。2022年诺贝尔生理学或医学奖

Press release新闻发布

2022-10-03

The Nobel Assembly at Karolinska Institutet卡罗林斯卡学院的诺贝尔奖大会

has today decided to award今天决定授予

the 2022 Nobel Prize in Physiology or Medicine 2022年诺贝尔生理学或医学奖

to授予

Svante Pääbo斯万特-派博

for his discoveries concerning the genomes of extinct hominins and human evolution

以表彰他对已灭绝人种的基因组和人类进化的发现

Humanity has always been intrigued by its origins. Where do we come from, and how are we related to those who came before us? What makes us, Homo sapiens, different from other hominins?人类一直对其起源感到好奇。我们从哪里来,我们与那些在我们之前的人有什么关系?是什么使我们,智人,与其他人类不同?

Through his pioneering research, Svante Pääbo accomplished something seemingly impossible: sequencing the genome of the Neanderthal, an extinct relative of present-day humans. He also made the sensational discovery of a previously unknown hominin, Denisova. Importantly, Pääbo also found that gene transfer had occurred from these now extinct hominins to Homo sapiens following the migration out of Africa around 70,000 years ago. This ancient flow of genes to present-day humans has physiological relevance today, for example affecting how our immune system reacts to infections.通过他的开创性研究,斯万特-派博完成了看似不可能的事情:对尼安德特人的基因组进行了测序,尼安德特人是当今人类的一个灭绝性亲戚。他还轰动性地发现了一个以前不为人知的人种–丹尼索瓦。重要的是,Pääbo还发现,在大约7万年前从非洲迁出后,基因从这些现已灭绝的人种转移到智人身上。这种古老的基因流向现今的人类,在今天具有生理上的意义,例如影响我们的免疫系统对感染的反应。

Pääbo’s seminal research gave rise to an entirely new scientific discipline; paleogenomics. By revealing genetic differences that distinguish all living humans from extinct hominins, his discoveries provide the basis for exploring what makes us uniquely human.派博的开创性研究催生了一门全新的科学学科:古基因组学。通过揭示区分所有活人和已灭绝人种的基因差异,他的发现为探索什么使我们成为独特的人类提供了基础。

Where do we come from?我们从哪里来?

The question of our origin and what makes us unique has engaged humanity since ancient times. Paleontology and archeology are important for studies of human evolution. Research provided evidence that the anatomically modern human, Homo sapiens, first appeared in Africa approximately 300,000 years ago, while our closest known relatives, Neanderthals, developed outside Africa and populated Europe and Western Asia from around 400,000 years until 30,000 years ago, at which point they went extinct. About 70,000 years ago, groups of Homo sapiens migrated from Africa to the Middle East and, from there they spread to the rest of the world. Homo sapiens and Neanderthals thus coexisted in large parts of Eurasia for tens of thousands of years. But what do we know about our relationship with the extinct Neanderthals? Clues might be derived from genomic information. By the end of the 1990’s, almost the entire human genome had been sequenced. This was a considerable accomplishment, which allowed subsequent studies of the genetic relationship between different human populations. However, studies of the relationship between present-day humans and the extinct Neanderthals would require the sequencing of genomic DNA recovered from archaic specimens.自古以来,我们的起源和什么使我们独特的问题一直吸引着人类。古生物学和考古学对人类进化的研究非常重要。研究提供的证据表明,解剖学上的现代人,即智人,最早出现在大约30万年前的非洲,而我们已知的最接近的亲属,尼安德特人,在非洲以外的地方发展起来,从大约40万年前到3万年前在欧洲和西亚居住,在那时候他们已经灭绝了。大约7万年前,智人群体从非洲迁移到中东,并从那里扩散到世界其他地区。  因此,智人和尼安德特人在欧亚大陆的大部分地区共存了数万年。但是我们对我们与已灭绝的尼安德特人的关系了解多少呢?线索可能来自于基因组信息。到20世纪90年代末,几乎整个人类基因组都已被测序。这是一个相当大的成就,这使得后来对不同人类种群之间的遗传关系进行了研究。然而,对现今人类和已灭绝的尼安德特人之间关系的研究将需要对从古人标本中提取的基因组DNA进行测序。

A seemingly impossible task一个看似不可能的任务

Early in his career, Svante Pääbo became fascinated by the possibility of utilizing modern genetic methods to study the DNA of Neanderthals. However, he soon realized the extreme technical challenges, because with time DNA becomes chemically modified and degrades into short fragments. After thousands of years, only trace amounts of DNA are left, and what remains is massively contaminated with DNA from bacteria and contemporary humans (Figure 1). As a postdoctoral student with Allan Wilson, a pioneer in the field of evolutionary biology, Pääbo started to develop methods to study DNA from Neanderthals, an endeavor that lasted several decades.在其职业生涯的早期,斯万特-派博对利用现代遗传学方法研究尼安德特人的DNA的可能性着迷。然而,他很快就意识到了极端的技术挑战,因为随着时间的推移,DNA会发生化学变化并降解为短小的片段。几千年后,只剩下微量的DNA,而剩下的DNA被细菌和当代人的DNA大量污染(图1)。作为进化生物学领域的先驱艾伦-威尔逊的博士后学生,派博开始开发研究尼安德特人的DNA的方法,这一努力持续了几十年。

Ancient DNA
Figure 1. DNA is localized in two different compartments in the cell. Nuclear DNA harbors most of the genetic information, while the much smaller mitochondrial genome is present in thousands of copies. After death, DNA is degraded over time and ultimately only small amounts remain. It also becomes contaminated with DNA from e.g. bacteria and contemporary humans.图1. DNA在细胞中定位在两个不同的隔间。核DNA藏有大部分的遗传信息,而小得多的线粒体基因组则有数千个拷贝。死亡后,DNA会随着时间的推移而被降解,最终只剩下少量的。它也会被诸如细菌和当代人类的DNA所污染。

In 1990, Pääbo was recruited to University of Munich, where, as a newly appointed Professor, he continued his work on archaic DNA. He decided to analyze DNA from Neanderthal mitochondria – organelles in cells that contain their own DNA. The mitochondrial genome is small and contains only a fraction of the genetic information in the cell, but it is present in thousands of copies, increasing the chance of success. With his refined methods, Pääbo managed to sequence a region of mitochondrial DNA from a 40,000-year-old piece of bone. Thus, for the first time, we had access to a sequence from an extinct relative. Comparisons with contemporary humans and chimpanzees demonstrated that Neanderthals were genetically distinct.1990年,Pääbo被招聘到慕尼黑大学,作为一名新任命的教授,他继续从事古人类DNA的研究。他决定分析尼安德特人线粒体的DNA–细胞中含有自己DNA的细胞器。线粒体的基因组很小,只包含细胞中遗传信息的一小部分,但它有成千上万的拷贝,增加了成功的机会。通过他精炼的方法,Pääbo成功地对一块4万年前的骨头上的线粒体DNA区域进行了排序。因此,我们第一次获得了一个已灭绝亲属的序列。与当代人类和黑猩猩的比较表明,尼安德特人在遗传上是与众不同的。

Sequencing the Neanderthal genome尼安德特人基因组的测序

As analyses of the small mitochondrial genome gave only limited information, Pääbo now took on the enormous challenge of sequencing the Neanderthal nuclear genome. At this time, he was offered the chance to establish a Max Planck Institute in Leipzig, Germany. At the new Institute, Pääbo and his team steadily improved the methods to isolate and analyze DNA from archaic bone remains. The research team exploited new technical developments, which made sequencing of DNA highly efficient. Pääbo also engaged several critical collaborators with expertise on population genetics and advanced sequence analyses. His efforts were successful. Pääbo accomplished the seemingly impossible and could publish the first Neanderthal genome sequence in 2010. Comparative analyses demonstrated that the most recent common ancestor of Neanderthals and Homo sapiens lived around 800,000 years ago.由于对小型线粒体基因组的分析只提供了有限的信息,派博现在承担了对尼安德特人核基因组进行测序的巨大挑战。在这个时候,他得到了在德国莱比锡建立马克斯-普朗克研究所的机会。在新的研究所里,Pääbo和他的团队稳步改进了从古人骨骸中分离和分析DNA的方法。研究小组利用新的技术发展,使DNA的测序变得非常有效。  派博还聘请了几个在群体遗传学和高级序列分析方面有专长的关键合作者。他的努力是成功的。  派博完成了看似不可能的任务,并能在2010年公布第一个尼安德特人基因组序列。比较分析表明,尼安德特人和智人的最近共同祖先生活在大约80万年前。

Map
Figure 2. A. Pääbo extracted DNA from bone specimens from extinct hominins. He first obtained a bone fragment from Neandertal in Germany, the site that gave name to the Neanderthals. Later, he used a finger bone from the Denisova Cave in southern Siberia, the site that gave name to Denisovans. B. Phylogenetic tree showing the evolution and relationship between Homo sapiens and the extinct hominins. The phylogenetic tree also illustrates the gene flows discovered by Pääbo.图2. A. Pääbo从已灭绝的人的骨骼标本中提取了DNA。他首先从德国的尼安德特人那里获得了一块骨头碎片,该遗址为尼安德特人命名。后来,他使用了来自西伯利亚南部Denisova洞的一块指骨,该遗址为丹尼索瓦人命名。B. 系统发育树显示了智人和已灭绝的人种之间的进化和关系。系统发育树也说明了派博所发现的基因流。

Pääbo and his co-workers could now investigate the relationship between Neanderthals and modern-day humans from different parts of the world. Comparative analyses showed that DNA sequences from Neanderthals were more similar to sequences from contemporary humans originating from Europe or Asia than to contemporary humans originating from Africa. This means that Neanderthals and Homo sapiens interbred during their millennia of coexistence. In modern day humans with European or Asian descent, approximately 1-4% of the genome originates from the Neanderthals (Figure 2).Pääbo和他的同事们现在可以研究尼安德特人和来自世界不同地区的现代人之间的关系。比较分析表明,尼安德特人的DNA序列与源自欧洲或亚洲的当代人类的序列相比,与源自非洲的当代人类更为相似。这意味着尼安德特人和智人在他们几千年的共存过程中进行了交配。在具有欧洲或亚洲血统的现代人中,大约有1-4%的基因组源自尼安德特人(图2)。

A sensational discovery: Denisova一个耸人听闻的发现。德尼索瓦

In 2008, a 40,000-year-old fragment from a finger bone was discovered in the Denisova cave in the southern part of Siberia. The bone contained exceptionally well-preserved DNA, which Pääbo’s team sequenced. The results caused a sensation: the DNA sequence was unique when compared to all known sequences from Neanderthals and present-day humans. Pääbo had discovered a previously unknown hominin, which was given the name Denisova. Comparisons with sequences from contemporary humans from different parts of the world showed that gene flow had also occurred between Denisova and Homo sapiens. This relationship was first seen in populations in Melanesia and other parts of South East Asia, where individuals carry up to 6% Denisova DNA.2008年,在西伯利亚南部的德尼索瓦洞穴中发现了一块4万年前的指骨碎片。这块骨头含有保存得特别好的DNA,Pääbo的团队对其进行了测序。结果引起了轰动:与尼安德特人和现今人类的所有已知序列相比,该DNA序列是独一无二的。  Pääbo发现了一个以前不为人知的人类,它被命名为Denisova。与来自世界不同地区的当代人类的序列进行比较表明,Denisova和智人之间也发生了基因流动。这种关系首先出现在美拉尼西亚和东南亚其他地区的人群中,那里的个体携带高达6%的Denisova DNA。

Pääbo’s discoveries have generated new understanding of our evolutionary history. At the time when Homo sapiens migrated out of Africa, at least two extinct hominin populations inhabited Eurasia. Neanderthals lived in western Eurasia, whereas Denisovans populated the eastern parts of the continent. During the expansionof Homo sapiens outside Africa and their migration east, they not only encountered and interbred with Neanderthals, but also with Denisovans (Figure 3).派博的发现使人们对我们的进化史有了新的认识。在智人移出非洲的时候,至少有两个已经灭绝的人类种群居住在欧亚大陆。尼安德特人生活在欧亚大陆西部,而丹尼索瓦人则居住在该大陆的东部地区。在智人向非洲以外扩张和向东迁移的过程中,他们不仅遇到了尼安德特人,而且还与丹尼索瓦人交配(图3)。

Paleogenomics and its relevance古基因组学及其相关性

Through his groundbreaking research, Svante Pääbo established an entirely new scientific discipline, paleogenomics. Following the initial discoveries, his group has completed analyses of several additional genome sequences from extinct hominins. Pääbo’s discoveries have established a unique resource, which is utilized extensively by the scientific community to better understand human evolution and migration. New powerful methods for sequence analysis indicate that archaic hominins may also have mixed with Homo sapiens in Africa. However, no genomes from extinct hominins in Africa have yet been sequenced due to accelerated degradation of archaic DNA in tropical climates.通过他的开创性研究,斯万特-派博建立了一门全新的科学学科–古基因组学。在最初的发现之后,他的小组已经完成了对另外几个已灭绝人种的基因组序列的分析。  Päbo的发现建立了一个独特的资源,被科学界广泛利用来更好地理解人类的进化和迁移。新的强大的序列分析方法表明,古人类也可能在非洲与智人混合。然而,由于热带气候下古人类DNA的加速降解,目前还没有对非洲已灭绝的人的基因组进行测序。

Thanks to Svante Pääbo’s discoveries, we now understand that archaic gene sequences from our extinct relatives influence the physiology of present-day humans. One such example is the Denisovan version of the gene EPAS1, which confers an advantage for survival at high altitude and is common among present-day Tibetans. Other examples are Neanderthal genes that affect our immune response to different types of infections.由于Svante Pääbo的发现,我们现在了解到,来自我们已灭绝的亲属的古老基因序列影响了现今人类的生理学。其中一个例子是丹尼索瓦人版本的基因EPAS1,它赋予了在高海拔地区生存的优势,在今天的西藏人中很常见。其他的例子是尼安德特人的基因影响我们对不同类型感染的免疫反应。

Pääbo's discoveries
Figure 3. Pääbo’s discoveries have provided important information on how the world was populated at the time when Homo sapiens migrated out of Africa and spread to the rest of the world. Neanderthals lived in the west and Denisovans in the east on the Eurasian continent. Interbreeding occurred when Homo sapiens spread across the continent, leaving traces that remain in our DNA.图3. 派博的发现为智人迁出非洲并传播到世界其他地区时的世界人口情况提供了重要信息。尼安德特人居住在西部,丹尼索瓦人居住在东部的欧亚大陆。当智人在大陆上传播时发生了杂交,留下了留在我们DNA中的痕迹。

What makes us uniquely human?是什么使我们成为独特的人类?

Homo sapiens is characterized by its unique capacity to create complex cultures, advanced innovations and figurative art, as well as by the ability to cross open water and spread to all parts of our planet (Figure 4). Neanderthals also lived in groups and had big brains (Figure 4). They also utilized tools, but these developed very little during hundreds of thousands of years. The genetic differences between Homo sapiens and our closest extinct relatives were unknown until they were identified through Pääbo’s seminal work. Intense ongoing research focuses on analyzing the functional implications of these differences with the ultimate goal of explaining what makes us uniquely human.智人的特点是具有创造复杂文化、先进创新和具象艺术的独特能力,以及跨越开阔水域并传播到我们星球所有地方的能力(图4)。尼安德特人也是群居的,并且有大脑袋(图4)。他们也使用工具,但在几十万年的时间里,这些工具的发展非常缓慢。智人和我们最亲近的灭绝亲属之间的基因差异一直不为人知,直到通过派博的开创性工作才得以确认。正在进行的密集研究集中于分析这些差异的功能影响,最终目的是解释是什么使我们成为独特的人类。

Denisova, Neanderthal and H. sapiens
Figure 4. Pääbo’s seminal work provides a basis for explaining what makes us uniquely human.图4. 派博的开创性工作为解释什么使我们成为独特的人类提供了一个基础。

Key publications主要出版物

Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Pääbo S. Neandertal DNA sequences and the origin of modern humans. Cell. 1997:90:19-30.Krings M, Stone A, Schmitz RW, Krainitzki H, Stoneking M, Pääbo S. Neandertal DNA序列和现代人类的起源。  细胞》。1997:90:19-30.

Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Ž, Gušic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M, Fortea J, Rosas A, Schmitz RW, Johnson PLF, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S. A draft sequence of the Neandertal genome. Science. 2010:328:710-722.Green RE, Krause J, Briggs AW, Maricic T, Stenzel U, Kircher M, Patterson N, Li H, Zhai W, Fritz MH, Hansen NF, Durand EY, Malaspinas AS, Jensen JD, Marques-Bonet T, Alkan C, Prüfer K, Meyer M, Burbano HA, Good JM, Schultz R, Aximu-Petri A, Butthof A, Höber B, Höffner B, Siegemund M, Weihmann A, Nusbaum C, Lander ES, Russ C, Novod N, Affourtit J, Egholm M, Verna C, Rudan P, Brajkovic D, Kucan Ž, Gušic I, Doronichev VB, Golovanova LV, Lalueza-Fox C, de la Rasilla M.Fortea J, Rosas A, Schmitz RW, Johnson PLF, Eichler EE, Falush D, Birney E, Mullikin JC, Slatkin M, Nielsen R, Kelso J, Lachmann M, Reich D, Pääbo S. 尼安德特人基因组的序列草案。  科学》。2010:328:710-722.

Krause J, Fu Q, Good JM, Viola B, Shunkov MV, Derevianko AP, Pääbo S. The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature. 2010:464:894-897.Krause J, Fu Q, Good JM, Viola B, Shunkov MV, Derevianko AP, Pääbo S. 西伯利亚南部未知人种的完整线粒体DNA基因组。  自然》。2010:464:894-897.

Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PL, Maricic T, Good JM, Marques-Bonet T, Alkan C, Fu Q, Mallick S, Li H, Meyer M, Eichler EE, Stoneking M, Richards M, Talamo S, Shunkov MV, Derevianko AP, Hublin JJ, Kelso J, Slatkin M, Pääbo S. Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature. 2010:468:1053-1060.Reich D, Green RE, Kircher M, Krause J, Patterson N, Durand EY, Viola B, Briggs AW, Stenzel U, Johnson PL, Maricic T, Good JM, Marques-Bonet T, Alkan C, Fu Q, Mallick S, Li H, Meyer M, Eichler EE, Stoneking M, Richards M, Talamo S, Shunkov MV, Derevianko AP, Hublin JJ, Kelso J, Slatkin M, Pääbo S。来自西伯利亚Denisova洞的一个古人类群体的遗传历史。  自然》。2010:468:1053-1060.

Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prüfer K, de Filippo C, Sudmant PH, Alkan C, Fu Q, Do R, Rohland N, Tandon A, Siebauer M, Green RE, Bryc K, Briggs AW, Stenzel U, Dabney J, Shendure J, Kitzman J, Hammer MF, Shunkov MV, Derevianko AP, Patterson N, Andrés AM, Eichler EE, Slatkin M, Reich D, Kelso J, Pääbo S. A high-coverage genome sequence from an archaic Denisovan individual. Science. 2012:338:222-226.Meyer M, Kircher M, Gansauge MT, Li H, Racimo F, Mallick S, Schraiber JG, Jay F, Prüfer K, de Filippo C, Sudmant PH, Alkan C, Fu Q, Do R, Rohland N, Tandon A, Siebauer M, Green RE, Bryc K, Briggs AW, Stenzel U, Dabney J, Shendure J, Kitzman J, Hammer MF, Shunkov MV, Derevianko AP, Patterson N, Andrés AM, Eichler EE, Slatkin M, Reich D, Kelso J, Pääbo S.  来自一个古老的丹尼索瓦人个体的高覆盖率基因组序列。  科学》。2012:338:222-226.

Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, Heinze A, Renaud G, Sudmant PH, de Filippo C, Li H, Mallick S, Dannemann M, Fu Q, Kircher M, Kuhlwilm M, Lachmann M, Meyer M, Ongyerth M, Siebauer M, Theunert C, Tandon A, Moorjani P, Pickrell J, Mullikin JC, Vohr SH, Green RE, Hellmann I, Johnson PL, Blanche H, Cann H, Kitzman JO, Shendure J, Eichler EE, Lein ES, Bakken TE, Golovanova LV, Doronichev VB, Shunkov MV, Derevianko AP, Viola B, Slatkin M, Reich D, Kelso J, Pääbo S. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature. 2014:505: 43-49.Prüfer K, Racimo F, Patterson N, Jay F, Sankararaman S, Sawyer S, Heinze A, Renaud G, Sudmant PH, de Filippo C, Li H, Mallick S, Dannemann M, Fu Q, Kircher M, Kuhlwilm M, Lachmann M, Meyer M, Ongyerth M, Siebauer M, Theunert C, Tandon A, Moorjani P, Pickrell J, Mullikin JC, Vohr SH, Green RE, Hellmann I, Johnson PL, Blanche H, Cann H, Kitzman JO, Shendure J, Eichler EE, Lein ES, Bakken TE, Golovanova LV, Doronichev VB, Shunkov MV, Derevianko AP, Viola B, Slatkin M, Reich D, Kelso J, Pääbo S。阿尔泰山尼安德特人的完整基因组序列。  自然》杂志。2014:505: 43-49.

>Svante Pääbo was born 1955 in Stockholm, Sweden. He defended his PhD thesis in 1986 at Uppsala University and was a postdoctoral fellow at University of Zürich, Switzerland and later at University of California, Berkeley, USA. He became Professor at the University of Munich, Germany in 1990. In 1999 he founded the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany where he is still active. He also holds a position as adjunct Professor at Okinawa Institute of Science and Technology, Japan.>斯万特-派博1955年出生于瑞典的斯德哥尔摩。1986年在乌普萨拉大学通过博士论文答辩,曾在瑞士苏黎世大学和美国加州大学伯克利分校做博士后研究。1990年,他成为德国慕尼黑大学的教授。1999年,他在德国莱比锡成立了马克斯-普朗克进化人类学研究所,目前仍在那里工作。他还在日本的冲绳科学技术学院担任兼职教授的职务。

Illustrations: © The Nobel Committee for Physiology or Medicine. Illustrator: Mattias Karlén插图:© 诺贝尔生理学或医学委员会。插画师。马蒂亚斯-卡伦


The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of humankind.诺贝尔大会由卡罗林斯卡学院的50名教授组成,负责颁发诺贝尔生理学或医学奖。其诺贝尔委员会对提名进行评估。自1901年以来,诺贝尔奖一直颁发给那些为人类利益做出最重要发现的科学家。

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