Complex History of Admixture between Modern Humans and Neandertals

Recent analyses have found that a substantial amount of the Neandertal genome persists in the genomes of contemporary non-African individuals. East Asians have, on average, higher levels of Neandertal ancestry than do Europeans, which might be due to differences in the efficiency of purifying selection, an additional pulse of introgression into East Asians, or other unexplored scenarios. To better define the scope of plausible models of archaic admixture between Neandertals and anatomically modern humans, we analyzed patterns of introgressed sequence in whole-genome data of 379 Europeans and 286 East Asians. We found that inferences of demographic history restricted to neutrally evolving genomic regions allowed a simple one-pulse model to be robustly rejected, suggesting that differences in selection cannot explain the differences in Neandertal ancestry. We show that two additional demographic models, involving either a second pulse of Neandertal gene flow into the ancestors of East Asians or a dilution of Neandertal lineages in Europeans by admixture with an unknown ancestral population, are consistent with the data. Thus, the history of admixture between modern humans and Neandertals is most likely more complex than previously thought.     

The Neandertal genome and ancient DNA authenticity

Recent advances in high‐thoughput DNA sequencing have made genome‐scale analyses of genomes of extinct organisms possible. With these new opportunities come new difficulties in assessing the authenticity of the DNA sequences retrieved. We discuss how these difficulties can be addressed, particularly with regard to analyses of the Neandertal genome. We argue that only direct assays of DNA sequence positions in which Neandertals differ from all contemporary humans can serve as a reliable means to estimate human contamination. Indirect measures, such as the extent of DNA fragmentation, nucleotide misincorporations, or comparison of derived allele frequencies in different fragment size classes, are unreliable. Fortunately, interim approaches based on mtDNA differences between Neandertals and current humans, detection of male contamination through Y chromosomal sequences, and repeated sequencing from the same fossil to detect autosomal contamination allow initial large‐scale sequencing of Neandertal genomes. This will result in the discovery of fixed differences in the nuclear genome between Neandertals and current humans that can serve as future direct assays for contamination. For analyses of other fossil hominins, which may become possible in the future, we suggest a similar ‘boot‐strap’ approach in which interim approaches are applied until sufficient data for more definitive direct assays are acquired.     

Differences between Neandertal and modern human infant and child growth models

Studying the emergence of distinctive human growth patterns is essential to understanding the evolution of our species. The large number of Neandertal fossils makes this species the best candidate for a comparative study of growth patterns in archaic and modern humans. Here, Neandertal height growth during infancy and early childhood is described using a mathematical model. Height growth velocities for individuals five years old or younger are modelled as age functions based on different estimates of height and age for a set of ten Neandertal infants and children. The estimated heights of each Neandertal individual are compared with those of two modern human populations based on longitudinal and cross-sectional data. The model highlights differences in growth velocity during infancy (from the age of five months onward). We find that statural growth in Neandertal infants is much slower than that seen in modern humans, Neandertal growth is similar to modern humans at birth, but decreases around the third or fourth month. The markedly slower growth rates of Neandertal infants may be attributable to ontogenetic constraints or to metabolic stress, and contribute to short achieved adult stature relative to modern humans.     

A genetic legacy from archaic Homo

The roles of fossil human populations in the origin of modern humans have been enigmatic. Earlier (archaic) human populations were biologically similar and were in recurrent temporal and geographic contact, making interbreeding between ancient populations likely. Regardless of the taxonomic status of these populations, adaptive alleles may have introgressed from archaic populations into modern humans. When an introgressed archaic allele has a selective advantage, even rare interbreeding can lead to its spread or fixation in later human populations. Several genetic loci are candidates for such introgression, including microcephalin, a gene influencing brain development. This example may suggest that the evolution of human cognition depended in part on the genetic legacy of archaic groups such as the Neanderthals.     

The gut microbiota links disease to human genome evolution

A large number of studies have established a causal relationship between the gut microbiota and human disease. In addition, the composition of the microbiota is substantially influenced by the human genome. Modern medical research has confirmed that the pathogenesis of various diseases is closely related to evolutionary events in the human genome. Specific regions of the human genome known as human accelerated regions (HARs) have evolved rapidly over several million years since humans diverged from a common ancestor with chimpanzees, and HARs have been found to be involved in some human-specific diseases. Furthermore, the HAR-regulated gut microbiota has undergone rapid changes during human evolution. We propose that the gut microbiota may serve as an important mediator linking diseases to human genome evolution.     

Neanderthal genomics suggests a pleistocene time frame for the first epidemiologic transition

High quality Altai Neanderthal and Denisovan genomes are revealing which regions of archaic hominin DNA have persisted in the modern human genome. A number of these regions are associated with response to infection and immunity, with a suggestion that derived Neanderthal alleles found in modern Europeans and East Asians may be associated with autoimmunity. As such Neanderthal genomes are an independent line of evidence of which infectious diseases Neanderthals were genetically adapted to. Sympathetically, human genome adaptive introgression is an independent line of evidence of which infectious diseases were important for AMH coming in to Eurasia and interacting with Neanderthals. The Neanderthals and Denisovans present interesting cases of hominin hunter‐gatherers adapted to a Eurasian rather than African infectious disease package. Independent sources of DNA‐based evidence allow a re‐evaluation of the first epidemiologic transition and how infectious disease affected Pleistocene hominins. By combining skeletal, archaeological and genetic evidence from modern humans and extinct Eurasian hominins, we question whether the first epidemiologic transition in Eurasia featured a new package of infectious diseases or a change in the impact of existing pathogens. Coupled with pathogen genomics, this approach supports the view that many infectious diseases are pre‐Neolithic, and the list continues to expand. The transfer of pathogens between hominin populations, including the expansion of pathogens from Africa, may also have played a role in the extinction of the Neanderthals and offers an important mechanism to understand hominin–hominin interactions well back beyond the current limits for aDNA extraction from fossils alone. Am J Phys Anthropol 160:379–388, 2016. © 2016 Wiley Periodicals, Inc.     

Genomic data reveal a complex making of humans

In the last few years, two paradigms underlying human evolution have crumbled. Modern humans have not totally replaced previous hominins without any admixture, and the expected signatures of adaptations to new environments are surprisingly lacking at the genomic level. Here we review current evidence about archaic admixture and lack of strong selective sweeps in humans. We underline the need to properly model differential admixture in various populations to correctly reconstruct past demography. We also stress the importance of taking into account the spatial dimension of human evolution, which proceeded by a series of range expansions that could have promoted both the introgression of archaic genes and background selection.     

Brain Size Growth and Life History in Human Evolution

Increases in endocranial volume (a measure of brain size) play a major role in human evolution. Despite the importance of brain size increase, the developmental bases of human brain size evolution remain poorly characterized. Comparative analyses of endocranial volume size growth illustrate that distinctions between humans and other primates are consequences of differences in rates of brain size growth, with little evidence for differences in growth duration. Evaluation of available juvenile fossils shows that earliest hominins do not differ perceptibly from chimpanzees (Pan). However, rapid and human-like early brain growth apparently characterized Homo erectus at about 1?Ma before present. Neandertals show patterns of brain growth consistent with modern humans during infancy, but reach larger sizes than modern humans as a result of differences in later growth. Growth analyses reveal commonalities in patterns of early brain size growth during the last million years human evolution, despite major increases in adult size. This result implies consistency across hominins in terms of maternal metabolic costs of infancy. Continued size growth past infancy in Neandertals and modern humans, when compared to earlier hominins, may have cognitive implications. Differences between Neandertals and modern humans are implied, but difficult to define with certainty.     

A functional test of Neandertal and modern human mitochondrial targeting sequences

Targeting of nuclear-encoded proteins to different organelles, such as mitochondria, is a process that can result in the redeployment of proteins to new intracellular destinations during evolution. With the sequencing of the Neandertal genome, it has become possible to identify amino acid substitutions that occurred on the modern human lineage since its separation from the Neandertal lineage. Here we analyze the function of two substitutions in mitochondrial targeting sequences that occurred and rose to high frequency recently during recent human evolution. The ancestral and modern versions of the two targeting sequences do not differ in the efficiency with which they direct a protein to the mitochondria, an observation compatible with the neutral theory of molecular evolution.     

Archaic and modern human distal humeral morphology

The morphology of the proximal ulna has been shown to effectively differentiate archaic or premodern humans (such as Homo heidelbergensis and H. neanderthalensis) from modern humans (H. sapiens). Accordingly, the morphology of adjacent, articulating elements should be able to distinguish these two broad groups as well. Here we test the taxonomic utility of another portion of the elbow, the distal humerus, as a discriminator of archaic and modern humans. Principal components analysis was employed on a suite of log-raw and log-shape distal humeral measures to examine differences between Neandertal and modern human distal humeri. In addition, the morphological affinities of Broken Hill (Kabwe) E.898, an archaic human distal humeral fragment from the middle Pleistocene of Zambia, and five Pliocene and early Pleistocene australopith humeri were assessed. The morphometric analyses effectively differentiated the Neandertals from the other groups, while the Broken Hill humerus appears morphologically similar to modern human distal humeri. Thus, an archaic/modern human dichotomy-as previously reported for proximal ulnar morphology-is not supported with respect to distal humeral morphology. Relative to australopiths and modern humans, Neandertal humeri are characterized by large olecranon fossae and small distodorsal medial and lateral pillars. The seeming disparity in morphological affinities of proximal ulnae (in which all archaic human groups appear distinct from modern humans) and distal humeri (in which Neandertals appear distinct from modern humans, but other archaic humans do not) is probably indicative of a highly variable, possibly transitional population of which our knowledge is hampered by sample-size limitations imposed by the scarcity of middle-to-late Pleistocene premodern human fossils outside of Europe.     

Introgression of Neandertal- and Denisovan-like Haplotypes Contributes to Adaptive Variation in Human Toll-like Receptors

Pathogens and the diseases they cause have been among the most important selective forces experienced by humans during their evolutionary history. Although adaptive alleles generally arise by mutation, introgression can also be a valuable source of beneficial alleles. Archaic humans, who lived in Europe and Western Asia for more than 200,000 years, were probably well adapted to this environment and its local pathogens. It is therefore conceivable that modern humans entering Europe and Western Asia who admixed with them obtained a substantial immune advantage from the introgression of archaic alleles. Here we document a cluster of three Toll-like receptors (TLR6-TLR1-TLR10) in modern humans that carries three distinct archaic haplotypes, indicating repeated introgression from archaic humans. Two of these haplotypes are most similar to the Neandertal genome, and the third haplotype is most similar to the Denisovan genome. The Toll-like receptors are key components of innate immunity and provide an important first line of immune defense against bacteria, fungi, and parasites. The unusually high allele frequencies and unexpected levels of population differentiation indicate that there has been local positive selection on multiple haplotypes at this locus. We show that the introgressed alleles have clear functional effects in modern humans; archaic-like alleles underlie differences in the expression of the TLR genes and are associated with reduced microbial resistance and increased allergic disease in large cohorts. This provides strong evidence for recurrent adaptive introgression at the TLR6-TLR1-TLR10 locus, resulting in differences in disease phenotypes in modern humans.     

尼安德特人基因组学研究进展

尼安德特人是现代人最近的旁支,也是化石资料最丰富的古人类。在现代人起源问题的争论中,尼安德特人对现代人是否有遗传贡献是一个焦点问题。文章综述了近年来关于尼安德特人线粒体基因组和核基因组的研究进展,初步研究表明尼安德特人可能对现代人有遗传贡献,这引发了人们对现代人起源问题的重新思考。藉尼人基因组研究经验进行的古人类基因组学研究将有望揭开现代人起源的谜团,并丰富进化生物学相关领域的理论体系。     

Dental tissue proportions and enamel thickness in Neandertal and modern human molars

The thickness of dental enamel is often discussed in paleoanthropological literature, particularly with regard to differences in growth, health, and diet between Neandertals and modern humans. Paleoanthropologists employ enamel thickness in paleodietary and taxonomic studies regarding earlier hominins, but variation in enamel thickness within the genus Homo has not been thoroughly explored despite its potential to discriminate species and its relevance to studies of growth and development. Radiographic two-dimensional studies indicate that Neandertal molar enamel is thin relative to the thick enamel of modern humans, although such methods have limited accuracy. Here we show that, measured via accurate high-resolution microtomographic imaging, Neandertal molar enamel is absolutely and relatively thinner than modern human enamel at most molar positions. However, this difference relates to the ratio of coronal dentine volume to total crown volume, rather than the quantity of enamel per se. The absolute volume of Neandertal molar enamel is similar to that of modern humans, but Neandertal enamel is deposited over a larger volume of coronal dentine, resulting in lower average (and relative) enamel thickness values. Sample sizes do not permit rigorous intragroup comparisons, but Neandertal molar tissue proportions evince less variation than the modern human sample. Differences in three- and two-dimensional enamel thickness data describing Neandertal molars may be explained by dimensional reduction. Although molar tissue proportions distinguish Neanderthals from recent Homo sapiens, additional study is necessary to assess trends in tissue proportions in the genus Homo throughout the Pleistocene.     

中更新世晚期中国古人类化石的形态多样性及其演化意义

近年对许家窑、许昌、华龙洞、澎湖、夏河、哈尔滨等人类化石开展的系统研究,引发了学界对中更新世晚期人类演化及分类的不同认识。基于对相关中国人类化石形态特征的分析,作者提出这一时期中国人类化石形态特征表现为四种类型：1）以中更新世晚期人类共有特征为主;2）以原始特征为主;3）以现代特征为主;4）独特形态组合。多数化石形态特征表现为前三种类型,而许昌和许家窑这种以硕大的头骨和巨大颅容量构成的独特形态组合在其他同时期化石还没有发现。化石形态的多样性提示,不同类型的中更新世晚期中国古人类对现代人的形成贡献不同。作者认为在该时期的人类化石形态多样性规律还未阐明的情况下,将具有混合或镶嵌特征的相关人类化石归入分类地位不确定的人群较为合适。     

Searching for signatures of cold adaptations in modern and archaic humans: hints from the brown adipose tissue genes

Adaptation to low temperatures has been reasonably developed in the human species during the colonization of the Eurasian landmass subsequent to Out of Africa migrations of anatomically modern humans. In addition to morphological and cultural changes, also metabolic ones are supposed to have favored human isolation from cold and body heat production and this can be hypothesized also for most Neandertal and at least for some Denisovan populations, which lived in geographical areas that strongly experienced the last glacial period. Modulation of non-shivering thermogenesis, for which adipocytes belonging to the brown adipose tissue are the most specialized cells, might have driven these metabolic adaptations. To perform an exploratory analysis aimed at looking into this hypothesis, variation at 28 genes involved in such functional pathway was investigated in modern populations from different climate zones, as well as in Neandertal and Denisovan genomes. Patterns of variation at the LEPR gene, strongly related to increased heat dissipation by mitochondria, appeared to have been shaped by positive selection in modern East Asians, but not in Europeans. Moreover, a single potentially cold-adapted LEPR allele, different from the supposed adaptive one identified in Homo sapiens, was found also in Neandertal and Denisovan genomes. These findings suggest that independent mechanisms for cold adaptations might have been developed in different non-African human groups, as well as that the evolution of possible enhanced thermal efficiency in Neandertals and in some Denisovan populations has plausibly entailed significant changes also in other functional pathways than in the examined one.     

A Hominin Femur with Archaic Affinities from the Late Pleistocene of Southwest China

The number of Late Pleistocene hominin species and the timing of their extinction are issues receiving renewed attention following genomic evidence for interbreeding between the ancestors of some living humans and archaic taxa. Yet, major gaps in the fossil record and uncertainties surrounding the age of key fossils have meant that these questions remain poorly understood. Here we describe and compare a highly unusual femur from Late Pleistocene sediments at Maludong (Yunnan), Southwest China, recovered along with cranial remains that exhibit a mixture of anatomically modern human and archaic traits. Our studies show that the Maludong femur has affinities to archaic hominins, especially Lower Pleistocene femora. However, the scarcity of later Middle and Late Pleistocene archaic remains in East Asia makes an assessment of systematically relevant character states difficult, warranting caution in assigning the specimen to a species at this time. The Maludong fossil probably samples an archaic population that survived until around 14,000 years ago in the biogeographically complex region of Southwest China.     

Neanderthal and Denisova genetic affinities with contemporary humans: Introgression versus common ancestral polymorphisms

Analyses of the genetic relationships among modern humans, Neanderthals and Denisovans have suggested that 1–4% of the non-Sub-Saharan African gene pool may be Neanderthal derived, while 6–8% of the Melanesian gene pool may be the product of admixture between the Denisovans and the direct ancestors of Melanesians. In the present study, we analyzed single nucleotide polymorphism (SNP) diversity among a worldwide collection of contemporary human populations with respect to the genetic constitution of these two archaic hominins and Pan troglodytes (chimpanzee). We partitioned SNPs into subsets, including those that are derived in both archaic lineages, those that are ancestral in both archaic lineages and those that are only derived in one archaic lineage. By doing this, we have conducted separate examinations of subsets of mutations with higher probabilities of divergent phylogenetic origins. While previous investigations have excluded SNPs from common ancestors in principal component analyses, we included common ancestral SNPs in our analyses to visualize the relative placement of the Neanderthal and Denisova among human populations. To assess the genetic similarities among the various hominin lineages, we performed genetic structure analyses to provide a comparison of genetic patterns found within contemporary human genomes that may have archaic or common ancestral roots. Our results indicate that 3.6% of the Neanderthal genome is shared with roughly 65.4% of the average European gene pool, which clinally diminishes with distance from Europe. Our results suggest that Neanderthal genetic associations with contemporary non-Sub-Saharan African populations, as well as the genetic affinities observed between Denisovans and Melanesians most likely result from the retention of ancient mutations in these populations.     

Learning about human population history from ancient and modern genomes

Genome-wide data, both from SNP arrays and from complete genome sequencing, are becoming increasingly abundant and are now even available from extinct hominins. These data are providing new insights into population history; in particular, when combined with model-based analytical approaches, genome-wide data allow direct testing of hypotheses about population history. For example, genome-wide data from both contemporary populations and extinct hominins strongly support a single dispersal of modern humans from Africa, followed by two archaic admixture events: one with Neanderthals somewhere outside Africa and a second with Denisovans that (so far) has only been detected in New Guinea. These new developments promise to reveal new stories about human population history, without having to resort to storytelling.     

Long-range regulation is a major driving force in maintaining genome integrity

Background  

The availability of newly sequenced vertebrate genomes, along with more efficient and accurate alignment algorithms, have enabled the expansion of the field of comparative genomics. Large-scale genome rearrangement events modify the order of genes and non-coding conserved regions on chromosomes. While certain large genomic regions have remained intact over much of vertebrate evolution, others appear to be hotspots for genomic breakpoints. The cause of the non-uniformity of breakpoints that occurred during vertebrate evolution is poorly understood.     

Theoretical and Applied Aspects of Comparative Genomics of Vertebrates

The Human Genome Project stimulated the development of efficient strategies and relevant hardware for complete genome sequencing. The comparative genomic approach extends the possibilities of using the sequencing data to identify new genes or conserved regulatory regions by means of nucleotide sequence alignment of the particular regions of the mouse and human genomes, or to trace the evolutionary events resulting in the genome structure of modern mammals. The review focuses on the use of new molecular cytogenetic methods along with computer-aided analysis of the genomes in vertebrates. Several factors hindering data analysis are considered. The currently available information on gene evolution rate inferred from comparative genomic data is presented. The origin and evolution of the genomes of several species are discussed.