古DNA的新发现支持现代人东亚起源说

1983年,科学家们根据线粒体DNA（mtDNA）系统发育树构建了首个现代人起源的分子模型,认为现代人起源于亚洲,但1987年非洲起源说的提出取代了这一亚洲起源说。非洲起源说所依赖的无限多位点假说以及分子钟假说后来被普遍认为是错误的且不切实际的。我们近几年提出了一个新的分子进化模式,即遗传多样性上限理论,重新构建了一个新的人类起源模型。这一模型与多地区起源说基本吻合, 重新把现代人类起源地定位在了东亚。非洲说与东亚说在线粒体进化树上的主要区别是单倍型N和R的关系,非洲起源说认为N是R的祖先,东亚说则反之。本研究引用了已发表的古代人群mtDNA数据,重点分析了线粒体单倍群N和R的关系。结果显示,三个最古老的人类（一个距今45000年,其他两个约40000年）都属于单倍群R;在距今39500到30000年前的人类样本中,绝大部分属于单倍群R下游的亚单倍群U,只有两例为单倍群N（Oase1距今39500年,Salkhit距今34425年）。这两例所属单倍型位于单倍群N下游最基本的未分化亚型,不属于今天存在的任何N下游单倍型,所以可能靠近单倍群N的根部。这些古DNA数据揭示单倍群R比单倍群N古老大约5000年,进一步证实了亚洲起源说的正确性,非洲说的依据不足。     

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。     

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。     

现代人的线粒体DNA起源于非洲

线粒体DNA的进化发展快于细胞核DNA,且纯属母体遗传,故常用作追踪人类DNA起源时间的理想对象。有人推测,现代人的所有的线粒体DNA类型均起源于20万年前的非洲人。这一推测吸引了生物学界的极大注意。最近,美国加州大学柏克莱分校生物化学和分子生物学系的Vigilant等为进一步验证这一设想,从世界各地的189名个体包括121名非洲居民采取了线粒体DNA样品,检测了这些线粒体DNA的2个超变片段的序列,并利用所得到的资料建成一系统树。Vigilant等     

东亚人群源流研究新进展

中国科学家对大量东亚人群样本中分析得到的近200个未定类型的线粒体DNA序列进行研究,结果显示,迄今甄别出来的线粒体DNA未定类型事实上均源自非洲起源的建群类型M或N,没有发现可能追溯至古人类的母系遗传组份。进一步分析还提示,研究中新鉴别的基部类群很可能代表了最初进入东亚南部的现代人群祖先的母系遗存,而非来自邻近地区的近期基因流。     

现代罗布人mtDNA 9bp序列缺失频率与DYS287位点多态性研究

目的:研究现代罗布人线粒体DNA 9bp序列缺失频率与Y染色体DYS287位点多态性.方法:分别采用PCR扩增直接测序法和PCR结合琼脂糖凝胶电泳检测法对不同位点的多态性进行分析.结果:在48名无关现代罗布人群个体中,线粒体DNA9bp序列缺失频率为8.3%,在34名无关现代罗布人群男性个体中DYS287全部显示为YAP-.结论:获得现代罗布人线粒体DNA 9bp序列缺失频率与Y染色体DYS287位点多态性数据,为该群体遗传关系的分析、法医学鉴定及该群体的起源提供了一定的遗传背景资料.     

现代人起源问题的新争论

现代人在分类学上称为晚期智人。他们是怎样起源的?长期来有两种理论,一种叫直接演化说(Direct evolution hypothesis)或系统说,也叫多地区起源说。这种理论认为现代人是由当地的早期智人以至猿人演化而来的,各人种在很久以前即已分歧,各自平行发展,演化成现代人,但长时期来互相有基因的交流。例如欧洲的白种人是由当地的尼安德特人逐渐演变来的;亚洲的黄种人是由当地的早期智人和猿人演变来的。另一种理论叫入侵论(Invasion hypothesis),也叫迁徙说或代替说,这种理论认为欧洲是典型尼人的家乡, 而解剖结构上的现代人是在欧洲以外地区演化出来, 然后侵人欧洲的尼人区域, 消灭了土著的尼人而形成的;侵人亚洲的也一样, 形成现代的黄种人。这种单一地区起源说过去一般认为亚洲西部是现代人最早形成的地区, 近年来有人提出非洲南部才是现代人最早形成的地区, 然后迁徙到世界各地。     

植物线粒体DNA质粒研究进展

本文列出了已发现的高等植物中的线粒体DNA质粒,按分子形状分为线粒体环状DNA质粒和线粒体线状DNA质粒,环状线粒体DNA质粒的特征是分子较小, 序列中有正向/反向重复序列,ORF一般较小。线状线粒体DNA质粒的特征是分子较大,末端有重复序列,5'端与蛋白质共价结合,有较长的ORF。还分别介绍了它们的复制机制、转录和起源。质粒间及质粒与核基因组、线粒体基因组、叶绿体基因组的同源性也作了介绍。最后,综述了植物线粒体DNA质粒与植物的细胞质雄性不育（CMS）之间的关系。     

日本京都举行关于现代人起源的国际讨论会

日本京都举行关于现代人起源的国际讨论会现代人起源问题长期为人们所关注．１９８７年美国加州大学的分子生物学家威尔逊和他的两位学生堪恩和斯通金发表论文,根据他们对现代人线粒体ＤＮＡ的研究,认为所有现代人都可追溯到大约２０万年前非洲的一位妇女．这就是“夏娃...     

中国猕猴遗传多样性研究进展

从形态学、染色体、蛋白质、DNA水平等方面对中国猕猴的遗传多样性进行了综述,以期为我国猕猴资源的保护和利用提供理论基础,为猕猴遗传多样性的研究提供参考.染色体核型和蛋白质分析表明中国猕猴遗传多样性有限,DNA多态性分析表明中国猕猴具有丰富的遗传多样性.基于线粒体控制区部分序列的分析有助于中国猕猴系统发育与进化的研究,Neighbor-joining进化树和Median-Joining网络图将中国猕猴分为7个类群.     

Time of the deepest root for polymorphism in human mitochondrial DNA

Summary A molecular clock analysis was carried out on the nucleotide sequences of parts of the major noncoding region of mitochondrial DNA (mtDNA) from the major geographic populations of humans. Dates of branchings in the mtDNA tree among humans were estimated with an improved maximum likelihood method. Two species of chimpanzees were used as an outgroup, and the mtDNA clock was calibrated by assuming that the chimpanzee/human split occurred 4 million years ago, following our earlier works. A model of homogeneous evolution among sites does not fit well with the data even within hypervariable segments, and hence an additional parameter that represents a proportion of variable sites was introduced. Taking account of this heterogeneity among sites, the date for the deepest root of the mtDNA tree among humans was estimated to be 280,000±50,000 years old (±1 SE), although there remains uncertainty about the constancy of the evolutionary rate among lineages. The evolutionary rate of the most rapidly evolving sites in mtDNA was estimated to be more than 100 times greater than that of a nuclear pseudogene.     

Explaining the Imperfection of the Molecular Clock of Hominid Mitochondria

The molecular clock of mitochondrial DNA has been extensively used to date various genetic events. However, its substitution rate among humans appears to be higher than rates inferred from human-chimpanzee comparisons, limiting the potential of interspecies clock calibrations for intraspecific dating. It is not well understood how and why the substitution rate accelerates. We have analyzed a phylogenetic tree of 3057 publicly available human mitochondrial DNA coding region sequences for changes in the ratios of mutations belonging to different functional classes. The proportion of non-synonymous and RNA genes substitutions has reduced over hundreds of thousands of years. The highest mutation ratios corresponding to fast acceleration in the apparent substitution rate of the coding sequence have occurred after the end of the Last Ice Age. We recalibrate the molecular clock of human mtDNA as 7990 years per synonymous mutation over the mitochondrial genome. However, the distribution of substitutions at synonymous sites in human data significantly departs from a model assuming a single rate parameter and implies at least 3 different subclasses of sites. Neutral model with 3 synonymous substitution rates can explain most, if not all, of the apparent molecular clock difference between the intra- and interspecies levels. Our findings imply the sluggishness of purifying selection in removing the slightly deleterious mutations from the human as well as the Neandertal and chimpanzee populations. However, for humans, the weakness of purifying selection has been further exacerbated by the population expansions associated with the out-of Africa migration and the end of the Last Ice Age.     

Molecular evolution of Pediculus humanus and the origin of clothing

The human head louse (Pediculus humanus capitis) and body louse (P. humanus corporis or P. h. humanus) are strict, obligate human ectoparasites that differ mainly in their habitat on the host : the head louse lives and feeds exclusively on the scalp, whereas the body louse feeds on the body but lives in clothing. This ecological differentiation probably arose when humans adopted frequent use of clothing, an important event in human evolution for which there is no direct archaeological evidence. We therefore used a molecular clock approach to date the origin of body lice, assuming that this should correspond with the frequent use of clothing. Sequences were obtained from two mtDNA and two nuclear DNA segments from a global sample of 40 head and body lice, and from a chimpanzee louse to use as an outgroup. The results indicate greater diversity in African than non-African lice, suggesting an African origin of human lice. A molecular clock analysis indicates that body lice originated not more than about 72,000 +/- 42,000 years ago; the mtDNA sequences also indicate a demographic expansion of body lice that correlates with the spread of modern humans out of Africa. These results suggest that clothing was a surprisingly recent innovation in human evolution.     

Deep divergences of human gene trees and models of human origins

Two competing hypotheses are at the forefront of the debate on modern human origins. In the first scenario, known as the recent Out-of-Africa hypothesis, modern humans arose in Africa about 100,000-200,000 years ago and spread throughout the world by replacing the local archaic human populations. By contrast, the second hypothesis posits substantial gene flow between archaic and emerging modern humans. In the last two decades, the young time estimates--between 100,000 and 200,000 years--of the most recent common ancestors for the mitochondrion and the Y chromosome provided evidence in favor of a recent African origin of modern humans. However, the presence of very old lineages for autosomal and X-linked genes has often been claimed to be incompatible with a simple, single origin of modern humans. Through the analysis of a public DNA sequence database, we find, similar to previous estimates, that the common ancestors of autosomal and X-linked genes are indeed very old, living, on average, respectively, 1,500,000 and 1,000,000 years ago. However, contrary to previous conclusions, we find that these deep gene genealogies are consistent with the Out-of-Africa scenario provided that the ancestral effective population size was approximately 14,000 individuals. We show that an ancient bottleneck in the Middle Pleistocene, possibly arising from an ancestral structured population, can reconcile the contradictory findings from the mitochondrion on the one hand, with the autosomes and the X chromosome on the other hand.     

DNA and recent human evolution

The study of recent human evolution, or the origin of modern humans, is currently dominated by two theories. The recent African origin hypothesis holds that there was a single origin of modern humans in Africa about 100,000 years ago, after which these humans dispersed throughout the rest of the world, mixing little or not at all with nonmodern populations. The multiregional evolution hypothesis holds that there was no single origin of modern humans but, instead, that the mutations and other traits that led to modern humans were spread in concert throughout the old world by gene flow, leading to genetic continuity among old world populations during the past million years. Although both of these theories are based on observations stemming from the fossil record, much discussion and controversy during the past six years has focused on the application and interpretation of studies of DNA variation, particularly mitochondrial DNA (mtDNA). The past year, especially, has brought new data, interpretations, and controversies. Indeed, I initially resisted writing this review, on the grounds that new information would be likely to render it obsolete by the time it was published. However, now that the dust is starting to settle, it seems timely to review various investigations and interpretations and where they are likely to lead. While the focus of this review is the mtDNA story, brief mention is made of studies of nuclear DNA variation (both autosomal and Y-chromosome DNA) and the implications of the genetic data with regard to the fossil record and our understanding of recent human evolution.     

Harvesting the fruit of the human mtDNA tree

Human mitochondrial DNA (mtDNA) studies have entered a new phase since the blossoming of complete genome analyses. Sequencing complete mtDNAs is more expensive and more labour intensive than restriction analysis or simply sequencing the control region of the molecule. But the efforts are paying off, as the phylogenetic resolution of the mtDNA tree has been greatly improved, and, in turn, phylogeographic interpretations can be given correspondingly greater precision in terms of the timing and direction of human dispersals. Therefore, despite mtDNA being only a fraction of our total genome, the deciphering of its evolution is profoundly changing our perception about how modern humans spread across our planet. Here we illustrate the phylogeographic approach with two case studies: the initial dispersal out of Africa, and the colonization of Europe.     

Time and biosequences: a contribution to the origin of modern man

The origin of modern man is still a highly debated problem. The new contributions of molecular biologists to paleontological data are numerous but discordant as these data obtained with biosequences are based on different methodologies. In order to obtain a more accurate measure of the genetic distance between extant humans and thus the deepest root of the human tree, we have reanalyzed the sequences of the regulatory region of mitochondrial DNA (D-loop) by using an improved version of the Markov Clock model devised in our laboratory. Our analysis, as well as other studies, supports the African origin of modern man. However the quantitative estimate of mtDNA evolution carried out with the corrected Markov Clock model pushes back irradiation time from Africa to 400±100 Kya. Thus according to our model there would be a genetic continuity betweenHomo erectus andHomo sapiens, who would therefore be the result of regional evolution differentiating himself under appropriate environmental pressures.     

Ancient fossil specimens of extinct species are genetically more distant to an outgroup than extant sister species are

There exists a remarkable correlation between genetic distance as measured by protein or DNA dissimilarity and time of species divergence as inferred from fossil records. This observation has provoked the molecular clock hypothesis. However, data inconsistent with the hypothesis have steadily accumulated in recent years from studies of extant organisms. Here the published DNA and protein sequences from ancient fossil specimens were examined to see if they would support the molecular clock hypothesis. The hypothesis predicts that ancient specimens cannot be genetically more distant to an outgroup than extant sister species are. Also, two distinct ancient specimens cannot be genetically more distant than their extant sister species are. The findings here do not conform to these predictions. Neanderthals are more distant to chimpanzees and gorillas than modern humans are. Dinosaurs are more distant to frogs than extant birds are. Mastodons are more distant to opossums than other placental mammals are. The genetic distance between dinosaurs and mastodons is greater than that between extant birds and mammals. Therefore, while the molecular clock hypothesis is consistent with some data from extant organisms, it has yet to find support from ancient fossils. Far more damaging to the hypothesis than data from extant organisms, which merely question the constancy of mutation rate, the study of ancient fossil organisms here challenges for the first time the fundamental premise of modern evolution theory that genetic distances had always increased with time in the past history of life on Earth.     

Dating of the human-ape splitting by a molecular clock of mitochondrial DNA

Summary A new statistical method for estimating divergence dates of species from DNA sequence data by a molecular clock approach is developed. This method takes into account effectively the information contained in a set of DNA sequence data. The molecular clock of mitochondrial DNA (mtDNA) was calibrated by setting the date of divergence between primates and ungulates at the Cretaceous-Tertiary boundary (65 million years ago), when the extinction of dinosaurs occurred. A generalized leastsquares method was applied in fitting a model to mtDNA sequence data, and the clock gave dates of 92.3±11.7, 13.3±1.5, 10.9±1.2, 3.7±0.6, and 2.7±0.6 million years ago (where the second of each pair of numbers is the standard deviation) for the separation of mouse, gibbon, orangutan, gorilla, and chimpanzee, respectively, from the line leading to humans. Although there is some uncertainty in the clock, this dating may pose a problem for the widely believed hypothesis that the bipedal creatureAustralopithecus afarensis, which lived some 3.7 million years ago at Laetoli in Tanzania and at Hadar in Ethiopia, was ancestral to man and evolved after the human-ape splitting. Another likelier possibility is that mtDNA was transferred through hybridization between a proto-human and a protochimpanzee after the former had developed bipedalism.