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The Derived FOXP2 Variant of Modern Humans was Shared with Neandertals
Abstract
Although many animals communicate vocally, no extant creature rivals modern humans in language ability. Therefore, knowing when and under what evolutionary pressures our capacity for language evolved is of great interest. Here, we find that our closest extinct relatives, the Neandertals, share with modern humans two evolutionary changes in FOXP2, a gene that has been implicated in the development of speech and language. We furthermore find that in Neandertals, these changes lie on the common modern human haplotype, which previously was shown to have been subject to a selective sweep. These results suggest that these genetic changes and the selective sweep predate the common ancestor (which existed about 300,000-400,000 years ago) of modern human and Neandertal populations. This is in contrast to more recent age estimates of the selective sweep based on extant human diversity data. Thus, these results illustrate the usefulness of retrieving direct genetic information from ancient remains for understanding recent human evolution.
... The Dikika australopithecine infant's hyoid bone (Alemseged et al. 2006) and the detection of the FOXP2 'language gene' on chromosome 7 from 'Neanderthal' remains (cf. Enard et al. 2002a;Zhang et al. 2002;Sanjuan et al. 2006;Krause et al. 2007) render these discussions superfluous. The major syntheses of recent decades about language origins tend to return to linguistic gradualist perspectives (Bickerton 1990(Bickerton , 1993(Bickerton , 1996(Bickerton , 2010Dunbar 1996;Aitchison 1996;Falk 2009), and their authors arrive at the same basic finding: human language is such a complex phenomenon that its evolution, in every sense, demands a very lengthy process, dating back millions of years. ...
... For instance, the planum temporale, presenting a left-right asymmetry favouring the left (Geschwind and Levitsky 1968), which has been related to language reception, is also present in apes (Gannon et al. 1998(Gannon et al. , 2001. Moreover, the detection of the FOXP2 gene on chromosome 7 of Robusts (Krause et al. 2007;cf. Enard et al. 2002a;Zhang et al. 2002;Sanjuan et al. 2006) but the absence of such schizophrenia susceptibility alleles as NRG3 in them refutes the idea (in fact schizophrenia may have appeared much later than Graziles; Bednarik and Helvenston 2011). ...
Among the many generic explanations offered over the past two centuries for rock art production, those involving several brain illnesses and shamanism are selected for detailed analysis. These proposals are reviewed in light of the aetiologies of the psychiatric conditions linked to rock art. Some are related to the assumption that palaeoart was introduced through shamanism. Although no simplistic link between shamanism and brain disorders has been demonstrated, relevant susceptibility alleles might be involved in some shamanic experiences. No connection between rock art and shamanism has been credibly demonstrated to date. Moreover, the assumption that neuropathologies and shamanism preceded the advent of palaeoart also appears to be mistaken. It derives from the belief that palaeoart was introduced by 'anatomically modern humans' and on the discredited replacement hypothesis. These interlinked issues are discussed.
... [61][62][63] But soon after, analysis of Neandertal DNA verified that our closest relative already shared with modern humans these two evolutionary changes in FOXP2. 64 The result suggested that the two amino-acid substitutions had occurred 400 thousand years ago or even before in a common ancestor of modern humans and Neandertals. 63,64 This relevant finding, once excluded the possibility of inbreeding, showed that language (if normal human FOXP2 gene is the precondition for language development) could be present in other members of the genus Homo. ...
... 64 The result suggested that the two amino-acid substitutions had occurred 400 thousand years ago or even before in a common ancestor of modern humans and Neandertals. 63,64 This relevant finding, once excluded the possibility of inbreeding, showed that language (if normal human FOXP2 gene is the precondition for language development) could be present in other members of the genus Homo. There are controversies about the possibility that Neandertals shared with us something like modern language. ...
This review is based on a conference presented in June 2023. Its main objective is to explain the cognitive differences between humans and non-human primates (NHPs) focusing on characteristics of their brains. It is based on the opinion of a clinical neurologist and does not intend to go beyond an overview of this complex topic. As language is the main characteristic differentiating humans from NHPs, this review is targeted at their brain networks related to language. NHPs have rudimentary forms of language, including primitive lexical/semantic signs. Humans have a much broader lexical/semantic repertory, but syntax is the most important characteristic, which is probably unique to Homo sapiens. Angular gyrus, Broca's area, temporopolar areas, and arcuate fascicle, are much more developed in humans. These differences may explain why NHPs did not develop a similar language to ours. Language had a profound influence on all other higher nervous activities.
... Based on archeological evidence, such as the structure of the hyoid bone, the flexion of the bones of the skull base, increased voluntary control of the muscles of the diaphragm, and anatomy of external and middle ear, as well as the observation that FOXP2 genetic modifications predated the human-Neanderthals split 37,38 , most paleoanthropologists conclude that the speech apparatus experienced significant development starting from about two million years ago (ya) and that it reached modern or nearly modern configurations before 600,000 ya [39][40][41] . Thus, archeological evidence of the speech apparatus evolution puts the following constrains on the receptive-expressive phenotypes evolution: 1) the command-language-comprehension with no expressive-language-phenotypebefore 2 million ya; ...
Use of syntactic language is a unique characteristic of humans. Following the split of human line from chimpanzee line around six million years ago some individuals acquired genetic modifications that enabled certain linguistic abilities. Over time these mutations were fixed in the human population and currently enable modern human syntactic communication. Inevitably, in some modern individuals, language-critical genes regress to their ancestral functionality causing partial loss of language abilities. Population studies of individuals with language deficits reveal language phenotypes that may correspond to stages of language evolution. Previously, we discovered three distinct language-comprehension-phenotypes: 1) individuals in the command-language-comprehension-phenotype were limited to comprehension of simple commands; 2) the modifier-language-comprehension-phenotype showed additional comprehension of color, size, and number modifiers; 3) the most-advanced syntactic-language-comprehension-phenotype added comprehension of complex grammatical sentences ¹ . In this study we clustered language comprehension skills together with speech abilities in 55,000 individuals-with-language-deficits. We discovered four distinct phenotypes: 1) command-language-comprehension with no-expressive-language; 2) modifier-language-comprehension with single-word-expressive-language; 3) modifier-language-comprehension with single-sentence-expressive-language; 4) syntactic-language-comprehension with multi-sentence-expressive-language. These phenotypes may align with four distinct stages of language comprehension and speech co-evolution. Using homology between neurological mechanisms underlying language and stone-tools-manufacturing we deduce the chronology of language acquisition in our ancestors.
... Human FOXP2 has incorporated two fixed amino acid changes in a broadly defined transcription suppression domain (Zhang et al., 2002). These two amino acid changes (N325S, T303N) occurred at some point since the evolutionary split from the lineage of chimpanzees and bonobos (Enard et al., 2002) and were likely present before the split of Neanderthals and Homo sapiens (Krause et al., 2007), which is currently estimated to have happened between 800 thousand years ago and 400 thousand years ago (cf. Endicott et al., 2010;Harvati & Reyes-Centeno, 2022). ...
... En cuanto a su relación con el origen del lenguaje, Krause et al. (2007) analizaron una muestra genética perteneciente a un ejemplar de Homo neanderthalensis y descubrieron que este poseía la misma versión mutada del gen FOXP2 que el Homo sapiens. Este descubrimiento plantea, entre otras, dos cuestiones fundamentales: en primer lugar, si los neandertales poseían la misma versión mutada del gen FOXP2, entonces sería posible suponer que contaban con un desarrollo cerebral similar al actual (ya que, como apuntamos previamente, el FOXP2 está involucrado en el desarrollo neuronal de diversas regiones cerebrales con competencias lingüísticas), lo que quizá podría favorecer la presencia de una capacidad lingüística. ...
The origin of language is one of the most widely discussed topics in the field of Humanities. Fortunately, we currently have a wide range of evidence that allows us to investigate this issue empirically. Thus, the aim of this paper is to revise some of this evidence, focusing particularly on biological, anthropological and psychological data. Finally, we will try to show that, although such evidence includes disparate data about the origin of language in the genus Homo, in reality they are not incompatible and perhaps speak in favour of an early language not necessarily based on oral communication.
El origen del lenguaje es uno de los temas que, sin lugar a duda, más debate ha generado en el campo de las humanidades. Afortunadamente, en la actualidad contamos con diversos indicios que permiten analizar esta cuestión de manera empírica; así pues, el objetivo del presente trabajo será revisar algunas de estas evidencias, centrándonos, concretamente, en tres tipos: biológicas, antropológicas y psicológicas. Finalmente, intentaremos demostrar que, aunque estas evidencias puedan aportar datos dispares acerca del origen del lenguaje en el género Homo, en realidad no son incompatibles y quizá hablen a favor de un primer lenguaje no basado necesariamente en la comunicación oral.
... En este debate ha entrado la genética, mediante la detección de los alelos modernos del gen FOXP2, estrechamente relacionado con el lenguaje, en el genoma neandertal (Krause et al. 2007). No obstante, la evidencia genética no cierra el debate, sino que debe ser contrastada con los datos procedentes de otras disciplinas (Benítez y Longa, 2011). ...
RESUMEN: La Arqueología Cognitiva utiliza cons-tructos prestados de la Psicología con el fin de analizar el tipo de mente subyacente a las evidencias del registro arqueológico. En este caso se realizará un breve acerca-miento a las primeras representaciones gráficas rupes-tres paleolíticas, caracterizadas por su color rojo y au-sencia de figuración, bajo la óptica de las capacidades cognitivas de mayor protagonismo en la mente de los hu-manos modernos. Para ello se analizará la naturaleza de las capacidades primarias y su combinación en las emer-gentes, para aplicarlas a las evidencias rupestres. Como conclusión, es posible argumentar que el estilo de algu-nas representaciones está influenciado por nuestras ca-racterísticas neurobiológicas, y que las capacidades cog-nitivas necesarias para llevar a cabo las representacio-nes no figurativas más antiguas ya estarían presentes en Homo neanderthalensis. ABSTRACT: Cognitive Archaeology tends to use borrowed constructs from Psychology in order to analyze the kind of mind which underlies the archaeological record evidence. In this case, a brief approach to the earliest palaeolithic graphic cave representations, characterized by red color and figurativeness absence, will be carried out under the main cognitive capacities' perspective in the modern human mind. To this purpose it will be analyzed the nature of the primary capacities and their combination into the emergent ones, to apply them to the cave art representations. As a conclusión it is possible to support that the style of many representations is influenced by our neurobiological characteristics, and that cognitive capacities neccesary to carry out the earliest non-figurative representations were already present in Homo neanderthalensis.
... Були піддані порівняльному аналізу секвеновані частини геномів різних популяцій сучасної людини (Homo sapiens), неандертальця (Homo neanderthalensis) та людиноподібних приматів. Одним із перших резонансних висновків [21] був такий: неандертальці мають ідентичні із сучасними людьми дві амінокислотні заміни в гені FOXP2, що бере участь у розвитку мови та забезпечує його носіям суттєві адаптивні переваги. Інакше кажучи, сучасний варіант цього гена виник раніше 300 000-400 000 років тому, тобто до поділу людини та неандертальця на дві еволюційні гілки. ...
The studies of Svante Pääbo, Nobel Laureate in Physiology or Medicine in 2022 are analyzed in two aspects: firstly, as the most striking example of the evolutionary transformation of classical science into the so-called post-academic (techno)science and, secondly, as an element of the so-called "biopolitical turn" in the socio-humanitarian and political knowledge of technological civilization and, in particular, in the concept of "civil society".
... Mesmo na literatura técnica, reações de vários tipos não se fizeram esperar. O gene foi rapidamente incorporado em explicações evolutivas da linguagem, com afirmações sobre a presença da linguagem nos nossos parentes mais próximos, que também tinham a versão humana e moderna do gene (Krause et al., 2007;Reich et al., 2010), embora não existam provas que suportem este argumento. Propor explicações deste tipo requer um evelado grau de especulação e, além disso, tal como mostra Benítez-Burraco (2007) ...
This paper aims at outlining some aspects of biolinguistics — the study of the biological bases of language. After a brief introduction, some considerations are made on the reasons for the lack of attention given to this approach until very recently, as well as some reasons for its reemergence, which is now underway.
... It is unknown if Homo erectus also had the capacity for language. However, both Homo sapiens and Homo neandertalis, who evolved from H. erectus semiindependently, had the capacity for language (Krause et al., 2007). Whenever language first evolved, it may have impacted sleep patterns. ...
... Neanderthals presumably had the phonological loop, based on the Kebara 2 hyoid from Israel, ca. 63,000 years ago (Arensburg et al. 1989;D'Anastasio et al. 2013;Lieberman 1993), as well as the FOXP2 gene (Krause et al. 2007). Integration between the phonological loop and visio-spatial memory is suggested by the probable musical instrument at Divje Babe I cave, Slovenia-a hollow cave-bear femur broken at both ends, with four holes in a straight line-dating between 60,000 and 50,000 years ago (Turk and Dimkaroski 2011). ...
Scholars from a variety of disciplines consider cases of convergence in lithic technology, when functional or developmental constraints result in similar forms in independent lineages.
Hominins began using stone tools at least 2.6 million years ago, perhaps even 3.4 million years ago. Given the nearly ubiquitous use of stone tools by humans and their ancestors, the study of lithic technology offers an important line of inquiry into questions of evolution and behavior. This book examines convergence in stone tool-making, cases in which functional or developmental constraints result in similar forms in independent lineages. Identifying examples of convergence, and distinguishing convergence from divergence, refutes hypotheses that suggest physical or cultural connection between far-flung prehistoric toolmakers. Employing phylogenetic analysis and stone-tool replication, the contributors show that similarity of tools can be caused by such common constraints as the fracture properties of stone or adaptive challenges rather than such unlikely phenomena as migration of toolmakers over an Arctic ice shelf.
ContributorsR. Alexander Bentley, Briggs Buchanan, Marcelo Cardillo, Mathieu Charbonneau, Judith Charlin, Chris Clarkson, Loren G. Davis, Metin I. Eren, Peter Hiscock, Thomas A. Jennings, Steven L. Kuhn, Daniel E. Lieberman, George R. McGhee, Alex Mackay, Michael J. O'Brien, Charlotte D. Pevny, Ceri Shipton, Ashley M. Smallwood, Heather Smith, Jayne Wilkins, Samuel C. Willis, Nicolas Zayns
... So, it has long been regarded as crucial for human cognitive uniqueness. However, studies have shown that the FOXP2 gene is not unique to modern humans (Neanderthals and other animal such as some species of birds, too, have the FOXP2 gene), and there is no recent selection for it (Krause et al., 2007;Gazzaniga, Ivry, and Mangun, 2014;Atkinson et al., 2018). According to Gazzaniga, Ivry and Mangun (2014, p.503), the FOXP2 regulates a wide array of genes that are involved with e.g., morphogenesis, intracellular signalling, neuron outgrowth, and learning, etc. ...
Aesthetic phenomena have been intertwined with the life of humans to a significant degree that is not observed in non-human animals. The complexity and subtlety of it have long been regarded as one symbol of human’s exceptional cognitive power. This power can sometimes be misrepresented by a view that regards human aesthetic behaviours as innate/encoded and automated settings that are brought along with the human brain . In scenarios like this, the naturally selected brain takes up a role as some super explanator—by appealing to the configurations of the neural connectivity as reasons/causations for observed phenotypic traits. Therefore, this line of thinking can sometimes obscure the role played by the sociocultural background in affecting those configurations.
By drawing upon the notion of niche construction, I will propose a nature-nurture coevolving framework for understanding human cognitive evolution. It will be argued that the evolutionary trajectory of human cognition is heavily defined by and is, therefore, better understood through the lens of a human cultural niche and of contextualised/context-dependent expressions of human behavioural traits. This view will be delivered by highlighting the dynamics between selective pressures and the differential expression of human phenotypic traits and acknowledging the evolutionary causal role of human cultural behaviours and practices. Finally, I argue that a major evolution of social cognition was brought about through an aesthetic tradition of the Acheulean and conclude by briefly proposing a potential subject for future study.
The basic research method applied in this article is theoretical deduction. Specifically, a restricted interdisciplinary investigation that concerns academic literature from relevant fields (centring on the topic of niche construction) of archaeology, evolutionary biology and human cognition was used. Furthermore, through a process of assessing and identifying of plausible evidence, the abovementioned arguments of this study are generated.
... Humans have evolved a novel FOXP2 variant that is characterized by two fixed, nonsynonymous mutations and is associated with changes in the development and structure of the cortex, basal ganglia, and cerebellum that affects orofacial motor control (Enard et al. 2009). The derived version of FOXP2 has also been observed in Neandertals and Denisovans, indicating that certain aspects of brain plasticity important for the acquisition of speech and language may have been shared by several late hominin species (Krause et al. 2007;Meyer et al. 2012). ...
Changes in brain size and organization are key evolutionary adaptations in primates, including humans. For centuries, biological anthropologists and neuroscientists have described diversity in neuroanatomy across species while developing novel ways to study and compare brains. From these studies, we have gained insight into how primate brains differ in cellular composition, connectivity patterns and relative volumes of brain areas as well as the neuroanatomical specializations that give rise to distinct behaviors.
... They do not, however, suggest that 'full language' was present prior to modern humans and allow for the possibility that syntax, speech and vocabulary size were significantly impoverished in this common ancestor. The cross-species prevalence of the FOXP2 gene as well as evidence that suggests its (or a variant's) possible presence in Neandertals (Krause et al. 2007) also serves to challenge the uniqueness and rapidity claims of saltation views (which assumed the gene was unique to humans). Everett (2017), on the other hand, goes further to suggest that the epoch which produced full language was that of homo erectus. ...
In their recent book, Ladyman and Wiesner (What is a complex system?, Yale University Press, 2020) delineate the bounds of the exciting interdisciplinary field of complexity science. In this work, they provide examples of generally accepted complex systems and common features which these possess to varying degrees. In this paper, I plan to extend their list to include the formal study of natural language, i.e. linguistics. In fact, I will argue that language exhibits many of the hallmarks of a complex system, specifically a complex biological system. Thus, my aim is to advocate contra the the ‘Minimalist Program’ (Chomsky, The minimalist program, MIT Press, Cambridge, 1995), which motivates simple underlying mechanisms (i.e. Merge) in their idealisations, that biolinguistics should embrace a ‘Maximalist Program’ in which multiple subfields contribute component explanations to an emerging whole.
... For example: If the FOXP2 genes of pre-150 ka hominids are not identical to that of modern humans [It will reveal that H. sapiens appeared with the dual-opposite genetic potential and Neandertals differentiated from Levantine early H. sapiens. Because, Neandertal FOXP2 gene is identical to that of modern humans [15,185], and the origin of the modern FOXP2 is between 120 and 200 ka ago [16]. These data also imply that complex syntactic language appeared with H. sapiens because the modern FOXP2 geneis essential for the normal development of speech] If the 60 ka old La Quina 9 and La Ferrassie 1 comprise the genomes of the 60 ka old Northwest African humans as opposed to the earlier European Neandertals [It will demonstrate that the anatomical and behavioral modernizations of the Neandertals were triggered by the gene flow from modern subspecies, see ...
The start time of Homo sapiens is still controversial between 150 thousand and 2 million years ago. A new paradigm is requisite. If modern humans first emerged in Africa, why is the origin of anatomically modern humans statistically (design matrix) in the Levant? If modern behavior originated in Africa, why are the oldest known shell beads and the earliest known intentional burials in the Levant? Also, if Neandertals evolved from pre-Neandertals at least 250 ka (thousand years) ago, why is the most recent common mtDNA ancestor between 84.6 and 138.5 ka ago? Similarly, why is the DNA sequence divergence between the Vindija and Mezmaiskaya Neandertals about 140 ka ago? The anatomical, genetic, archaeological, bioanthropological data are best compatible with the new paradigm that pre-150 ka Homo was in reality a distinct genus, not “true human”, they went extinct and H. sapiens macroevolutionary appeared in the Levant circa 150 ka ago with new characteristics such as a dual-opposite genetic potential (both modern and archaic), early weaning, adolescent growth spurt, and also the genetic potentials of complex syntactic language, behavioral modernity and true chin.
... Decades after this initial debate, the development of research in genetics has contributed to the emergence of new research avenues on the topic. For instance, it is now possible to detect the presence of the FOXP2 gene in prehistoric populations (Krause et al. 2007;Trinkaus 2007), which, in conjunction with other candidate genes, would be implicated in language-related phenotypes (Fisher 2017) and, in this way, add to our knowledge on the emergence of language and symbolic thought. Parallel to this, growing fossil evidence supports an early evolution of speaking abilities (e.g. ...
How can we understand prehistoric lithic objects? What meaning should we give them and what view should we adopt to claim access to their significance? How can we reduce and clarify our biases? This article is a proposal to introduce Peircian semiotics to review lithic objects. For a long time, these were apprehended as types, sometimes within evolutionary lineages; however, in this research, knapped stone objects will be perceived through a semio-pragmatic grid and reviewed as signs. The proposed approach is a new way of accessing the fields of technical phenomena of prehistoric communities. This new perception aims at a quest for objectivity, by clarifying the affective, analytical and interpretative a priori as an answer to the sometimes very personal view of the prehistorian on lithic objects. Charles Sanders Peirce’s logical theory of signs or semiotics is contextualized within an ‘artisanal’ reading of prehistoric tools as initiated by Éric Boëda and further developed by Michel Lepot. Through this phaneroscopic/phenomenological vision, the technical object, now a sign-object, is placed in action (semiosis) within a system of signs. This new trajectory is positioned both as a methodological tool and as an innovative milestone in the construction of a more logical episteme in Prehistory, taking lithics both as signs of past human activity and of archaeological representations.
... У 2007 р. Сванте Пеебо показав, що неандертальці мають спільні з сучасними людьми дві еволюційні зміни в гені FOXP2, який залучений до розвитку мовлення і здатності говорити, що дозволило припустити існування у неандертальців мови [26]. ...
Нобелівську премію з фізіології або медицини у 2022 р. присуджено шведському досліднику-палеогенетику, фахівцю в галузі еволюційної генетики, директору відділу генетики Інституту еволюційної антропології імені Макса Планка в Лейпцигу (Німеччина) професору Сванте Пеебо (Svante Pääbo) за «відкриття, що стосуються геномів вимерлих гомінідів і еволюції людини». Пояснюючи значення робіт С. Пеебо, Нобелівський комітет зазначив, що «він розробив методи аналізу та відновлення прадавньої ДНК. У давніх кістках ДНК розкладається, зазнає хімічного пошкодження, а також сильно забруднюється від контакту з бактеріями та людьми, які працюють зі зразками. Використовуючи наявні технології в міру їх розвитку, С. Пеебо створив власні методи для уточнення аналізу прадавньої ДНК».
For decades, interdisciplinary research efforts have accumulated insights that diminish the significance of the classic nature versus nurture dichotomy, instead calling for a nuanced, multifactorial approach to ontogeny. Similarly, the role of genes in both phylogeny and ontogeny, once seen as rather deterministic, is now conceptualized as highly dependent on environmental factors, including behavior. Linguistic theories have, in principle, made an effort to incorporate these changing views. However, the central claim of the given paper is that this apparent compliance with biological insights remains superficial. As such, considerable disconnects between linguistic theory and what is known about the biological underpinnings of complex traits persist, negatively impacting pertinent views on language acquisition, language universals and the evolution of language. Given the breadth of these fields of study, the aim of this paper is to tackle the root of the problem: It begins by sketching out linguistic nativism as conceptualized within generativism, pointing to aspects within this position that stand in conflict with the interdisciplinary literature. It will then review select areas of research in a succinct manner in order to substantiate the criticism and characterize the counterposition as found within the biological sciences. The paper will culminate in addressing these disconnects on conceptual grounds, i.e. invoking the term emergence as employed in neuroscience as a possible means to reconcile those biological insights with linguistic nativism.
The human louse, Pediculus humanus , is an obligate blood-sucking ectoparasite that has coevolved with humans for millennia. Given the intimate relationship between this parasite and the human host, the study of human lice has the potential to shed light on aspects of human evolution that are difficult to interpret using other biological evidence. In this study, we analyzed the genetic variation in 274 human lice from 25 geographic sites around the world by using nuclear microsatellite loci and female-inherited mitochondrial DNA sequences. Nuclear genetic diversity analysis revealed the presence of two distinct genetic clusters I and II, which are subdivided into subclusters: Ia-Ib and IIa-IIb, respectively. Among these samples, we observed the presence of the two most common louse mitochondrial haplogroups: A and B that were found in both nuclear Clusters I and II. Evidence of nuclear admixture was uncommon (12%) and was predominate in the New World potentially mirroring the history of colonization in the Americas. These findings were supported by novel DIYABC simulations that were built using both host and parasite data to define parameters and models suggesting that admixture between cI and cII was very recent. This pattern could also be the result of a reproductive barrier between these two nuclear genetic clusters. In addition to providing new evolutionary knowledge about this human parasite, our study could guide the development of new analyses in other host-parasite systems.
Denisovans, a group of now extinct humans who lived in Eastern Eurasia in the Middle and Late Pleistocene, were first identified from DNA sequences just over a decade ago. Only ten fragmentary remains from two sites have been attributed to Denisovans based entirely on molecular information. Nevertheless, there has been great interest in using genetic data to understand Denisovans and their place in human history. From the reconstruction of a single high-quality genome, it has been possible to infer their population history, including events of admixture with other human groups. Additionally, the identification of Denisovan DNA in the genomes of present-day individuals has provided insights into the timing and routes of dispersal of ancient modern humans into Asia and Oceania, as well as the contributions of archaic DNA to the physiology of present-day people. In this Review, we synthesize more than a decade of research on Denisovans, reconcile controversies and summarize insights into their population history and phenotype. We also highlight how our growing knowledge about Denisovans has provided insights into our own evolutionary history.
Neanderthals lived successfully in Europe and western Asia during the Middle Paleolithic period. Through the study of biological variables, it has been possible to shed light on the social life of Neanderthals. They led strenuous lives that involved hunting large game and gathering plant foods in order to meet the high energetic demands of life in their ever‐changing cold climate. Neanderthals lived in small bands of between ten and twenty adults along with their children. Genetic evidence has suggested that the females moved away whereas the males remained in their home band.
FOXP2 is a gene involved in language development and function. Neanderthals and humans share the same coding region of the gene, although the formers are thought to have exhibited less sophisticated language abilities. In this paper, we report on several human-specific changes in two functional enhancers of FOXP2. Two of these variants are located within the binding sites for the transcription factors POLR2A and SMARCC1, respectively. Interestingly, SMARCC1 is involved in brain development and vitamin D metabolism. We hypothesize that the human specific change in this position might have resulted in a different regulation pattern of FOXP2 expression in our species compared to extinct hominins, with a potential impact on our language abilities.
The Nobel Prize in Physiology or Medicine 2022 was awarded to Professor Svante Pääbo, a Swedish paleogenetic researcher, specialist in the field of evolutionary genetics, Director of the Department of Evolutionary Genetics at the Max Planck Institute for Evolutionary Anthropology of Leipzig (Germany), for “discoveries concerning the genomes of extinct hominids and human evolution”. Explaining the significance of S. Pääbo’s work, the Nobel Committee noted that “he pioneered the methods to isolate and analyze DNA from archaic bone remains. In ancient bones, DNA has decayed, been chemically damaged and massively contaminated with DNA from bacteria and contemporary humans who work with the samples. Having utilized modern genetic methods, S. Pääbo created his own methods of sequencing the ancient DNA”. Keywords: genome, hominids, human evolution, Nobel Prize in Physiology or Medicine 2022, Svante Pääbo
Since the publication of the first ancient DNA sequence in 1984, experimental methods used to recover ancient DNA have advanced greatly, illuminating previously unknown branches of the human family tree and opening up several promising new avenues for future studies of human evolution. The 2022 Nobel Prize in Physiology or Medicine was awarded to Svante Pääbo, director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, for his work on ancient DNA and human evolution. On his first day back at work, he was thrown in the pond as part of his institute's tradition of celebrating award winners.
In recent years, the increased availability of genomic data generated from ancient human remains has revolutionized the study of the past, and enabled researchers to tackle a range of questions that previously were targeted almost exclusively by disciplines in the Humanities such as History and Archaeology. Importantly, results obtained through characterizing the genetics of archaic hominins including evidence for adaptation, admixture, past demography, sex determination, or social structure, can be correlated with morphological and archaeological observations drawn from the fossil record. Admixture, defined as the exchange of genes between previously isolated species or populations, is now considered to be an important source of variation among ancient human lineages. The palaeogenomic studies are unravelling the complex evolutionary patterns of the human lineages, showing multiple admixture events in different moments and regions, as well as providing information on adaptations to environmental conditions, past migrations, demographic trends, and social structures.
Hominin origins are generally taken to refer to the patterns and processes involved in the divergence of hominins from their last common ancestor with the Pan clade. There are three sources of evidence on hominin origins. The first, broad only, is that given hominins are most closely related to the African apes, then their origins are likely to lie in Africa. The second is evolutionary genetics. The third line of evidence is the fossil record. The development of isotopic methods has had a major impact on human evolutionary studies. Stable isotopes can be used to trace aspects of life and the environment. While 3D morphometrics predates many of the developments in scanning technologies, these undoubtedly transformed the way in which palaeoanthropology is practized. There is no doubt that molecular genetics has transformed all of biology over the last half‐century, and this is especially true of hominin evolution.
It has recently become possible to start exploring how the genotype translates into human brain morphology and behavior by combining detailed genomic and phenotypic data from thousands of present-day people with archaic genomes of extinct humans, and gene expression data. As a starting point into this emerging interdisciplinary domain, we highlight current debates about which aspects of the modern human brain are unique. We review recent developments from (1) comparative primate neuroscience-a fast-growing field offering an invaluable framework for understanding general mechanisms and the evolution of human-specific traits. (2) paleoanthropology-based on evidence from endocranial imprints in fossil skulls, we trace the evolution from the ape-like brain phenotype of early hominins more than 3 million years ago to the unusual globular brain shape of present-day people. (3) Genomics of present-day and extinct humans. The morphological and genetic differences between modern humans and our closest extinct cousins, the Neandertals, offer important clues about the genetic underpinnings of brain morphology and behavior. The functional consequences of these genetic differences can be tested in animal models, and brain organoids.
Summary
The book contains the substance of the lectures and partly the practices of the subject of ‘Genetics and Genomics’ held in Semmelweis University for medical, pharmacological and dental students. The book updated in 2022 starts with a short introduction to basic genetics and molecular biology and then topics from human genetics mainly from medical point of views. Some of the 17 chapters deal with medical genetics, but the chapters also introduce to the basic knowledge of cell division, cytogenetics, epigenetics, developmental genetics, stem cell biology, oncogenetics, immunogenetics, population genetics, evolution genetics, nutrigenetics, and to a relative new subject, the human genomics and its applications for the study of the genomic background of complex diseases, pharmacogenomics and for the investigation of the genome environmental interactions. There is also a chapter about gene therapy. As genomics belongs to sytems biology, a chapter introduces to basic terms of systems biology, and concentrating on diseases. Some examples of the application and utilization of this scientific field are also be shown. The modern human genetics can also be associated with several ethical, social and legal issues. The last chapter of this book deals with these issues. At the end of each chapter there are questions, with which the readers can ascertain whether they understood and/or learned the chapter. Because it is an e-book, some terms and definitions have a hyperlink for more detailed explanations in the World Wide Web. Besides university students, the book is also recommended to all those who are interested in modern medical genetics and genomics and want to be up-to date in these subjects.
2022年诺贝尔生理学或医学奖的获奖者是著名生物学家、进化遗传学家斯万特•帕博(Svante Pääbo)。他通过研究已灭绝古人类的基因组，对探索人类演化作出了巨大贡献。文章介绍帕博及其团队关于尼安德特人和丹尼索瓦人的研究和发现，以及古DNA领域近30年的发展和最新成果。
In 1987, Phillip Tobias published a comprehensive anatomical analysis of the endocasts attributed to Homo habilis, discussing issues dealing with brain size, sulcal patterns, and vascular traces. He suggested that the neuroanatomy of this species evidenced a clear change toward many cerebral traits associated with our genus, mostly when concerning the morphology of the frontal and parietal cortex. After more than 30 years, the fossil record associated with this taxon has not grown that much, but we have much more information on cranial and brain biology, and we are using a larger array of digital methods to investigate the paleoneurological variation observed in the human genus. Brain volume, the size of the frontal lobe, or the gross hemispheric asymmetries are still relevant issues, but they are considered to be less central than before. More attention is instead being paid to the cortical organization, the relationships with the cranial architecture, and the influence of molecular or ecological factors. Although the field of paleoneurology can currently count on a larger range of tools and principles, there is still a general lack of anatomical information on many endocranial traits. This aspect is probably crucial for the agenda of paleoneurology. More importantly, the whole science is undergoing a delicate change, because of the growing influence of the social environment. In this sense, the disciplines working with fossils (and, in particular, with brain evolution) should take particular care to maintain a healthy professional situation, avoiding an excess of speculation and overstatement.
The reasons for the mysterious disappearance of Neanderthals about 40 thousand years ago, which occurred shortly after the appearance on their territory of people of the modern anatomical type - Cro-Magnons, occupy the minds of many generations of paleoanthropologists. The extinction of the Neanderthals lasted for 2-5 thousand years, depending on the habitat, which can be considered a fairly fast process, since before that they successfully lived in Western Europe for about 300 thousand years in the absence of any competition from other hominins. Several factors contributed to the extinction of the Neanderthals. The main one was demographic, which led to a sharp decline in the population, the cause of which was the superiority of the Cro-Magnons in intelligence and, possibly, their possession of articulate speech, which contributed to better organization in obtaining food. In addition, the Neanderthals' massive physique required more food, with Neanderthals and Cro-Magnons competing for the same resources and territories. It can be assumed that after the appearance of the Cro-Magnons, the Neanderthals lived from hand to mouth, which reduced their birth rate and increased mortality, and at a younger age compared to the Cro-Magnons. Climatic changes (Ice Age) affected, most likely, to a small extent, since the Neanderthals died out in the southern territories of their residence, where a sharp cooling did not occur. As one of the possible reasons for the extinction of the Neanderthals, one cannot exclude infections brought by the Cro-Magnons from Africa, to which the first were unstable. The article also discusses the social aspect: the predecessors of the Neanderthals were probably the first wave of people from Africa who came to the territory of present-day Western Europe about 600 thousand years ago; the second wave can be considered the Cro-Magnons, who followed the same path from Africa through the Near and Middle East. In the coming third millennium of the new era, Western Europe is already facing the third wave of migrants - Afrasians, following almost the same path. It can be assumed that due to the better birth rate among the latter and a number of other circumstances, in a few generations the autochthonous population of Europe will be replaced by newcomers, including through assimilation.
The interface of sexual behavior and evolutionary psychology is a rapidly growing domain, rich in psychological theories and data as well as controversies and applications. With nearly eighty chapters by leading researchers from around the world, and combining theoretical and empirical perspectives, The Cambridge Handbook of Evolutionary Perspectives on Sexual Psychology is the most comprehensive and up-to-date reference work in the field. Providing a broad yet in-depth overview of the various evolutionary principles that influence all types of sexual behaviors, the handbook takes an inclusive approach that draws on a number of disciplines and covers nonhuman and human psychology. It is an essential resource for both established researchers and students in psychology, biology, anthropology, medicine, and criminology, among other fields. Volume 4: Controversies, Applications, and Nonhuman Primate Extensions addresses controversies and unresolved issues; applications to health, law, and pornography; and non-human primate evolved sexual psychology.
Development of the brain and the emergence of the mind constitute some of the most important concerns of contemporary biology. Disturbances during fetal life may have profound implications for a child's future neurological and psychological development, which can in turn impact society. The new edition of this highly respected work presents a comprehensive review of the basic mechanisms of brain development and the pathophysiology of disorders of the infant brain, written by a team of distinguished neuroscientists, neonatologists, and neuropediatricians. The book follows the main milestones of brain development, from formation of the neural tube and wiring of the neurons in the brain. Neurotrophic factors, neurotransmitters, glial cell biology, cerebral circulation development of sensory functions are all described in detail. Furthermore, there are more philosophical chapters on the evolution of the brain and the emergence of consciousness. Clinical considerations are highlighted where relevant.
Development of the brain and the emergence of the mind constitute some of the most important concerns of contemporary biology. Disturbances during fetal life may have profound implications for a child's future neurological and psychological development, which can in turn impact society. The new edition of this highly respected work presents a comprehensive review of the basic mechanisms of brain development and the pathophysiology of disorders of the infant brain, written by a team of distinguished neuroscientists, neonatologists, and neuropediatricians. The book follows the main milestones of brain development, from formation of the neural tube and wiring of the neurons in the brain. Neurotrophic factors, neurotransmitters, glial cell biology, cerebral circulation development of sensory functions are all described in detail. Furthermore, there are more philosophical chapters on the evolution of the brain and the emergence of consciousness. Clinical considerations are highlighted where relevant.
Development of the brain and the emergence of the mind constitute some of the most important concerns of contemporary biology. Disturbances during fetal life may have profound implications for a child's future neurological and psychological development, which can in turn impact society. The new edition of this highly respected work presents a comprehensive review of the basic mechanisms of brain development and the pathophysiology of disorders of the infant brain, written by a team of distinguished neuroscientists, neonatologists, and neuropediatricians. The book follows the main milestones of brain development, from formation of the neural tube and wiring of the neurons in the brain. Neurotrophic factors, neurotransmitters, glial cell biology, cerebral circulation development of sensory functions are all described in detail. Furthermore, there are more philosophical chapters on the evolution of the brain and the emergence of consciousness. Clinical considerations are highlighted where relevant.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
The discovery of the first species of African hominin, Australopithecus africanus, from Taung, South Africa in 1924, launched the study of fossil man in Africa. New discoveries continue to confirm the importance of this region to our understanding of human evolution. Outlining major developments since Raymond Dart's description of the Taung skull and, in particular, the impact of the pioneering work of Phillip V. Tobias, this book will be a valuable companion for students and researchers of human origins. It presents a summary of the current state of palaeoanthropology, reviewing the ideas that are central to the field, and provides a perspective on how future developments will shape our knowledge about hominin emergence in Africa. A wide range of key themes are covered, from the earliest fossils from Chad and Kenya, to the origins of bipedalism and the debate about how and where modern humans evolved and dispersed across Africa.
Individuals affected with developmental disorders of speech and language have substantial difficulty acquiring expressive and/or receptive language in the absence of any profound sensory or neurological impairment and despite adequate intelligence and opportunity(1). Although studies of twins consistently indicate that a significant genetic component is involved(1-3), most families segregating speech and language deficits show complex patterns of inheritance, and a gene that predisposes individuals to such disorders has not been identified. We have studied a unique three-generation pedigree, KE, in which a severe speech and language disorder is transmitted as an autosomal-dominant monogenic trait(4). Our previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region 7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in whom speech and language impairment is associated with a chromosomal translocation involving the SPCH1 interval(6). Here we show that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is directly disrupted by the translocation breakpoint in CS. In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain. Our findings suggest that FOXP2 is involved in the developmental process that culminates in speech and language.
DNA that has been recovered from archaeological and palaeontological remains
makes it possible to go back in time and study the genetic relationships of
extinct organisms to their contemporary relatives. This provides a new perspective
on the evolution of organisms and DNA sequences. However, the field is fraught
with technical pitfalls and needs stringent criteria to ensure the reliability
of results, particularly when human remains are studied.
Ancient DNA analyses rely on the extraction of the tiny amounts of DNA remaining in samples that are hundreds to tens of thousands of years old. Despite the critical role extraction efficiency plays in this field of research, no study has comprehensively compared ancient DNA extraction techniques to date. There are a wide range of methods currently in use, which rely on such disparate principles as spin columns, alcohol precipitation, or binding to silica. We have compared a number of these methods using quantitative PCR and then optimized each step of the most promising method. We found that most chemicals routinely added to ancient DNA extraction buffers do not increase, and sometimes even decrease, DNA yields. Consequently, our optimized method uses a buffer consisting solely of EDTA and proteinase K for bone digestion and binding DNA to silica via guanidinium thiocyanate for DNA purification. In a comparison with published methods, this minimalist approach, on average, outperforms all other methods in terms of DNA yields as measured using quantitative PCR. We also found that the addition of bovine serum albumin (BSA) to the PCR helps to overcome inhibitors in ancient DNA extracts. Finally, we observed a marked difference in the performance between different types of DNA polymerases, as measured by amplification success.
Noninvasive samples are useful for molecular genetic analyses of wild animal populations. However, the low DNA content of such samples makes DNA amplification difficult, and there is the potential for erroneous results when one of two alleles at heterozygous microsatellite loci fails to be amplified. In this study we describe an assay designed to measure the amount of amplifiable nuclear DNA in low DNA concentration extracts from noninvasive samples. We describe the range of DNA amounts obtained from chimpanzee faeces and shed hair samples and formulate a new efficient approach for accurate micro-satellite genotyping. Prescreening of extracts for DNA quantity is recommended for sorting of samples for likely success and reliability. Repetition of results remains extensive for analysis of microsatellite amplifications beginning from low starting amounts of DNA, but is reduced for those with higher DNA content.
We consider a data set of DNA sequence variation at three Y chromosome genes (SMCY, DBY, and DFFRY) in a worldwide sample of human Y chromosomes. Between 53 and 70 chromosomes were fully screened for sequence variation at each locus by using the method of denaturing high-performance liquid chromatography. The sum of the lengths of the three genes is 64,120 bp. We have used these data to study the ancestral genealogy of human Y chromosomes. In particular, we focused on estimating the expected time to the most recent common ancestor and the expected ages of certain mutations with interesting geographic distributions. Although the geographic structure of the inferred haplotype tree is reminiscent of that obtained for other loci (the root is in Africa, and most of the oldest non-African lineages are Asian), the expected time to the most recent common ancestor is remarkably short, on the order of 50,000 years. Thus, although previous studies have noted that Y chromosome variation shows extreme geographic structure, we estimate that the spread of Y chromosomes out of Africa is much more recent than previously was thought. We also show that our data indicate substantial population growth in the effective number of human Y chromosomes.
Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago.
We show that DNA molecules amplified by PCR from DNA extracted from animal bones and teeth that vary in age between 25 000
and over 50 000 years carry C→T and G→A substitutions. These substitutions can reach high proportions among the molecules
amplified and are due to the occurrence of modified deoxycytidine residues in the template DNA. If the template DNA is treated
with uracil N-glycosylase, these substitutions are dramatically reduced. They are thus likely to result from deamination of deoxycytidine
residues. In addition, ‘jumping PCR’, i.e. the occurrence of template switching during PCR, may contribute to these substitutions.
When DNA sequences are amplified from ancient DNA extracts where few template molecules initiate the PCR, precautions such
as DNA sequence determination of multiple clones derived from more than one independent amplification are necessary in order
to reduce the risk of determination of incorrect DNA sequences. When such precautionary measures are taken, errors induced
by damage to the DNA template are unlikely to be more frequent than ∼0.1% even under the unlikely scenario where each amplification
starts from a single template molecule.
Language is a uniquely human trait likely to have been a prerequisite for the development of human culture. The ability to develop articulate speech relies on capabilities, such as fine control of the larynx and mouth, that are absent in chimpanzees and other great apes. FOXP2 is the first gene relevant to the human ability to develop language. A point mutation in FOXP2 co-segregates with a disorder in a family in which half of the members have severe articulation difficulties accompanied by linguistic and grammatical impairment. This gene is disrupted by translocation in an unrelated individual who has a similar disorder. Thus, two functional copies of FOXP2 seem to be required for acquisition of normal spoken language. We sequenced the complementary DNAs that encode the FOXP2 protein in the chimpanzee, gorilla, orang-utan, rhesus macaque and mouse, and compared them with the human cDNA. We also investigated intraspecific variation of the human FOXP2 gene. Here we show that human FOXP2 contains changes in amino-acid coding and a pattern of nucleotide polymorphism, which strongly suggest that this gene has been the target of selection during recent human evolution.
That speech and language are innate capacities of the human brain has long been widely accepted, but only recently has an entry point into the genetic basis of these remarkable faculties been found. The discovery of a mutation in FOXP2 in a family with a speech and language disorder has enabled neuroscientists to trace the neural expression of this gene during embryological development, track the effects of this gene mutation on brain structure and function, and so begin to decipher that part of our neural inheritance that culminates in articulate speech.
In studying the genomes of extinct species, two principal limitations are typically the small quantities of endogenous ancient DNA and its degraded condition, even though products of up to 1,600 base pairs (bp) have been amplified in rare cases. Using small overlapping polymerase chain reaction products, longer stretches of sequences or even whole mitochondrial genomes can be reconstructed, but this approach is limited by the number of amplifications that can be performed from rare samples. Thus, even from well-studied Pleistocene species such as mammoths, ground sloths and cave bears, no DNA sequences of more than about 1,000 bp have been reconstructed. Here we report the complete mitochondrial genome sequence of the Pleistocene woolly mammoth Mammuthus primigenius. We used about 200 mg of bone and a new approach that allows the simultaneous retrieval of multiple sequences from small amounts of degraded DNA. Our phylogenetic analyses show that the mammoth was more closely related to the Asian than to the African elephant. However, the divergence of mammoth, African and Asian elephants occurred over a short time, corresponding to only about 7% of the total length of the phylogenetic tree for the three evolutionary lineages.
Although ancient DNA (aDNA) miscoding lesions have been studied since the earliest days of the field, their nature remains a source of debate. A variety of conflicting hypotheses exist about which miscoding lesions constitute true aDNA damage as opposed to PCR polymerase amplification error. Furthermore, considerable disagreement and speculation exists on which specific damage events underlie observed miscoding lesions. The root of the problem is that it has previously been difficult to assemble sufficient data to test the hypotheses, and near-impossible to accurately determine the specific strand of origin of observed damage events. With the advent of emulsion-based clonal amplification (emPCR) and the sequencing-by-synthesis technology this has changed. In this paper we demonstrate how data produced on the Roche GS20 genome sequencer can determine miscoding lesion strands of origin, and subsequently be interpreted to enable characterization of the aDNA damage behind the observed phenotypes. Through comparative analyses on 390,965 bp of modern chloroplast and 131,474 bp of ancient woolly mammoth GS20 sequence data we conclusively demonstrate that in this sample at least, a permafrost preserved specimen, Type 2 (cytosine-->thymine/guanine-->adenine) miscoding lesions represent the overwhelming majority of damage-derived miscoding lesions. Additionally, we show that an as yet unidentified guanine-->adenine analogue modification, not the conventionally argued cytosine-->uracil deamination, underpins a significant proportion of Type 2 damage. How widespread these implications are for aDNA will become apparent as future studies analyse data recovered from a wider range of substrates.
Whereas evolutionary inferences derived from present-day DNA sequences are by necessity indirect, ancient DNA sequences provide a direct view of past genetic variants. However, base lesions that accumulate in DNA over time may cause nucleotide misincorporations when ancient DNA sequences are replicated. By repeated amplifications of mitochondrial DNA sequences from a large number of ancient wolf remains, we show that C/G-to-T/A transitions are the predominant type of such misincorporations. Using a massively parallel sequencing method that allows large numbers of single DNA strands to be sequenced, we show that modifications of C, as well as to a lesser extent of G, residues cause such misincorporations. Experiments where oligonucleotides containing modified bases are used as templates in amplification reactions suggest that both of these types of misincorporations can be caused by deamination of the template bases. New DNA sequencing methods in conjunction with knowledge of misincorporation processes have now, in principle, opened the way for the determination of complete genomes from organisms that became extinct during and after the last glaciation.
• pyrosequencing
• deamination
• DNA damage
• wolves
• mammoth
Neanderthals are the extinct hominid group most closely related to contemporary humans, so their genome offers a unique opportunity to identify genetic changes specific to anatomically fully modern humans. We have identified a 38,000-year-old Neanderthal fossil that is exceptionally free of contamination from modern human DNA. Direct high-throughput sequencing of a DNA extract from this fossil has thus far yielded over one million base pairs of hominoid nuclear DNA sequences. Comparison with the human and chimpanzee genomes reveals that modern human and Neanderthal DNA sequences diverged on average about 500,000 years ago. Existing technology and fossil resources are now sufficient to initiate a Neanderthal genome-sequencing effort.
Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where the human genomic sequence is different. These results enabled us to calculate the human-Neanderthal divergence time based on multiple randomly distributed autosomal loci. Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent common ancestor approximately 706,000 years ago, and that the human and Neanderthal ancestral populations split approximately 370,000 years ago, before the emergence of anatomically modern humans. Our finding that the Neanderthal and human genomes are at least 99.5% identical led us to develop and successfully implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics.
Fossil evidence from the Iberian Peninsula is essential for understanding Neandertal evolution and history. Since 2000, a new sample approximately 43,000 years old has been systematically recovered at the El Sidrón cave site (Asturias, Spain). Human remains almost exclusively compose the bone assemblage. All of the skeletal parts are preserved, and there is a moderate occurrence of Middle Paleolithic stone tools. A minimum number of eight individuals are represented, and ancient mtDNA has been extracted from dental and osteological remains. Paleobiology of the El Sidrón archaic humans fits the pattern found in other Neandertal samples: a high incidence of dental hypoplasia and interproximal grooves, yet no traumatic lesions are present. Moreover, unambiguous evidence of human-induced modifications has been found on the human remains. Morphologically, the El Sidrón humans show a large number of Neandertal lineage-derived features even though certain traits place the sample at the limits of Neandertal variation. Integrating the El Sidrón human mandibles into the larger Neandertal sample reveals a north-south geographic patterning, with southern Neandertals showing broader faces with increased lower facial heights. The large El Sidrón sample therefore augments the European evolutionary lineage fossil record and supports ecogeographical variability across Neandertal populations.
Heterogeneity in the genome copy number of tissues is of particular importance in solid tumor biology. Furthermore, many clinical
applications such as pre-implantation and non-invasive prenatal diagnosis would benefit from the ability to characterize individual
single cells. As the amount of DNA from single cells is so small, several PCR protocols have been developed in an attempt
to achieve unbiased amplification. Many of these approaches are suitable for subsequent cytogenetic analyses using conventional
methodologies such as comparative genomic hybridization (CGH) to metaphase spreads. However, attempts to harness array-CGH
for single-cell analysis to provide improved resolution have been disappointing. Here we describe a strategy that combines
single-cell amplification using GenomePlex library technology (GenomePlex® Single Cell Whole Genome Amplification Kit, Sigma-Aldrich, UK) and detailed analysis of genomic copy number changes by high-resolution
array-CGH. We show that single copy changes as small as 8.3 Mb in single cells are detected reliably with single cells derived
from various tumor cell lines as well as patients presenting with trisomy 21 and Prader–Willi syndrome. Our results demonstrate
the potential of this technology for studies of tumor biology and for clinical diagnostics.
Ancient DNA (aDNA) research has long depended on the power of PCR to amplify trace amounts of surviving genetic material from preserved specimens. While PCR permits specific loci to be targeted and amplified, in many ways it can be intrinsically unsuited to damaged and degraded aDNA templates. PCR amplification of aDNA can produce highly-skewed distributions with significant contributions from miscoding lesion damage and non-authentic sequence artefacts. As traditional PCR-based approaches have been unable to fully resolve the molecular nature of aDNA damage over many years, we have developed a novel single primer extension (SPEX)-based approach to generate more accurate sequence information. SPEX targets selected template strands at defined loci and can generate a quantifiable redundancy of coverage; providing new insights into the molecular nature of aDNA damage and fragmentation. SPEX sequence data reveals inherent limitations in both traditional and metagenomic PCR-based approaches to aDNA, which can make current damage analyses and correct genotyping of ancient specimens problematic. In contrast to previous aDNA studies, SPEX provides strong quantitative evidence that C > U-type base modifications are the sole cause of authentic endogenous damage-derived miscoding lesions. This new approach could allow ancient specimens to be genotyped with unprecedented accuracy.
High-throughput direct sequencing techniques have recently opened the possibility to sequence genomes from Pleistocene organisms. Here we analyze DNA sequences determined from a Neandertal, a mammoth, and a cave bear. We show that purines are overrepresented at positions adjacent to the breaks in the ancient DNA, suggesting that depurination has contributed to its degradation. We furthermore show that substitutions resulting from miscoding cytosine residues are vastly overrepresented in the DNA sequences and drastically clustered in the ends of the molecules, whereas other substitutions are rare. We present a model where the observed substitution patterns are used to estimate the rate of deamination of cytosine residues in single- and double-stranded portions of the DNA, the length of single-stranded ends, and the frequency of nicks. The results suggest that reliable genome sequences can be obtained from Pleistocene organisms.
• 454
• deamination
• depurination
• paleogenomics
The genetic divergence time between two species varies substantially across the genome, conveying important information about the timing and process of speciation. Here we develop a framework for studying this variation and apply it to about 20 million base pairs of aligned sequence from humans, chimpanzees, gorillas and more distantly related primates. Human–chimpanzee genetic divergence varies from less than 84% to more than 147% of the average, a range of more than 4 million years. Our analysis also shows that human–chimpanzee speciation occurred less than 6.3 million years ago and probably more recently, conflicting with some interpretations of ancient fossils. Most strikingly, chromosome X shows an extremely young genetic divergence time, close to the genome minimum along nearly its entire length. These unexpected features would be explained if the human and chimpanzee lineages initially diverged, then later exchanged genes before separating permanently.
Abstract Considerable interest is focused on the use of polymorphism data to identify regions of the genome that underlie recent adaptations. These searches are guided by a simple model of positive selection, in which a mutation is favored as soon as it arises. This assumption may not be realistic, as environmental changes and range expansions may lead previously neutral or deleterious alleles to become beneficial. We examine what effect this mode of selection has on patterns of variation at linked neutral sites by implementing a new coalescent model of positive directional selection on standing variation. In this model, a neutral allele arises and drifts in the population, then at frequency f becomes beneficial, and eventually reaches fixation. Depending on the value of f, this scenario can lead to a large variance in allele frequency spectra and in levels of linkage disequilibrium at linked, neutral sites. In particular, for intermediate f, the beneficial substitution often leads to a loss of rare alleles–a pattern that differs markedly from the signature of directional selection currently relied on by researchers. These findings highlight the importance of an accurate characterization of the effects of positive selection, if we are to reliably identify recent adaptations from polymorphism data.
The origin, history, and singularity of our species has fascinated storytellers, philosophers and scientists throughout, and doubtless before, recorded history. Anthropology, the modern-era discipline that deals with these issues, is a notoriously contentious field, perhaps because the topic at hand - the nature of our own species - is one that is difficult or impossible to approach in an unbiased way. Recently, molecular genetics has increasingly contributed to this field. Here, I briefly discuss three areas where I believe molecular studies are likely to be of decisive importance in the future. These concern the questions of where and when our species originated, what the genetic background for characters that differ between us and apes is, and how the phenotypic traits that vary among human groups have evolved.
Noninvasive samples are useful for molecular genetic analyses of wild animal populations. However, the low DNA content of such samples makes DNA amplification difficult, and there is the potential for erroneous results when one of two alleles at heterozygous microsatellite loci fails to be amplified. In this study we describe an assay designed to measure the amount of amplifiable nuclear DNA in low DNA concentration extracts from noninvasive samples. We describe the range of DNA amounts obtained from chimpanzee faeces and shed hair samples and formulate a new efficient approach for accurate microsatellite genotyping. Prescreening of extracts for DNA quantity is recommended for sorting of samples for likely success and reliability. Repetition of results remains extensive for analysis of microsatellite amplifications beginning from low starting amounts of DNA, but is reduced for those with higher DNA content.
Genes responsible for human-specific phenotypes may have been under altered selective pressures in human evolution and thus exhibit changes in substitution rate and pattern at the protein sequence level. Using comparative analysis of human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and FOXP2) with significantly enhanced evolutionary rates in the hominid lineage. PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely target of sexual selection in humans and chimpanzees. FOXP2 is a transcription factor involved in speech and language development. Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated two fixed amino acid changes in a broadly defined transcription suppression domain. A survey of a diverse group of placental mammals reveals the uniqueness of the human FOXP2 sequence and a population genetic analysis indicates possible adaptive selection behind the accelerated evolution. Taken together, our results suggest an important role that FOXP2 may have played in the origin of human speech and demonstrate a strategy for identifying candidate genes underlying the emergences of human-specific features.
FOXP2, the first gene to have been implicated in a developmental communication disorder, offers a unique entry point into neuromolecular mechanisms influencing human speech and language acquisition. In multiple members of the well-studied KE family, a heterozygous missense mutation in FOXP2 causes problems in sequencing muscle movements required for articulating speech (developmental verbal dyspraxia), accompanied by wider deficits in linguistic and grammatical processing. Chromosomal rearrangements involving this locus have also been identified. Analyses of FOXP2 coding sequence in typical forms of specific language impairment (SLI), autism, and dyslexia have not uncovered any etiological variants. However, no previous study has performed mutation screening of children with a primary diagnosis of verbal dyspraxia, the most overt feature of the disorder in affected members of the KE family. Here, we report investigations of the entire coding region of FOXP2, including alternatively spliced exons, in 49 probands affected with verbal dyspraxia. We detected variants that alter FOXP2 protein sequence in three probands. One such variant is a heterozygous nonsense mutation that yields a dramatically truncated protein product and cosegregates with speech and language difficulties in the proband, his affected sibling, and their mother. Our discovery of the first nonsense mutation in FOXP2 now opens the door for detailed investigations of neurodevelopment in people carrying different etiological variants of the gene. This endeavor will be crucial for gaining insight into the role of FOXP2 in human cognition.
Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.
Molecular clocks have been used to date the divergence of humans and chimpanzees for nearly four decades. Nonetheless, this date and its confidence interval remain to be firmly established. In an effort to generate a genomic view of the human–chimpanzee divergence, we have analyzed 167 nuclear protein-coding genes and built a reliable confidence interval around the calculated time by applying a multifactor bootstrap-resampling approach. Bayesian and maximum likelihood analyses of neutral DNA substitutions show that the human–chimpanzee divergence is close to 20% of the ape–Old World monkey (OWM) divergence. Therefore, the generally accepted range of 23.8–35 millions of years ago for the ape–OWM divergence yields a range of 4.98–7.02 millions of years ago for human–chimpanzee divergence. Thus, the older time estimates for the human–chimpanzee divergence, from molecular and paleontological studies, are unlikely to be correct. For a given the ape–OWM divergence time, the 95% confidence interval of the human–chimpanzee divergence ranges from –12% to 19% of the estimated time. Computer simulations suggest that the 95% confidence intervals obtained by using a multifactor bootstrap-resampling approach contain the true value with >95% probability, whether deviations from the molecular clock are random or correlated among lineages. Analyses revealed that the use of amino acid sequence differences is not optimal for dating human–chimpanzee divergence and that the inclusion of additional genes is unlikely to narrow the confidence interval significantly. We conclude that tests of hypotheses about the timing of human–chimpanzee divergence demand more precise fossil-based calibrations.
• Bayesian analysis
• molecular clock
• hominid
• fossil
• primate
Considerable interest is focused on the use of polymorphism data to identify regions of the genome that underlie recent adaptations. These searches are guided by a simple model of positive selection, in which a mutation is favored as soon as it arises. This assumption may not be realistic, as environmental changes and range expansions may lead previously neutral or deleterious alleles to become beneficial. We examine what effect this mode of selection has on patterns of variation at linked neutral sites by implementing a new coalescent model of positive directional selection on standing variation. In this model, a neutral allele arises and drifts in the population, then at frequency f becomes beneficial, and eventually reaches fixation. Depending on the value of f, this scenario can lead to a large variance in allele frequency spectra and in levels of linkage disequilibrium at linked, neutral sites. In particular, for intermediate f, the beneficial substitution often leads to a loss of rare alleles--a pattern that differs markedly from the signature of directional selection currently relied on by researchers. These findings highlight the importance of an accurate characterization of the effects of positive selection, if we are to reliably identify recent adaptations from polymorphism data.
Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits Current Biology Vol 17 No 21 4 CURBIO 5970 Please cite this article in press as: Krause et al., The Derived FOXP2 Variant of Modern Humans Was Shared with Neandertals doi:10.1016/j.cub
- K D Macdermot
- E Bonora
- N Sykes
- A M Coupe
- C S Lai
- S C Vernes
- Vargha
- F Khadem
- F Mckenzie
- R L Smith
- A P Monaco
- S E Fisher
MacDermot, K.D., Bonora, E., Sykes, N., Coupe, A.M., Lai, C.S., Vernes, S.C., Vargha-Khadem, F., McKenzie, F., Smith, R.L., Monaco, A.P., and Fisher, S.E. (2005). Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits. Am. J. Hum. Genet. 76, 1074–1080. Current Biology Vol 17 No 21 4 CURBIO 5970 Please cite this article in press as: Krause et al., The Derived FOXP2 Variant of Modern Humans Was Shared with Neandertals, Current Biology (2007), doi:10.1016/j.cub.2007.10.008 3. Vargha-Khadem, F., Gadian, D.G., Copp, A., and Mishkin, M. (2005). FOXP2 and the neuroanatomy of speech and language. Nat. Rev. Neurosci. 6, 131–138.
helped design the control experiment; W.E. assisted in the interpretation of the results; C.H. coordinated the work in Lyon
- .-F Extracted
J.K., L.O., and C.L.-F. extracted, amplified, sequenced, and analyzed ancient DNA; E.G. and H.B. helped design the control experiment; W.E. assisted in the interpretation of the results; C.H. coordinated the work in Lyon; J.B. provided laboratory space in Bar-celona;
Recent common ancestry of human Y chromosomes: evidence from DNA sequence data.
- Thomson R.
- Pritchard J.K.
- Shen P.
- Oefner P.J.
- Feldman M.W.
A forkhead-domain gene is mutated in a severe speech and language disorder
- Lai
Recent common ancestry of human Y chromosomes: evidence from DNA sequence data
- Thomson