古人类基因组与健康

随着第二代测序技术的发展,古人类基因组的研究进展迅速,各个古人类种群的起源与基因流向逐一揭晓,从中找出了对现代人基因有贡献的古人类种群,由此引发了对人类起源的重新思考与探究。更为重要的是古人类基因存在与疾病相关的序列信息,不仅为现代人医疗保健研究提供了参考,还有助于研究现代人疾病的发生。本文就近年来具有代表性的古人类基因组研究成果及其中与健康相关的重要发现作简要介绍。     

沉积物古DNA探秘灭绝古人类演化

古DNA领域首次从世界不同洞穴遗址的沉积物里提取古核基因组以揭示相关物种演化的突破性进展,标志着沉积物古DNA研究正式进入全基因组时代。近期,一种新的沉积物古核DNA富集方法成功从西班牙Estatuas洞穴沉积物里捕获多个尼安德特人的核DNA,揭示该灭绝古人类群体此前未知的人口更替的历史。沉积物古核DNA富集突破了古DNA研究依赖化石材料的限制,为深入探究远古不同人类群体在更宏大时空框架下迁徙、演化与适应的历史提供了更多可能。由此,本文将着重解读该研究带来的对尼安德特人遗传历史的新认识及其方法创新的重要意义;此外还将结合人类化石DNA及其他沉积物研究所发现的灭绝古人类线粒体DNA证据,厘清尼安德特人的种群多样性及其种群间分离或替代的历史。     

基于DNA分子的现代人起源研究35年回顾与展望

1983年,有学者首次发表现代人线粒体DNA进化树,认为现代人可能起源自亚洲。1987年,又有学者按照分子钟假说得到线粒体在10-20万年前出自非洲的推论。随后,以分子钟为前提的Y染色体和常染色体DNA研究也支持了出非洲的结论,该结论逐渐成为分子进化领域的主流理论。2010年,对尼安德特人常染色体基因组的研究指出其对现代人有遗传贡献,这颠覆了人们先前关于现代人只来源自非洲,其他大洲的当地古人被完全取代的认知。目前,单地区起源说已经被修正为同化说。尽管学界对非洲人遗传多样性最高这一现象有共识,但是对该现象的不同解读却可以得出两种迥然不同的结果,现代人出亚洲说和出非洲说。大量研究证实基因组的大部分序列是有功能的,并处在遗传变异水平的饱和态,这质疑了中性理论以及由它推导的现代人出非洲说的合理性,而中性理论的提出恰恰是用来解释并非普遍存在的分子钟的。近年来已经有研究者从新理论的角度解读遗传多样性的饱和态和线性态,人们对现代人起源的认识将会进一步加深完善。     

辽宁建平古人类肱骨形态结构分析

1957年,在辽宁省建平县发现了一根古人类肱骨化石,编号PA103。通过同一批龙骨中筛选的哺乳动物化石,吴汝康推断PA103应该为更新世晚期古人类,并对该化石进行了表面形态特征观察和描述。为了对PA103化石的内外结构进行更全面的了解,除了线性测量数据的对比,本文还通过计算机断层扫描技术,结合生物力学和形态示量图分析对建平古人类右侧肱骨化石PA103进行了分析。通过本研究发现,PA103骨干横断面的生物力学粗壮度和力学形状指数明显小于尼安德特人,而与同时期欧亚大陆古人类不利手侧最为接近,这说明建平人右侧肱骨可能不是惯用手,同时,建平人的行为活动应该与同时期同地区的古人类处于同一水平,而小于尼安德特人。整体来看,PA103骨干骨密质厚度和截面惯性矩与近现代人的分布模式较为接近,除局部数值增大外,其整体数值小于近现代人的平均水平,这可能与遗传或行为活动有关,由于缺少古人类化石对比数据,更详细的了解还需后期开展更多相关的研究。     

名刊封面

《细胞》2008.8尼安德特人线粒体基因组问世高通量454测序技术被广泛应用于分析古代DNA样本,为复原古代DNA提供了可能。近日,来自德国、美国、克罗地亚和芬兰的科学家发表了他们的最新研究结果,通过454测序技术,科学家得到了一个尼安德特个体的完整线粒体DNA基因组序列。尽管科学家相信尼安德特人是最接近现代人类的原始人种,但是关于他们与现代人类之间的精确关系却一直存在争论。     

远古的馈赠：近现代人类基因溯源突破性进展写在2022年诺贝尔生理学或医学奖颁布之际

2022年诺贝尔生理学或医学奖授予瑞典生物学家斯万特·帕博（Svante P??bo）,以表彰他在古人类基因组学和人类起源方面做出的决定性贡献。关于人类起源,存在各种学说,目前主流的观点是“走出非洲学说”。斯万特·帕博在开创一门新的学科——古人类基因组学的同时,一直在不断完善“走出非洲学说”。他借助各种生物学技术,从基因组学的角度去深入探究人类起源,发现我们身体内保留着一些来自古人类的基因印迹。这项研究意味着在研究某些疾病的时候可以追根溯源,而不是将眼光局限于基因本身,探究某个基因从哪里来将会是研究疾病的全新思路。本文总结了他在研究过程中对相关生物技术的革新、基于线粒体和核基因组对古人类的探究以及相关成果,并介绍了一些源自古人类的基因及其有关信息。     

中国人类遗传多样性研究进展

人类遗传多样性表现为世界各种族、民族和个体间存在的基因组差异,是探讨人类进化与迁徙、环境与遗传背景相互作用、疾病与健康影响因素的主要资源和工具。中国具有世界1/5的人口,有56个民族和丰富的遗传多样性资源。经过几十年的努力,中国人类遗传多样性研究已积累了丰富的资料,部分成果已经达到国际先进水平。文章重点论述了近年来形态学标记、生化及免疫学标记、DNA遗传标记在我国人类遗传多样性研究中的应用,线粒体DNA、Y染色体DNA和HLA标记在中国不同民族源流和相互关系、东亚现代人起源和迁移等研究中的应用,以及我国在中华民族遗传资源保存和利用、疾病易感基因和环境适应相关基因的鉴定及全基因组关联分析和第二代测序技术的应用、中国人基因组结构研究等方面取得的重要成果和进展。     

山东新泰乌珠台人类牙齿的形态学特征

近些年在东亚发现的晚更新世现代人化石及其研究使得关于该地区现代人起源问题更加复杂,更多该时段人类标本的研究有助于对其有更清晰的认识。1966年在山东新泰乌珠台发现一枚古人类下颌臼齿,吴新智和宗冠福(1973)对其进行了报道,而后再无详细研究。本文将使用牙齿非测量性状的半定量化(分级)、齿冠外轮廓形状的几何形态测量、基于显微断层扫描(Micro-computed tomography 或micro-CT)的釉质厚度、釉质厚度分布规律和齿质表面三维结构复原等方法对乌珠台人类牙齿进行综合研究,进而对东亚晚更新世古人类牙齿形态特征变异有一个进一步的了解。结果显示,乌珠台人类牙齿的形态特征基本与现代人接近,但其所表现出的三角座横脊、Y型齿沟排列、原附尖在现代人中出现率较低,而更多发现在直立人或尼安德特人中。相对于东亚其他晚更新世现代人,乌珠台M3所表现出的特征组合具有特殊性,增加了东亚晚更新世现代人的牙齿形态特征多样性。未来研究可尝试测定乌珠台人类牙齿的绝对年代,以更好的将其归入到现代人演化序列中去。     

人类起源的发现史

最早的古人类化石在达尔文提出进化论之前已经出土了,随后新的化石不断发现,到现在为止,人们已经能根据化石大体勾画出从猿到人的进化脉络了。在这些古人类化石中,有些当时就引起了轰动,有些虽然在发现的时候没有引起重视,但是后来的发现确定了其重要的地位。1856年,在德国尼安德特谷的一个洞穴中发现了一块古人类头骨和若干体骨的化石,这是古人类化石的第一个重要发现。     

东亚现代人来源的考古学思考:证据与解释

现代人的起源与扩散是当今古人类学界极具争议的问题。目前,"多地区进化"假说和非洲起源为主的"同化"假说是该争议的两大阵营。在"多地区进化"假说的基础上,立足中国的化石材料,吴新智提出了中国乃至东亚古人类"连续演化、附带杂交"的假说,认为中国的现代人主要由本地古老类型人类演化而来。本文从现代人扩散关键时段的考古材料出发,讨论氧同位素5～3阶段(大约13～3万年)考古材料在研究中国现代人形成中的作用和存在的挑战。首先,概括介绍现代人起源的主要假说和现代人扩散的假定路线——南线和北线的多重证据;其次,在此背景下,通过对中国境内考古材料的概括,分析不同石器技术可能反映的现代人来源;最后,简要探讨立足考古材料研究现代人起源与扩散的挑战。总体而言,氧同位素5～3阶段的旧石器考古材料支持中国北方南部和中国南方古人类的连续演化,同时也指示了非洲扩散而出的现代人人群自西北地区和南方地区进入中国的可能性。该模式支持中国古人类"连续演化、附带杂交"假说,然而我们也认识到中国现代人起源研究的考古基础仍十分薄弱,使用考古学材料研究现代人扩散的理论基础也需探讨。目前,细化、完善基础考古数据仍是中国旧石器时代考古学和古人类学学者努力的主要方向之一。如此,我们才能够更加有效地将人类化石与考古学证据融合,进而结合分子生物学的研究,更为全面地理解现代人的起源与演化。     

Chin morphology and sexual dimorphism in the fossil hominid mandible sample from Klasies River Mouth

The site of Klasies River Mouth (KRM) in South Africa has produced a small sample of early Upper Pleistocene hominid remains that have been a focus for discussions of the origins of modern humans. Despite certain primitive characteristics exhibited by these fossils, proponents of a single recent origin have attributed them to early modern humans. Critics of this hypothesis have emphasized the significance of the archaic features evident in this sample, including the absence of pronounced chins among the mandibular specimens. This study compares the size range and chin morphology exhibited by the KRM mandibles with that of Neandertals, Upper Pleistocene humans, and recent humans. The extreme sexual dimorphism documented among the KRM fossils reflects the presence of a very small individual, and previous efforts to classify the KRM sample as archaic on the basis of their robusticity have failed to address the significance of this diminutive hominid. While each KRM fossil falls within the 95% envelope of variability established for chin development in a comparative modern sample, a similarly low frequency of pronounced chins is very unlikely to be found in any recent human population. The morphological pattern of the KRM mandibles is clearly distinct from that of Neandertals and of recent humans. © 1996 Wiley-Liss, Inc.     

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.     

Late archaic and modern Homo sapiens from Europe, Africa, and Southwest Asia: Craniometric comparisons and phylogenetic implications

The craniometric affinities among Neandertals. Upper Palcolithic Europeans, early anatomically modern Southwest Asians, and archaic and modern Africans are investigated using univariate and multivariate methods. For the first time, it is possible to analyse the North African finds Dar-es-Soltane 5, Nazlet Khater, and Wadi Kubbaniya. It was not possible to include the Neandertals from Central Europe due to their poor state of preservation. The results point to, first, a basic distinction between Neandertals on the one hand and modern humans from all geographic regions on the other, and, secondly, to great similarities between modern African and European populations. Late archaic sapiens specimens from Africa were more similar to Upper Paleolithic Europeans than were the Neandertals. The results do not support the hypothesis that a regional evolution giving rise to modern humans took place in Europe. The results are, however, consistent with the hypothesis that modern populations originated in Africa and spread to Europe from there.     

Postcranial remains and the origin of modern humans

The nature, timing, and location of the origin of modern humans has been the subject of intense controversy for the last 15 years.^1–4 Genetic data and new radiometric dates for key fossils that lie beyond the range of radiocarbon dating have substantially added to the knowledge derived from the fossil evidence documenting the transition from archaic to modern humans. These new data, however, have failed to resolve the problem in its entirety. Most authorities now accept that Africa played an important, and probably central, role in the origin of modern humans.^7–13 The genetic evidence seems to be particularly emphatic that an African population that existed between 200,000 and 100,000 years ago (100 ka) is ancestral to all living humans.^6,7 Controversy still surrounds the question of how much, if at all, archaic humans from outside of Africa, such as Neandertals, late archaic Chinese hominins such as Jinniushan, and the Indonesian Ngandong hominins, may have contributed to the morphological and genetic diversity present in living populations and the morphology of the earliest fossils of modern humans.¹⁰     

No evidence of Neandertal admixture in the mitochondrial genomes of early European modern humans and contemporary Europeans

Neandertals, the archaic human form documented in Eurasia until 29,000 years ago, share no mitochondrial haplotype with modern Europeans. Whether this means that the two groups were reproductively isolated is controversial, and indeed nuclear data have been interpreted as suggesting that they admixed. We explored the range of demographic parameters that may have generated the observed mitochondrial diversity, simulating 3.0 million genealogies under six models differing as for the relationships among contemporary Europeans, Neandertals, and Upper Palaeolithic European early modern humans (EEMH), who coexisted with Neandertals for millennia. We compared by Approximate Bayesian Computations the simulation results with mitochondrial diversity in 7 Neandertals, 3 EEMH, and 150 opportunely chosen modern Europeans. A model of genealogical continuity between EEMH and contemporary Europeans, with no Neandertal contribution, received overwhelming support from the analyses. The maximum degree of Neandertal admixture, under the model of gene flow supported by nuclear data, was estimated at 1.5%, but this model proved 20-32 times less likely than a model without any gene flow. Nuclear and mitochondrial evidence might be reconciled if smaller population sizes led to faster lineage sorting for mitochondrial DNA, and Neandertals shared a longer period of common ancestry with the non-African's than with the African's ancestors.     

Occipital bunning among later pleistocene hominids

Occipital bunning is a posterior projection of the occipital squama, which occurs in varying frequencies in samples of archaic Homo sapiens, Upper Pleistocene anatomically modern humans, and recent humans. It can be best interpreted as a product of the timing of posterior cerebral growth relative to the growth of the cranial vault bones. It is not a feature that was unique to the Neandertals.     

The place of Neandertals in the evolution of hominid patterns of growth and development

This study uses the two developmental fields of dental maturation and femoral growth to determine if the pattern of growth and development in Neandertals (archaic Homo sapiens) was intermediate between that of Homo erectus and recent modern humans. Specimens used in the analysis included Neandertals and Upper Palaeolithic early modern Homo sapiens from Europe and individuals from two recent modern human populations. Ontogenetic data for the H. erectus adolescent KNM-WT 15000 and for Gorilla gorilla were included for comparison. Previous reports have indicated that H. erectus demonstrates a pattern of ontogeny characterized by earlier and more rapid linear growth than in modern humans. Results reported here demonstrate that Upper Paleolithic early modern Homo sapiens display a growth trajectory indistinguishable from that of recent modern humans. The pattern of Neandertal ontogeny is not intermediate between the pattern displayed in H. erectus and the derived pattern seen in the modern reference samples and the early modern H. sapiens sample. The Neandertal growth trajectory is consistent with either slow linear growth or advanced dental development.     

Neandertals: Images of ourselves

During the last two decades, paleoanthropology has focused increasingly on the global issue of modern human origins, and a preeminent part of that process has concerned the fate of the Neandertals of the northwestern Old World. Not so long ago, working on the origins of modern humans was a niche cloaked in convenient obscurity. Many human paleontologists were content to largely ignore, and thus remained ignorant of, the hominid fossils of the later Pleistocene, an attitude parallel to that of Bordes regarding the Neolithic in comparison to the more glamorous Paleolithic; he referred to the former simply as, “C'est de la merde!” However, the Neandertais have become a topic guaranteed to attract attention, thus drawing in scholars who until recently disdained interest in such basically human fossil hominids. They are now willing to direct their students' and even their own research toward late archaic humans (such as Neandertals) and early modern humans in whatever portion of the Old World is most readily available.