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.     

The nonidentity of invariable positions in the cytochromes c of different species

This study answers the question: Are the variable and invariable codons of cytochrome c largely the same in all species? A method is presented for estimating the number of invariable (as opposed to unvaried) codons common to two taxa. The two taxa in this study were comprised of four fungi and four metazoans. Given the number of mutations fixed in each taxon, one calculates the number of codons that would be expected to have fixed mutations in both taxa, in one taxon only, in the other taxon only, and in neither taxon. This expectation depends upon the number of invariable codons that are assumed to be common to both taxa. In the present example, the assumption of 41 invariable codons in common leads to estimates that deviate by less than 2% from the values actually observed. This leads to the conclusion that there are 46 positions that are variable in one taxon but invariable in the other, thereby demonstrating that the invariable codons are not largely the same between the fungi and the metazoans.     

Mitochondrial DNA evolution in lagomorphs: Origin of systematic heteroplasmy and organization of diversity in European rabbits

Summary A characterization was conducted on mitochondrial DNA (mtDNA) molecules extracted separately from 107 European rabbits (Oryctolagus cuniculus) both wild and domestic, 13 European hares (Lepus capensis), and 1 eastern cottontail (Sylvilagus floridanus). Experimentally this study took into account restriction site polymorphism, overall length variation of the noncoding region, and numbers of repeated sequences. Nucleotide divergences indicate that the mtDNAs from the three species derived from a common ancestor some 6–8 million years (Myr) ago. Every animal appeared heteroplasmic for a set of molecules with various lengths of the noncoding region and variable numbers of repeated sequences that contribute to them. This systematic heteroplasmy, most probably generated by a rate of localized mtDNA rearrangements high enough to counterbalance the cellular segregation of rearranged molecules, is a shared derived character of leporids.The geographic distribution of mtDNA polymorphism among wild rabbit populations over the western European basin shows that two molecular lineages are represented, one in southern Spain, the second over northern Spain, France, and Tunisia. These two lineages derived from a common ancestor some 2 Myr ago. Their present geographical distribution may be correlated to the separation of rabbits into two stocks at the time of Mindel glaciation.Finally the distribution of mtDNA diversity exhibits a mosaic pattern both at inter- and intrapopulation levels.     

Modern African ape populations as genetic and demographic models of the last common ancestor of humans, chimpanzees, and gorillas

In order to fully understand human evolutionary history through the use of molecular data, it is essential to include our closest relatives as a comparison. We provide here estimates of nucleotide diversity and effective population size of modern African ape species using data from several independent noncoding nuclear loci, and use these estimates to make predictions about the nature of the ancestral population that eventually gave rise to the living species of African apes, including humans. Chimpanzees, bonobos, and gorillas possess two to three times more nucleotide diversity than modern humans. We hypothesize that the last common ancestor (LCA) of these species had an effective population size more similar to modern apes than modern humans. In addition, estimated dates for the divergence of the Homo, Pan, and Gorilla lineages suggest that the LCA may have had stronger geographic structuring to its mtDNA than its nuclear DNA, perhaps indicative of strong female philopatry or a dispersal system analogous to gorillas, where females disperse only short distances from their natal group. Synthesizing different classes of data, and the inferences drawn from them, allows us to predict some of the genetic and demographic properties of the LCA of humans, chimpanzees, and gorillas.     

New approaches to dating suggest a recent age for the human mtDNA ancestor.

The most critical and controversial feature of the African origin hypothesis of human mitochondrial DNA (mtDNA) evolution is the relatively recent age of about 200 ka inferred for the human mtDNA ancestor. If this age is wrong, and the actual age instead approaches 1 million years ago, then the controversy abates. Reliable estimates of the age of the human mtDNA ancestor and the associated standard error are therefore crucial. However, more recent estimates of the age of the human ancestor rely on comparisons between human and chimpanzee mtDNAs that may not be reliable and for which standard errors are difficult to calculate. We present here two approaches for deriving an intraspecific calibration of the rate of human mtDNA sequence evolution that allow standard errors to be readily calculated. The estimates resulting from these two approaches for the age of the human mtDNA ancestor (and approximate 95% confidence intervals) are 133 (63-356) and 137 (63-416) ka ago. These results provide the strongest evidence yet for a relatively recent origin of the human mtDNA ancestor.     

Indonesian mitochondrial DNA and its opposition to a Pleistocene era origin of proto-Polynesians in island southeast Asia

The origin of modern Polynesians, the route of their expansion into the Pacific Ocean, and the timing of their movements all remain contentious topics in modern anthropology. Numerous studies have used molecular data to elucidate settlement patterns in the Indo-Pacific region, but the same evidence is often interpreted in opposing ways by different researchers. Above all, mitochondrial DNA (mtDNA) diversity has been used to discriminate between competing migration models and has narrowed the probable source of proto-Polynesian peoples to southern China and Taiwan or eastern Indonesia. Richards et al. (1998) used a dating method employing the p statistic to argue for an origin of Polynesian peoples in eastern Indonesia during the Pleistocene (> 10,000 years ago). Here, the time to the most recent common ancestor (TMRCA) is recalculated for a new series of Indonesian mtDNA sequences with Polynesian affinities. These data, which incorporate additional sequences published after 1998, produce dates that cannot rule out the possibility of a common ancestor for these sequences during the Holocene (< 10,000 years ago). This implies that previous estimates of TMRCA dates for Indonesian sequences lacked the statistical robustness necessary for replicability. The extant mtDNA evidence can no longer be viewed as favoring a Polynesian origin in eastern Indonesia, but instead remains consistent with an origin of proto-Polynesian peoples in southern China and Taiwan.     

Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees

To study the genomic divergences among hominoids and to estimate the effective population size of the common ancestor of humans and chimpanzees, we selected 53 autosomal intergenic nonrepetitive DNA segments from the human genome and sequenced them in a human, a chimpanzee, a gorilla, and an orangutan. The average sequence divergence was only 1.24% +/- 0.07% for the human-chimpanzee pair, 1.62% +/- 0.08% for the human-gorilla pair, and 1.63% +/- 0.08% for the chimpanzee-gorilla pair. These estimates, which were confirmed by additional data from GenBank, are substantially lower than previous ones, which included repetitive sequences and might have been based on less-accurate sequence data. The average sequence divergences between orangutans and humans, chimpanzees, and gorillas were 3.08% +/- 0.11%, 3.12% +/- 0.11%, and 3.09% +/- 0.11%, respectively, which also are substantially lower than previous estimates. The sequence divergences in other regions between hominoids were estimated from extensive data in GenBank and the literature, and Alus showed the highest divergence, followed in order by Y-linked noncoding regions, pseudogenes, autosomal intergenic regions, X-linked noncoding regions, synonymous sites, introns, and nonsynonymous sites. The neighbor-joining tree derived from the concatenated sequence of the 53 segments--24,234 bp in length--supports the Homo-Pan clade with a 100% bootstrap value. However, when each segment is analyzed separately, 22 of the 53 segments (approximately 42%) give a tree that is incongruent with the species tree, suggesting a large effective population size (N(e)) of the common ancestor of Homo and Pan. Indeed, a parsimony analysis of the 53 segments and 37 protein-coding genes leads to an estimate of N(e) = 52,000 to 96,000. As this estimate is 5 to 9 times larger than the long-term effective population size of humans (approximately 10,000) estimated from various genetic polymorphism data, the human lineage apparently had experienced a large reduction in effective population size after its separation from the chimpanzee lineage. Our analysis assumes a molecular clock, which is in fact supported by the sequence data used. Taking the orangutan speciation date as 12 to 16 million years ago, we obtain an estimate of 4.6 to 6.2 million years for the Homo-Pan divergence and an estimate of 6.2 to 8.4 million years for the gorilla speciation date, suggesting that the gorilla lineage branched off 1.6 to 2.2 million years earlier than did the human-chimpanzee divergence.     

Genome digging: insight into the mitochondrial genome of Homo

Background

A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt) on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1) into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split.

Principal Findings

Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2) with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000–485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively.

Conclusions

This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The d_N/d_S dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective population size and possessed genetic diversity comparable with those of chimpanzee and gorilla.     

Estimating the number of ancestral lineages using a maximum-likelihood method based on rejection sampling

Estimating the number of ancestral lineages of a sample of DNA sequences at time t in the past can be viewed as a variation on the problem of estimating the time to the most recent common ancestor. To estimate the number of ancestral lineages, we develop a maximum-likelihood approach that takes advantage of a prior model of population demography, in addition to the molecular data summarized by the pattern of polymorphic sites. The method relies on a rejection sampling algorithm that is introduced for simulating conditional coalescent trees given a fixed number of ancestral lineages at time t. Computer simulations show that the number of ancestral lineages can be estimated accurately, provided that the number of mutations that occurred since time t is sufficiently large. The method is applied to 986 present-day human sequences located in hypervariable region 1 of the mitochondrion to estimate the number of ancestral lineages of modern humans at the time of potential admixture with the Neanderthal population. Our estimates support a view that the proportion of the modern population consisting of Neanderthal contributions must be relatively small, less than approximately 5%, if the admixture happened as recently as 30,000 years ago.     

Neanderthals

Neanderthals are a group of fossil humans that inhabited Western Eurasia from approximately 300 to 30,000 years ago (ka). They vanished from the fossil record a few millennia after the first modern humans appeared in Europe (ca. 40 ka BP). They are characterized by a unique combination of distinctive anatomical features, and are found with stone tools of the Mousterian stone tool industry. Current consensus views them as a distinct Eurasian human lineage isolated from the rest of the Old World and sharing a common ancestor with modern humans sometime in the early Middle Pleistocene. The extreme cold of the European Ice Ages is considered at least partly responsible for the evolution of some of the distinctive Neanderthal anatomy, although other factors (functional demands, effects of chance in small populations) were probably also important. The causes for the Neanderthal extinction are not well understood. Worsening climate and competition with modern humans are implicated. Neanderthals were our sister species, much more closely related to us than the chimpanzees, our closest living relatives are today.     

Nucleotide variation and haplotype diversity in a 10-kb noncoding region in three continental human populations

Noncoding regions are usually less subject to natural selection than coding regions and so may be more useful for studying human evolution. The recent surveys of worldwide DNA variation in four 10-kb noncoding regions revealed many interesting but also some incongruent patterns. Here we studied another 10-kb noncoding region, which is in 6p22. Sixty-six single-nucleotide polymorphisms were found among the 122 worldwide human sequences, resulting in 46 genotypes, from which 48 haplotypes were inferred. The distribution patterns of DNA variation, genotypes, and haplotypes suggest rapid population expansion in relatively recent times. The levels of polymorphism within human populations and divergence between humans and chimpanzees at this locus were generally similar to those for the other four noncoding regions. Fu and Li's tests rejected the neutrality assumption in the total sample and in the African sample but Tajima's test did not reject neutrality. A detailed examination of the contributions of various types of mutations to the parameters used in the neutrality tests clarified the discrepancy between these test results. The age estimates suggest a relatively young history in this region. Combining three autosomal noncoding regions, we estimated the long-term effective population size of humans to be 11,000 ± 2800 using Tajima's estimator and 17,600 ± 4700 using Watterson's estimator and the age of the most recent common ancestor to be 860,000 ± 258,000 years ago.     

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.     

DNA polymorphism in a worldwide sample of human X chromosomes

DNA sequence data from humans can provide insight into the history of modern humans and the genetic variability in human populations. We report here a study of human DNA sequence variation at an X-linked noncoding region of 10,346 bp. The sample consists of 62 X chromosomes from Africa, Europe, and Asia. Forty-four polymorphic sites were found among the 62 sequences, resulting in 23 different haplotypes. Statistical analyses of the data led to the following inferences. (1) There is strong evidence of human population expansion in the relatively recent past, and this population expansion has had a significant effect on the pattern of polymorphism at this locus. (2) Non-African populations were unlikely to have been derived from a very small number of African lineages. (3) There was considerable geographic subdivision in the ancient human population, which could be an important reason why many studies failed to detect population expansion. (4) The long-term effective population size of humans is between 12,000 and 15,000. And (5) a non-African specific variant was found at a frequency of 35% in non-Africans, an estimate supported by the genotyping of additional 80 non-African and 106 African X chromosomes. This variant could have arisen in Eurasia more than 140,000 years ago, predating the emergence of modern humans. Moreover, this haplotype and all other haplotypes coalesced to the most recent common ancestor of the sample, which was estimated to be older than 490,000 years. Therefore, this region may have a long history in Eurasia.     

Man's place in hominoidea revealed by mitochondrial DNA genealogy

Summary Molecular biology has resurrected C. Darwin and T.H. Huxley's question about the origin of humans, but the precise branching pattern and dating remain controversial. To settle this issue, a large amount of sequence information is required. We determined mitochondrial (mt) DNA sequences for five hominoids; pygmy and common chimpanzees, gorilla, orangutan, and siamang. The common region compared with the known human sequence is 4759 by long, encompassing genes for 11 transfer RNAs and 6 proteins. Because of the high substitution rates in mammalian mtDNA and an unprecedentedly large region compared, the sequence differences clearly indicate that the closest relatives to human are chimpanzees rather than gorilla. For dating the divergences of human, chimpanzee, and gorilla, we used only unsaturated parts of sequence differences in which the mtDNA genealogy is not obscured by multiple substitutions. The result suggests that gorilla branched off 7.7 ± 0.7 million years (Myr) ago and human 4.7 ± 0.5 Myr ago; the time difference between these divergences being as long as 3 Myr.Offprint requests to: S. Horai     

Likelihood and Bayes estimation of ancestral population sizes in hominoids using data from multiple loci

Polymorphisms in an ancestral population can cause conflicts between gene trees and the species tree. Such conflicts can be used to estimate ancestral population sizes when data from multiple loci are available. In this article I extend previous work for estimating ancestral population sizes to analyze sequence data from three species under a finite-site nucleotide substitution model. Both maximum-likelihood (ML) and Bayes methods are implemented for joint estimation of the two speciation dates and the two population size parameters. Both methods account for uncertainties in the gene tree due to few informative sites at each locus and make an efficient use of information in the data. The Bayes algorithm using Markov chain Monte Carlo (MCMC) enjoys a computational advantage over ML and also provides a framework for incorporating prior information about the parameters. The methods are applied to a data set of 53 nuclear noncoding contigs from human, chimpanzee, and gorilla published by Chen and Li. Estimates of the effective population size for the common ancestor of humans and chimpanzees by both ML and Bayes methods are approximately 12,000-21,000, comparable to estimates for modern humans, and do not support the notion of a dramatic size reduction in early human populations. Estimates published previously from the same data are several times larger and appear to be biased due to methodological deficiency. The divergence between humans and chimpanzees is dated at approximately 5.2 million years ago and the gorilla divergence 1.1-1.7 million years earlier. The analysis suggests that typical data sets contain useful information about the ancestral population sizes and that it is advantageous to analyze data of several species simultaneously.     

Genetic evidence for unequal effective population sizes of human females and males

The time to the most recent common ancestor (TMRCA) of the human mitochondria (mtDNA) is estimated to be older than that of the nonrecombining portion of the Y chromosome (NRY). Surveys of variation in globally distributed humans typically result in mtDNA TMRCA values just under 200 thousand years ago (kya), whereas those for the NRY range between 46 and 110 kya. A favored hypothesis for this finding is that natural selection has acted on the NRY, leading to a recent selective sweep. An alternate hypothesis is that sex-biased demographic processes are responsible. Here, we re-examine the disparity between NRY and mtDNA TMRCAs using data collected from individual human populations--a sampling strategy that minimizes the confounding influence of population subdivision in global data sets. We survey variation at 782 bp of the mitochondrial cytochrome c oxidase subunit 3 gene as well as at 26.5 kb of noncoding DNA from the NRY in a sample of 25 Khoisan, 24 Mongolians, and 24 Papua New Guineans. Data from both loci in all populations are best described by a model of constant population size, with the exception of Mongolian mtDNA, which appears to be experiencing rapid population growth. Taking these demographic models into account, we estimate the TMRCAs for each locus in each population. A pattern that is remarkably consistent across all three populations is an approximately twofold deeper coalescence for mtDNA than for the NRY. The oldest TMRCAs are observed for the Khoisan (73.6 kya for the NRY and 176.5 kya for mtDNA), whereas those in the non-African populations are consistently lower (averaging 47.7 kya for the NRY and 92.8 kya for mtDNA). Our data do not suggest that differential natural selection is the cause of this difference in TMRCAs. Rather, these results are most consistent with a higher female effective population size.     

An African American Paternal Lineage Adds an Extremely Ancient Root to the Human Y Chromosome Phylogenetic Tree

We report the discovery of an African American Y chromosome that carries the ancestral state of all SNPs that defined the basal portion of the Y chromosome phylogenetic tree. We sequenced ∼240 kb of this chromosome to identify private, derived mutations on this lineage, which we named A00. We then estimated the time to the most recent common ancestor (TMRCA) for the Y tree as 338 thousand years ago (kya) (95% confidence interval = 237–581 kya). Remarkably, this exceeds current estimates of the mtDNA TMRCA, as well as those of the age of the oldest anatomically modern human fossils. The extremely ancient age combined with the rarity of the A00 lineage, which we also find at very low frequency in central Africa, point to the importance of considering more complex models for the origin of Y chromosome diversity. These models include ancient population structure and the possibility of archaic introgression of Y chromosomes into anatomically modern humans. The A00 lineage was discovered in a large database of consumer samples of African Americans and has not been identified in traditional hunter-gatherer populations from sub-Saharan Africa. This underscores how the stochastic nature of the genealogical process can affect inference from a single locus and warrants caution during the interpretation of the geographic location of divergent branches of the Y chromosome phylogenetic tree for the elucidation of human origins.     

The derived FOXP2 variant of modern humans was shared with Neandertals

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.     

Os fossiles humains des grottes Muierii et Cioclovina, Roumanie

This paper presents the cultural and archaeological context of the human fossil bones from Muierii Cave, dated by us to the age of 30 150 ± 800 ¹⁴C years BP (Before Present) or 34 810 ± 927 cal years BP (calibrated years Before Present), and from Cioclovina Cave, dated to the age of 29 000 ± 700 ¹⁴C years BP or 33 540 ± 832 cal years BP, in the Southern Carpathians. These are among the most ancient dated human fossil remains from Central and South-Eastern Europe and are described in conjunction with other sites with Mousterian assemblages of the recent Neanderthal population, and sites with Aurignacian assemblage of early modern humans, from Romanian region, for the interval of time 34,000-26,000, the transitional period from the Middle Paleolithic to the Upper Paleolithic.     

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。