Genetic admixture in the Late Pleistocene

The replacement hypothesis of modern human origins holds that the original population of modern humans expanded throughout the world, replacing existing archaic populations as it went. If this expanding population interbred with the peoples it replaced, then some archaic mitochondria might have been introduced into the early modern gene pool. Such mitochondria would be recognizable today because they should differ from other modern mitochondria at several times the number of sites that we are used to seeing in pairwise comparisons. In this paper we ask what can be inferred from the absence of these “divergent” mitochondria from modern samples. We show that if the effective number of females in our species has been large for the past 40,000 years, then the level of admixture must have been low. For example, if this effective number exceeded 1.6 million, then we can reject the hypothesis that more more than 2/1,000 of the mitochondria in the early modern population derived from admixture with archaic peoples. We argue elsewhere that regional continuity would be detectable in the fossil record only if the rate of admixture exceeded 76%. Here, we show that this level of admixture would require the effective female size of the human population to have been less than 1,777 for the past 40,000 years. © 1996 Wiley-Liss, Inc.     

Testing for ancient admixture between closely related populations

One enduring question in evolutionary biology is the extent of archaic admixture in the genomes of present-day populations. In this paper, we present a test for ancient admixture that exploits the asymmetry in the frequencies of the two nonconcordant gene trees in a three-population tree. This test was first applied to detect interbreeding between Neandertals and modern humans. We derive the analytic expectation of a test statistic, called the D statistic, which is sensitive to asymmetry under alternative demographic scenarios. We show that the D statistic is insensitive to some demographic assumptions such as ancestral population sizes and requires only the assumption that the ancestral populations were randomly mating. An important aspect of D statistics is that they can be used to detect archaic admixture even when no archaic sample is available. We explore the effect of sequencing error on the false-positive rate of the test for admixture, and we show how to estimate the proportion of archaic ancestry in the genomes of present-day populations. We also investigate a model of subdivision in ancestral populations that can result in D statistics that indicate recent admixture.     

史前古人类之间的基因交流及对当今现代人的影响

古DNA实验技术及高通量测序技术的出现和发展,使得直接从古老化石中进行遗传物质的提取及测序成为可能,与古人类相关的基因组学研究因此取得了一系列突破性进展,已灭绝的古老型人类(如:尼安德特人和丹尼索瓦人)与非洲以外现代人之间基因的相互影响已被诸多证据所证实。研究表明,在史前时期,早期现代人向非洲以外地区扩散时,遭遇到了现已灭绝的古老型人类,他们在同一时空内长期共存,并发生了基因交流,有一部分古老型人类基因因此流向了现代人,有些基因一直流传至今,对当今现代人的基因组成产生重大影响;此外,不同古老型人类之间也存在基因交流;而早期现代人也对部分古老型人类的基因组成造成了影响。化石与古DNA信息的证据均表明,史前各种人类之间的基因交流在多个地区发生多次,他们的基因交流共同构建了当今现代人的基因库,并在生理机能、形态和疾病发生率等方面对现代人造成了深远的影响。     

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.     

Analysis of human accelerated DNA regions using archaic hominin genomes

Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations.     

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.     

Global genetic variation at OAS1 provides evidence of archaic admixture in Melanesian populations

Recent analysis of DNA extracted from two Eurasian forms of archaic human shows that more genetic variants are shared with humans currently living in Eurasia than with anatomically modern humans in sub-Saharan Africa. Although these genome-wide average measures of genetic similarity are consistent with the hypothesis of archaic admixture in Eurasia, analyses of individual loci exhibiting the signal of archaic introgression are needed to test alternative hypotheses and investigate the admixture process. Here, we provide a detailed sequence analysis of the innate immune gene OAS1, a locus with a divergent Melanesian haplotype that is very similar to the Denisova sequence from the Altai region of Siberia. We resequenced a 7-kb region encompassing the OAS1 gene in 88 individuals from six Old World populations (San, Biaka, Mandenka, French Basque, Han Chinese, and Papua New Guineans) and discovered previously unknown and ancient genetic variation. The 5' region of this gene has unusual patterns of diversity, including 1) higher levels of nucleotide diversity in Papuans than in sub-Saharan Africans, 2) very deep ancestry with an estimated time to the most recent common ancestor of >3 myr, and 3) a basal branching pattern with Papuan individuals on either side of the rooted network. A global geographic survey of >1,500 individuals showed that the divergent Papuan haplotype is nearly restricted to populations from eastern Indonesia and Melanesia. Polymorphic sites within this haplotype are shared with the draft Denisova genome over a span of ～90 kb and are associated with an extended block of linkage disequilibrium, supporting the hypothesis that this haplotype introgressed from an archaic source that likely lived in Eurasia.     

Possible ancestral structure in human populations

Determining the evolutionary relationships between fossil hominid groups such as Neanderthals and modern humans has been a question of enduring interest in human evolutionary genetics. Here we present a new method for addressing whether archaic human groups contributed to the modern gene pool (called ancient admixture), using the patterns of variation in contemporary human populations. Our method improves on previous work by explicitly accounting for recent population history before performing the analyses. Using sequence data from the Environmental Genome Project, we find strong evidence for ancient admixture in both a European and a West African population (p ≈ 10⁻⁷), with contributions to the modern gene pool of at least 5%. While Neanderthals form an obvious archaic source population candidate in Europe, there is not yet a clear source population candidate in West Africa.     

African human diversity, origins and migrations

The continent of Africa is thought to be the site of origin of all modern humans and is the more recent origin of millions of African Americans. Although Africa has the highest levels of human genetic diversity both within and between populations, it is under-represented in studies of human genetics. Recent advances have been made in understanding the origins of modern humans within Africa, the rate of adaptations due to positive selection, the routes taken in the first migrations of modern humans out of Africa, and the degree of admixture with archaic populations. Africa is also in dire need of effective medical interventions, and studies of genetic variation in Africans will shed light on the genetic basis of diseases and resistance to infectious diseases. Thus, we have tremendous potential to learn about human variation and evolutionary history and to positively impact human health care from studies of genetic diversity in Africa.     

Modern Human Origins in the Levant and Western Asia: The Fossil and Archeological Evidence

Upper Pleistocene human fossil and archeological evidence from the Levant and western Asia indicates continuity over the Middle/Upper Paleolithic transition and the transition from archaic to modern Homo sapiens. It also indicates that these transitions did not coincide with each other in time. Both data sets are examined in light of recent claims from molecular biology invoked by replacement advocates in support of the position that morphologically modern humans develop (or arrive) first in the Levant, coexist with archaic Homo sapiens, and then displace or extirpate archaic Homo sapiens. Replacement models that assume no admixture are not supported by the archeological or the human paleontological evidence. Those who would argue for replacement without gene flow must show how it could have occurred without leaving traces of disjunction in the typological and technological aspects of Levantine archeological assemblages, in those aspects of the archeofaunal record that monitor subsistence, and in the evidence from settlement pattern studies.     

Has the combination of genetic and fossil evidence solved the riddle of modern human origins?

Debate over the origin of modern humans continues without a clear end in sight. Currently, the genetic and fossil evidence is still used to support two different interpretations of the origin of modern humans. Some researchers claim that the genetic evidence is compatible with either an Out‐of‐Africa or a Multiregional model, while other scientists argue that the evidence supports only a Multiregional model of evolution. I argue that the fossil record and archeological evidence constrain interpretation of the genetic evidence and imply that very little, if any, admixture with Eurasian archaic hominins such as the Neanderthals occurred during the spread of modern humans out of Africa.     

中国现代人起源与演化的考古学思考

越来越多古人类学和旧石器时代考古学的发现与研究成果极大地改变了我们对现代人类起源、演化和适应理论问题的看法。中国作为东亚一个幅员辽阔的地理区域,已经成为这项研究的热点地带。来自该地区新的人类化石和石器组合对基于非洲和欧亚大陆西部记录构建的“现代人出自非洲说”（Recent Out-of-Africa）提出了挑战。新的古人类学研究结果表明,早期现代人出现于约100 kaBP的中国南方,可能（至少部分）是由那里的土著居民演化而来。一些古老型智人表现出了与早期古人类镶嵌或过渡性的体质特征,并可能与尼安德特人和丹尼索瓦人杂交混合。同时一些遗址出土的打制石器表现出了早期现代人类技术和行为的复杂性。中国北方的小石片石器主工业和南方的砾石石器主工业贯穿于整个更新世,然而从约40 kaBP开始,石叶技术开始出现在中国北部,紧随其后的是这些地区骨制工具和个人装饰品的出现,这表明,更新世晚期西伯利亚和中亚地区与我国北部可能存在着紧密的文化关系,东北亚地区可能存在着由西北向东南的迁移路线。人类化石和考古学证据表明,中国现代人类起源和适应的过程与机制可能与欧亚大陆西部有所不同。本文对有关中国现代人类起源与演化的考古学研究所取得的新发现和进展进行了总体回顾,从考古学角度阐述了对相关重要学术问题的看法,并为未来的研究提出了方向性建议。     

The archeology of modern human origins

Two competing hypotheses have long dominated specialist thinking on modern human origins. The first posits that modern people emerged in a limited area and spread from there to replace archaic people elsewhere. Proponents of this view currently favor Africa as the modern human birthplace.^1–5 The second suggests that the evolution of modern humans was not geographically restricted, but invlved substantial continuity between archaic and modern populations in all major regions of the occupied world.^6–7 Based solely on the fossil record, both hypotheses are equally defensible, but the spread-and-replationships scenario is far more strongly supported by burgeoning data on the genetic relationships and diversity of living humans.^8–16 These data impy that there was a common ancestor for all living humans in Africa between 280,000 and 140,000 year ago, and that Neanderthals and other archaic humans who inhabited Eurasia during the same interval contributed few, if any, genes to living peiple. I argue here that the spread-and-replacement hypothesis is also more compatible with a third line of evidence: the spread-and-replacement hypothesis is also more compatible with a third line of evidence: the archeological record for human behavioral evolution.     

Olduvai Hominid 7 trapezial metacarpal 1 articular morphology: contrasts with recent humans

A consideration of the metacarpal 1 articulation of the Olduvai Hominid 7 trapezium shows that, although it is generally similar to those of recent humans, it is considerably flatter radioulnarly and dorsopalmarly than those of modern humans and similar in its degree of dorsopalmar flattening to those of Upper Pleistocene late archaic humans. Even though this flattening may have slightly limited flexion-extension at the pollical carpometacarpal joint, it is most likely related to the apparently elevated levels of axial joint reaction force through the thumbs of archaic members of the genus Homo. It also documents the continuation of human carpometacarpal articular evolution through the Pleistocene.     

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.     

Testing for archaic hominin admixture on the X chromosome: model likelihoods for the modern human RRM2P4 region from summaries of genealogical topology under the structured coalescent

A 2.4-kb stretch within the RRM2P4 region of the X chromosome, previously sequenced in a sample of 41 globally distributed humans, displayed both an ancient time to the most recent common ancestor (e.g., a TMRCA of approximately 2 million years) and a basal clade composed entirely of Asian sequences. This pattern was interpreted to reflect a history of introgressive hybridization from archaic hominins (most likely Asian Homo erectus) into the anatomically modern human genome. Here, we address this hypothesis by resequencing the 2.4-kb RRM2P4 region in 131 African and 122 non-African individuals and by extending the length of sequence in a window of 16.5 kb encompassing the RRM2P4 pseudogene in a subset of 90 individuals. We find that both the ancient TMRCA and the skew in non-African representation in one of the basal clades are essentially limited to the central 2.4-kb region. We define a new summary statistic called the minimum clade proportion (pmc), which quantifies the proportion of individuals from a specified geographic region in each of the two basal clades of a binary gene tree, and then employ coalescent simulations to assess the likelihood of the observed central RRM2P4 genealogy under two alternative views of human evolutionary history: recent African replacement (RAR) and archaic admixture (AA). A molecular-clock-based TMRCA estimate of 2.33 million years is a statistical outlier under the RAR model; however, the large variance associated with this estimate makes it difficult to distinguish the predictions of the human origins models tested here. The pmc summary statistic, which has improved power with larger samples of chromosomes, yields values that are significantly unlikely under the RAR model and fit expectations better under a range of archaic admixture scenarios.     

中更新世非洲Bodo人类头骨化石与周口店直立人的比较--中国与非洲人类头骨特征对比之三

发现于埃塞俄比亚MiddleAwash地区Bodo地点距今60万年的人类头骨化石是迄今发现的最为古老和完整的非洲中更新世人类化石。由于Bodo头骨化石在形态特征上兼有直立人与智人的特点,多年来学术界对其分类地位一直存在争议。Rightmire认为Bodo头骨化石与BrokenHill及Petralona等在分类上属于古老型智人的中更新世人类更为接近,是非洲直立人向古老型智人过渡的代表。至少在距今60万年的中更新世早期直立人向古老型智人转变的成种事件在非洲就已经发生。以Bodo头骨为代表的一批更新世中期非洲和欧洲人类化石构成了可能是后期人类祖先的人属海德堡种。这些观点导致了近年学术界对古老型智人在非洲及欧亚出现时间以及更新世中期非洲和欧亚地区古人类相互之间演化关系的关注。基于这样的背景,本文对年代与Bodo化石接近的周口店直立人头骨特征与Bodo头骨的相似及差异表现情况进行了对比研究。结果发现Bodo头骨在一系列特征上与周口店直立人相似,同时在包括颅容量在内的其它一些特征上呈现出后期智人的特点,但总体形态上似乎与直立人更为相似。作者认为尽管这种进化上的镶嵌现象在中国古人类化石记录上也广泛存在,但由于中国人类化石标本在年代上的不确定性,目前还没有可靠的证据说明这种集直立人与智人化石特征为一体的镶嵌性在中国古人类化石出现的时间接近或早于非洲。考虑到中国与非洲直立人生存年代的巨大差异及人类演化的不同步或地区间差异,具有较多后期人类特征表现的人类首先出现在非洲是完全可能的。根据这些研究对比,作者就人类演化的镶嵌现象、更新世中期非洲与亚洲地区人类演化上的差异等问题进行了讨论。     

更新世中期中国古人类演化区域连续性与多样性的化石证据

以往,在东亚大陆发现的更新世中期人类化石被分别归入直立人和古老型智人。这种分类的主要依据是化石形态特征以及年代。魏敦瑞对周口店第一地点人类化石研究描述的一些头骨、下颌骨和牙齿特征通常被作为判定直立人的标准。根据这些化石的年代分布,一般将30万年前的中更新世晚期作为划分直立人与古老型智人的大致年代界限。近20年来,在非洲、欧洲和东亚新发现了一些更新世中期人类化石,目前古人类学界对中国更新世中期人类化石特征及演化有了与以往不同的认识。最近对大荔、许家窑、盘县大洞、许昌、华龙洞等人类化石的研究显示,近30万年以来东亚大陆人类演化呈现复杂的多样性,将这一时期人类全部归入古老型智人难以准确反映更新世中期中国古人类演化模式及规律。本文结合近年中国更新世中期人类演化研究进展,选择部分具有演化及分类价值的形态特征,分析这些特征在更新世中期中国古人类化石的表现特点。在此基础上,对更新世中期中国古人类演化模式做了尝试性探讨。本研究发现,周口店、和县、沂源、南京等中更新世早期人类化石呈现有较多的区域性特征,形态特征表现相对稳定;而大荔、金牛山、许家窑、许昌、华龙洞、马坝、盘县大洞等中更新世晚期人类在化石形态特征表现复杂多样,变异范围大。此外,在这一时期人类化石上发现较多与生存活动、健康、环境适应有关的证据。根据这些发现,作者认为中国中更新世早期组人类演化以形态连续性为主;进入中更新世晚期,中国古人类演化区域性特征减弱,演化模式以多样性为主。一系列新的化石发现和研究证据提示中更新世晚期东亚大陆可能生存有不同的古人类成员。根据目前掌握的化石形态和年代证据,大约30万年前是中国更新世中期演化变化关键时间节点。     

新证据下的现代人起源模型

解剖结构上的现代人是指具有近圆球形头骨、短而平的面颅、纤细的骨骼等特征的区别于其他古老人类的化石和现今的人群。支持多地区演化模型和支持近期非洲起源模型的学者,在“解剖结构上的现代人”的应用范围方面是不同的,前者以连续演化为基本思想,认为这一名词只包括智人中较进步的类群;而后者以分支系统学思想为基础,认为包括所有智人。分子古生物学研究显示,尼人、丹人和智人在遗传学水平上属于不同的人种。新近的以标本-种群为单元的系统分析,因为不是以属、种等分类学阶元进行的,因此与分类学的阶元划分无关。该系统分析的结果显示智人属于单系类群,哈尔滨人、大荔人等组成其姊妹群。尼人与智人的分异早于1百万年,与基因组水平的谱系分析相符合。多次多向的穿梭扩散是统计学上符合系统关系的模型。