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\"What can we learn from the genes of our closest evolutionary relatives? Neanderthal Man tells the story of geneticist Svante Pääbo's mission to answer that question, beginning with the study of DNA in Egyptian mummies in the early 1980s and culminating in his sequencing of the Neanderthal genome in 2009. From Pääbo, we learn how Neanderthal genes offer a unique window into the lives of our hominin relatives and may hold the key to unlocking the mystery of why humans survived while Neanderthals went extinct. Drawing on genetic and fossil clues, Pääbo explores what is known about the origin of modern humans and their relationship to the Neanderthals and describes the fierce debate surrounding the nature of the two species' interactions. A riveting story about a visionary researcher and the nature of scientific inquiry, Neanderthal Man offers rich insight into the fundamental question of who we are\"-- Provided by publisher.

\"What can we learn from the genes of our closest evolutionary relatives? Neanderthal Man tells the story of geneticist Svante P�a�abo's mission to answer that question, beginning with the study of DNA in Egyptian mummies in the early 1980s and culminating in his sequencing of the Neanderthal genome in 2009. From P�a�abo, we learn how Neanderthal genes offer a unique window into the lives of our hominin relatives and may hold the key to unlocking the mystery of why humans survived while Neanderthals went extinct. Drawing on genetic and fossil clues, P�a�abo explores what is known about the origin of modern humans and their relationship to the Neanderthals and describes the fierce debate surrounding the nature of the two species' interactions. A riveting story about a visionary researcher and the nature of scientific inquiry, Neanderthal Man offers rich insight into the fundamental question of who we are\"-- Provided by publisher.

A recent genetic association study 1 identified a gene cluster on chromosome 3 as a risk locus for respiratory failure after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A separate study (COVID-19 Host Genetics Initiative) 2 comprising 3,199 hospitalized patients with coronavirus disease 2019 (COVID-19) and control individuals showed that this cluster is the major genetic risk factor for severe symptoms after SARS-CoV-2 infection and hospitalization. Here we show that the risk is conferred by a genomic segment of around 50 kilobases in size that is inherited from Neanderthals and is carried by around 50% of people in south Asia and around 16% of people in Europe. Risk of severe COVID-19 is conferred by a genomic segment that is inherited from Neanderthals and is carried by around 50% and 16% of people in south Asia and Europe, respectively.

\"What if all our legends are true? A rousing, fast-paced novel of time travel unlike any other, from acclaimed author Wil McCarthy. What if our legends are older than we think? All the Stone Age has left behind are rocks and bones; all other materials have rotted away, leaving no trace. But what if \"cave men\" never existed, and the Stone Age was a time of great sophistication still preserved in our oldest stories? In a brilliant and dangerous brain hacking experiment, Harv Leonel and Tara Mukherjee are about to discover entire lifetimes of human memory coded in our genes, and reveal ancient legends - from knights and trolls, to flood myths, to the birth of humanity itself - that are as real as they are deadly. Before disaster erased the coastlines and river valleys of the Antediluvian age--before the Flood--men and women struggled and yearned and innovated in a world of savage contrasts into which Harv and Tara are thrust, unprepared. Will their science be enough to save them?\"-- Provided by publisher.

In the modern human genome, elevated Neanderthal ancestry is found at genes affecting keratin filaments, suggesting that gene flow with Neanderthals helped modern humans to adapt to non-African environments; deficiencies of Neanderthal ancestry are also found, particularly on the X chromosome and in genes expressed highly in testes, suggesting that some Neanderthal mutations were not tolerated on a modern human genetic background as they reduced male fertility. Neanderthal genes today The modern human genome contains traces of Neanderthal ancestry. But is Neanderthal DNA distributed uniformly across the human genome, or is it concentrated more in some parts than in others? Sriram Sankararaman et al . show that parts of the human genome enriched for genes affecting keratin filaments (in hair, for example) also contain a relatively high concentration of Neanderthal DNA, suggesting that this DNA helped modern humans adapt to the chillier non-African environment. On the downside, many Neanderthal-derived alleles are associated with disease risk. Other parts of the human genome contain a deficiency of Neanderthal alleles, implying their active removal in evolution. Among the 'lost' genes are a number expressed in the testis and on the X chromosome, implying that Neanderthal DNA reduced human fertility when moved to a modern human genetic background. Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture 1 , 2 . The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci 1 , 3 , 4 , 5 , 6 , 7 , 8 . We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans 9 . Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes 10 , 11 , 12 . These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

We present a high-quality genome sequence of a Neanderthal woman from Siberia. We show that her parents were related at the level of half-siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neanderthal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neanderthals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high-quality Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans. A complete genome sequence is presented of a female Neanderthal from Siberia, providing information about interbreeding between close relatives and uncovering gene flow events among Neanderthals, Denisovans and early modern humans, as well as establishing substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans. Genome sequence of Neanderthal woman Recent excavations in the Denisova Cave in the Altai Mountains of southern Siberia have yielded a wealth of hominin fossils from a site that has been occupied for perhaps 250,000 years or more. Now a high-quality genome sequence has been determined from a circa 50,000-year-old toe bone — a proximal toe phalanx — excavated from the east gallery of Denisova Cave in 2010. The sequence is that of a Neanderthal woman whose parents were closely related — perhaps half-siblings or uncle and niece. Such inbreeding was also common among her recent ancestors. Comparisons with other archaic and present-day human genomes reveal several gene-flow events among Neanderthals, the closely related Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. The high-quality Neanderthal genome also helps to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

Human genes governing innate immunity provide a valuable tool for the study of the selective pressure imposed by microorganisms on host genomes. A comprehensive, genome-wide study of how selective constraints and adaptations have driven the evolution of innate immunity genes is missing. Using full-genome sequence variation from the 1000 Genomes Project, we first show that innate immunity genes have globally evolved under stronger purifying selection than the remainder of protein-coding genes. We identify a gene set under the strongest selective constraints, mutations in which are likely to predispose individuals to life-threatening disease, as illustrated by STAT1 and TRAF3. We then evaluate the occurrence of local adaptation and detect 57 high-scoring signals of positive selection at innate immunity genes, variation in which has been associated with susceptibility to common infectious or autoimmune diseases. Furthermore, we show that most adaptations targeting coding variation have occurred in the last 6,000-13,000 years, the period at which populations shifted from hunting and gathering to farming. Finally, we show that innate immunity genes present higher Neandertal introgression than the remainder of the coding genome. Notably, among the genes presenting the highest Neandertal ancestry, we find the TLR6-TLR1-TLR10 cluster, which also contains functional adaptive variation in Europeans. This study identifies highly constrained genes that fulfill essential, non-redundant functions in host survival and reveals others that are more permissive to change-containing variation acquired from archaic hominins or adaptive variants in specific populations-improving our understanding of the relative biological importance of innate immunity pathways in natural conditions.

Genetic similarity among late Neanderthals is predicted well by their geographical location, and although some of these Neanderthals were contemporaneous with early modern humans, their genomes show no evidence of recent gene flow from modern humans. Late Neanderthal relations Many questions remain about the relationship between populations of Neanderthals around the time of their final interactions with modern humans, and how this contributed to the evolution of modern humans. Janet Kelso, Svante Pääbo and colleagues sequenced the genomes of five Neanderthals that lived between 39,000 and 47,000 years ago, broadening the temporal and geographical range of available Neanderthal genomes. They analyse these genomes together with previously sequenced ancient genomes and find that relatedness among Neanderthals is related to geographic proximity. They find that the majority of gene flow into early modern humans originated from one or more Neanderthal populations that diverged from the late Neanderthals at least 70,000 years ago, but after their split from the Altai Neanderthal approximately 150,000 years ago. Although it has previously been shown that Neanderthals contributed DNA to modern humans 1 , 2 , not much is known about the genetic diversity of Neanderthals or the relationship between late Neanderthal populations at the time at which their last interactions with early modern humans occurred and before they eventually disappeared. Our ability to retrieve DNA from a larger number of Neanderthal individuals has been limited by poor preservation of endogenous DNA 3 and contamination of Neanderthal skeletal remains by large amounts of microbial and present-day human DNA 3 , 4 , 5 . Here we use hypochlorite treatment 6 of as little as 9 mg of bone or tooth powder to generate between 1- and 2.7-fold genomic coverage of five Neanderthals who lived around 39,000 to 47,000 years ago (that is, late Neanderthals), thereby doubling the number of Neanderthals for which genome sequences are available. Genetic similarity among late Neanderthals is well predicted by their geographical location, and comparison to the genome of an older Neanderthal from the Caucasus 2 , 7 indicates that a population turnover is likely to have occurred, either in the Caucasus or throughout Europe, towards the end of Neanderthal history. We find that the bulk of Neanderthal gene flow into early modern humans originated from one or more source populations that diverged from the Neanderthals that were studied here at least 70,000 years ago, but after they split from a previously sequenced Neanderthal from Siberia 2 around 150,000 years ago. Although four of the Neanderthals studied here post-date the putative arrival of early modern humans into Europe, we do not detect any recent gene flow from early modern humans in their ancestry.

It is known that there was gene flow from Neanderthals to modern humans around 50,000 years ago; now, analysis of a Neanderthal genome from the Altai Mountains in Siberia reveals evidence of gene flow 100,000 years ago in the other direction—from early modern humans to Neanderthals. Early gene exchange between modern humans and Neanderthals Sergi Castellano and colleagues analyse genomic data from Neanderthal and Denisovan modern humans from the Altai Mountains in Siberia and from Neanderthals from Spain and Croatia. Using a Bayesian method for inference of demographic models known as G-PhoCS (Generalized Phylogenetic Coalescent Sampler), the authors obtain preliminary quantitative estimates of previously reported gene flow events between modern and archaic humans. They also report evidence of gene flow from an early modern human population to the ancestors of Neanderthals from the Altai Mountains more than 100,000 years ago, in the opposite direction to the instances of gene flow from Neanderthals to modern humans. It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.