Mitochondrial population genomics supports a single pre-Clovis origin with a coastal route for the peopling of the Americas

It is well accepted that the Americas were the last continents reached by modern humans, most likely through Beringia. However, the precise time and mode of the colonization of the New World remain hotly disputed issues. Native American populations exhibit almost exclusively five mitochondrial DNA (mtDNA) haplogroups (A-D and X). Haplogroups A-D are also frequent in Asia, suggesting a northeastern Asian origin of these lineages. However, the differential pattern of distribution and frequency of haplogroup X led some to suggest that it may represent an independent migration to the Americas. Here we show, by using 86 complete mitochondrial genomes, that all Native American haplogroups, including haplogroup X, were part of a single founding population, thereby refuting multiple-migration models. A detailed demographic history of the mtDNA sequences estimated with a Bayesian coalescent method indicates a complex model for the peopling of the Americas, in which the initial differentiation from Asian populations ended with a moderate bottleneck in Beringia during the last glacial maximum (LGM), around approximately 23,000 to approximately 19,000 years ago. Toward the end of the LGM, a strong population expansion started approximately 18,000 and finished approximately 15,000 years ago. These results support a pre-Clovis occupation of the New World, suggesting a rapid settlement of the continent along a Pacific coastal route.     

Archaic African and Asian lineages in the genetic ancestry of modern humans.

A 3-kb region encompassing the beta-globin gene has been analyzed for allelic sequence polymorphism in nine populations from Africa, Asia, and Europe. A unique gene tree was constructed from 326 sequences of 349 in the total sample. New maximum-likelihood methods for analyzing gene trees on the basis of coalescence theory have been used. The most recent common ancestor of the beta-globin gene tree is a sequence found only in Africa and estimated to have arisen approximately 800,000 years ago. There is no evidence for an exponential expansion out of a bottlenecked founding population, and an effective population size of approximately 10,000 has been maintained. Modest differences in levels of beta-globin diversity between Africa and Asia are better explained by greater African effective population size than by greater time depth. There may have been a reduction of Asian effective population size in recent evolutionary history. Characteristically Asian ancestry is estimated to be older than 200,000 years, suggesting that the ancestral hominid population at this time was widely dispersed across Africa and Asia. Patterns of beta-globin diversity suggest extensive worldwide late Pleistocene gene flow and are not easily reconciled with a unidirectional migration out of Africa 100,000 years ago and total replacement of archaic populations in Asia.     

Inferring human population sizes, divergence times and rates of gene flow from mitochondrial, X and Y chromosome resequencing data

We estimate parameters of a general isolation-with-migration model using resequence data from mitochondrial DNA (mtDNA), the Y chromosome, and two loci on the X chromosome in samples of 25-50 individuals from each of 10 human populations. Application of a coalescent-based Markov chain Monte Carlo technique allows simultaneous inference of divergence times, rates of gene flow, as well as changes in effective population size. Results from comparisons between sub-Saharan African and Eurasian populations estimate that 1500 individuals founded the ancestral Eurasian population approximately 40 thousand years ago (KYA). Furthermore, these small Eurasian founding populations appear to have grown much more dramatically than either African or Oceanian populations. Analyses of sub-Saharan African populations provide little evidence for a history of population bottlenecks and suggest that they began diverging from one another upward of 50 KYA. We surmise that ancestral African populations had already been geographically structured prior to the founding of ancestral Eurasian populations. African populations are shown to experience low levels of mitochondrial DNA gene flow, but high levels of Y chromosome gene flow. In particular, Y chromosome gene flow appears to be asymmetric, i.e., from the Bantu-speaking population into other African populations. Conversely, mitochondrial gene flow is more extensive between non-African populations, but appears to be absent between European and Asian populations.     

Craniometric variation and the settlement of the Americas: testing hypotheses by means of R-matrix and matrix correlation analyses

New archaeological findings and the incorporation of new South American skull samples have raised fundamental questions for the classical theories of the Americas' settlement. The aim of this study was to estimate craniometric variability among several Asian and Native American populations in order to test goodness of fit of the data to different models of ancient population entries and dispersions into the New World. Our data set includes Howells' variables recorded on East Asian, North American, and South American natives (except for Na-Dene speakers). Five Fuego-Patagonian samples and one Paleoamerican sample were also included. A multivariate extension of the R-matrix method for quantitative traits was used to obtain Fst values, which were considered estimations of intergroup variation. Three main models for the peopling of the New World were represented in hypothetical design matrices. Matrix permutation tests were performed to quantify the fit of the observed data with 1) geographical separation of the samples and 2) three ways of settlement, which were the Three Migration Model (TMM), the Single Wave Migration model (SWM), and the Two Components Settlement Model (TCS). R-matrix results showed high levels of heterogeneity among Native Americans. Matrix permutation analyses suggested that the model involving high Amerindian heterogeneity and two different morphological patterns or components (derived "Mongoloid" vs. generalized "non-Mongoloid") explains better the variation observed, even when the effects of geographical separation are removed. Whether these patterns arose as a result of two separate migration events or by local evolution from Paleoamericans to Amerindians remains unresolved.     

Did pre-Columbian populations of the Amazonian biome reach carrying capacity during the Late Holocene?

The increasingly better-known archaeological record of the Amazon basin, the Orinoco basin and the Guianas both questions the long-standing premise of a pristine tropical rainforest environment and also provides evidence for major biome-scale cultural and technological transitions prior to European colonization. Associated changes in pre-Columbian human population size and density, however, are poorly known and often estimated on the basis of unreliable assumptions and guesswork. Drawing on recent developments in the aggregate analysis of large radiocarbon databases, here we present and examine different proxies for relative population change between 1050 BC and AD 1500 within this broad region. By using a robust model testing approach, our analyses document that the growth of pre-Columbian human population over the 1700 years prior to European colonization adheres to a logistic model of demographic growth. This suggests that, at an aggregate level, these pre-Columbian populations had potentially reached carrying capacity (however high) before the onset of European colonization. Our analyses also demonstrate that this aggregate scenario shows considerable variability when projected geographically, highlighting significant gaps in archaeological knowledge yet also providing important insights into the resilience of past human food procurement strategies. By offering a new understanding of biome-wide pre-Columbian demographic trends based on empirical evidence, our analysis hopes to unfetter novel perspectives on demic expansions, language diversification trajectories and subsistence intensification processes in the Amazonian biome during the late Holocene.This article is part of the theme issue ‘Cross-disciplinary approaches to prehistoric demography’.     

Peopling of the Americas: paleobiological evidence.

A subjective and bivariate analysis of 8500-10,000-year-old human fossil remains from North America substantiates that the fossils' closest affinities are with Asian populations. Within North American prehistoric Indian populations, increasing brachycephalization and the possible development of a larger, broader face are two structural trends that can be identified. In those respects where Paleo-Indian specimens differ from modern northern Asians and North American Indians, they tend to resemble southern Asian and European populations. These assessments generally support the inference that populations entered the New World relatively recently but before the modern northern Asian and North American features were fully developed. Based on the data examined, no date can be specified for time of entrance of the first populations, nor can the number of founding populations be discerned.     

A geographically explicit genetic model of worldwide human-settlement history

Currently available genetic and archaeological evidence is generally interpreted as supportive of a recent single origin of modern humans in East Africa. However, this is where the near consensus on human settlement history ends, and considerable uncertainty clouds any more detailed aspect of human colonization history. Here, we present a dynamic genetic model of human settlement history coupled with explicit geographical distances from East Africa, the likely origin of modern humans. We search for the best-supported parameter space by fitting our analytical prediction to genetic data that are based on 52 human populations analyzed at 783 autosomal microsatellite markers. This framework allows us to jointly estimate the key parameters of the expansion of modern humans. Our best estimates suggest an initial expansion of modern humans approximately 56,000 years ago from a small founding population of approximately 1,000 effective individuals. Our model further points to high growth rates in newly colonized habitats. The general fit of the model with the data is excellent. This suggests that coupling analytical genetic models with explicit demography and geography provides a powerful tool for making inferences on human-settlement history.     

Examination of the relationship between inbreeding and population size

This chapter presents a method for examining the relationship between effective population size and accumulated random inbreeding in human populations. Using a linear regression model on 9 Irish isolates, results show that this method is very useful in assessing differential influences on population structure. Inbreeding refers to the level expected at random due to finite population size, offset by migration into the population. The data used consist of effective population size estimates and kinship estimates derived from surnames for 9 isolates on, or near, the west coast of Ireland. Based on the non-parametric correlation results, there is no monotonic relationship between effective population size and the inverse of kinship. The demographic data available show that, with the exception of Garumna, Lettermullen, and the Aran Islands, the other populations changed little in population size during the latter part of the 19th century. The fact that observed kinship is higher than predicted kinship suggests an increse in population size. These analyses suggest that there is little, if any, relationship between population size and inbreeding among these populations, using 1891 effective population size estimates. Given the range of demogrphic, ecological, and cultural environments of human populations, perhaps it is unexpected to see a set of populations adhering strongly to a given theoretical model. The more important aspect of such model fitting is not whether or not a given model shows a significant fit, but rather the analysis of deviations from an expected relationship.     

Allelic genealogy and human evolution

Genetic variation at most loci examined in human populations indicates that the (effective) population size has been approximately 10(4) for the past 1 Myr and that individuals have been genetically united rather tightly. Also suggested is that the population size has never dropped to a few individuals, even in a single generation. These impose important requirements for the hypotheses for the origin of modern humans: a relatively large population size and frequent migration if populations were geographically subdivided. Any hypothesis that assumes a small number of founding individuals throughout the late Pleistocene can be rejected. Extraordinary polymorphism at some loci of the major histocompatibility complex (Mhc) rules out the past action of severe bottlenecks, or the so-called founder principle, which invokes only a small number of founding individuals when a new species emerges. This conclusion may be extended to the 35-Myr-old history of the human lineage, because some polymorphism at Mhc loci seems to have lasted that long. Furthermore, although the population structure prior to the late Pleistocene is less clear, owing to the insensitivity of Mhc alleles, even to low levels of migration, the nature of Mhc polymorphism suggests that the effective size of populations leading to humans was as large as 10(5). Hence, the effective population size of humans might have become somewhat smaller in most of the late Pleistocene. The reduction could be due either to the then adverse environment in the Old World and/or to the increased migration rate. It is also argued that population explosion fostered by the agriculture revolution has had significant effects on incorporating new alleles into human populations.      

The South African australopithecines: A palaeodemographic analysis

Anthropologists, demographers and historians alike are continually seeking information about demographic profiles of prehistoric and ancient human populations. There are many different approaches relevant to the problem, yet direct evidence of the demographic structure of any archaeological population is primarily provided by analysis of human skeletal and dental remains. This offers a possibility of extending demographic inferences back to Pliocene — Early Pleistocene times, which, in turn, would enhance our understanding of the principles of human survival, adaptation, social interaction and demographic evolution of man. Data on the age distribution of South African australopithecines has been analysed using life-table analysis, based on a stationary population model. The estimated demographic profile is the evaluated and interpreted within a framework of biological, cultural and ecological circumstances. It is concluded that palaeodemography, if carefully undertaken, can play a real and pragmatic role in understanding the demographic history of man.     

Population growth of human Y chromosomes: a study of Y chromosome microsatellites

We use variation at a set of eight human Y chromosome microsatellite loci to investigate the demographic history of the Y chromosome. Instead of assuming a population of constant size, as in most of the previous work on the Y chromosome, we consider a model which permits a period of recent population growth. We show that for most of the populations in our sample this model fits the data far better than a model with no growth. We estimate the demographic parameters of this model for each population and also the time to the most recent common ancestor. Since there is some uncertainty about the details of the microsatellite mutation process, we consider several plausible mutation schemes and estimate the variance in mutation size simultaneously with the demographic parameters of interest. Our finding of a recent common ancestor (probably in the last 120,000 years), coupled with a strong signal of demographic expansion in all populations, suggests either a recent human expansion from a small ancestral population, or natural selection acting on the Y chromosome.     

On the importance of being structured: instantaneous coalescence rates and human evolution—lessons for ancestral population size inference?

Most species are structured and influenced by processes that either increased or reduced gene flow between populations. However, most population genetic inference methods assume panmixia and reconstruct a history characterized by population size changes. This is potentially problematic as population structure can generate spurious signals of population size change through time. Moreover, when the model assumed for demographic inference is misspecified, genomic data will likely increase the precision of misleading if not meaningless parameters. For instance, if data were generated under an n-island model (characterized by the number of islands and migrants exchanged) inference based on a model of population size change would produce precise estimates of a bottleneck that would be meaningless. In addition, archaeological or climatic events around the bottleneck''s timing might provide a reasonable but potentially misleading scenario. In a context of model uncertainty (panmixia versus structure) genomic data may thus not necessarily lead to improved statistical inference. We consider two haploid genomes and develop a theory that explains why any demographic model with structure will necessarily be interpreted as a series of changes in population size by inference methods ignoring structure. We formalize a parameter, the inverse instantaneous coalescence rate, and show that it is equivalent to a population size only in panmictic models, and is mostly misleading for structured models. We argue that this issue affects all population genetics methods ignoring population structure which may thus infer population size changes that never took place. We apply our approach to human genomic data.     

MHC variability supports dog domestication from a large number of wolves: high diversity in Asia

The process of dog domestication is still somewhat unresolved. Earlier studies indicate that domestic dogs from all over the world have a common origin in Asia. So far, major histocompatibility complex (MHC) diversity has not been studied in detail in Asian dogs, although high levels of genetic diversity are expected at the domestication locality. We sequenced the second exon of the canine MHC gene DLA–DRB1 from 128 Asian dogs and compared our data with a previously published large data set of MHC alleles, mostly from European dogs. Our results show that Asian dogs have a higher MHC diversity than European dogs. We also estimated that there is only a small probability that new alleles have arisen by mutation since domestication. Based on the assumption that all of the currently known 102 DLA–DRB1 alleles come from the founding wolf population, we simulated the number of founding wolf individuals. Our simulations indicate an effective population size of at least 500 founding wolves, suggesting that the founding wolf population was large or that backcrossing has taken place.     

mtDNA history of the Cayapa Amerinds of Ecuador: detection of additional founding lineages for the Native American populations.

mtDNA variation in the Cayapa, an Ecuadorian Amerindian tribe belonging to the Chibcha-Paezan linguistic branch, was analyzed by use of hypervariable control regions I and II along with two linked regions undergoing insertion/deletion mutations. Three major maternal lineage clusters fit into the A, B, and C founding groups first described by Schurr and colleagues in 1990, whereas a fourth lineage, apparently unique to the Cayapa, has ambiguous affinity to known clusters. The time of divergence from a common maternal ancestor of the four lineage groups is of sufficient age that it indicates an origin in Asia and supports the hypothesis that the degree of variability carried by the Asian ancestral populations into the New World was rather high. Spatial autocorrelation analysis points out (a) statistically significant nonrandom distributions of the founding lineages in the Americas, because of north-south population movements that have occurred since the first Asian migrants spread through Beringia into the Americas, and (b) an unusual pattern associated with the D lineage cluster. The values of haplotype and nucleotide diversity that are displayed by the Cayapa appear to differ from those observed in other Chibchan populations but match those calculated for South American groups belonging to various linguistic stocks. These data, together with the results of phylogenetic analysis performed with the Amerinds of Central and South America, highlight the difficulty in the identification of clear coevolutionary patterns between linguistic and genetic relationships in particular human populations.     

Inferring the Demographic History of African Farmers and Pygmy Hunter–Gatherers Using a Multilocus Resequencing Data Set

The transition from hunting and gathering to farming involved a major cultural innovation that has spread rapidly over most of the globe in the last ten millennia. In sub-Saharan Africa, hunter–gatherers have begun to shift toward an agriculture-based lifestyle over the last 5,000 years. Only a few populations still base their mode of subsistence on hunting and gathering. The Pygmies are considered to be the largest group of mobile hunter–gatherers of Africa. They dwell in equatorial rainforests and are characterized by their short mean stature. However, little is known about the chronology of the demographic events—size changes, population splits, and gene flow—ultimately giving rise to contemporary Pygmy (Western and Eastern) groups and neighboring agricultural populations. We studied the branching history of Pygmy hunter–gatherers and agricultural populations from Africa and estimated separation times and gene flow between these populations. We resequenced 24 independent noncoding regions across the genome, corresponding to a total of ~33 kb per individual, in 236 samples from seven Pygmy and five agricultural populations dispersed over the African continent. We used simulation-based inference to identify the historical model best fitting our data. The model identified included the early divergence of the ancestors of Pygmy hunter–gatherers and farming populations ~60,000 years ago, followed by a split of the Pygmies' ancestors into the Western and Eastern Pygmy groups ~20,000 years ago. Our findings increase knowledge of the history of the peopling of the African continent in a region lacking archaeological data. An appreciation of the demographic and adaptive history of African populations with different modes of subsistence should improve our understanding of the influence of human lifestyles on genome diversity.     

Local extinction and recolonization, species effective population size, and modern human origins

A primary objection from a population genetics perspective to a multiregional model of modern human origins is that the model posits a large census size, whereas genetic data suggest a small effective population size. The relationship between census size and effective size is complex, but arguments based on an island model of migration show that if the effective population size reflects the number of breeding individuals and the effects of population subdivision, then an effective population size of 10,000 is inconsistent with the census size of 500,000 to 1,000,000 that has been suggested by archeological evidence. However, these models have ignored the effects of population extinction and recolonization, which increase the expected variance among demes and reduce the inbreeding effective population size. Using models developed for population extinction and recolonization, we show that a large census size consistent with the multiregional model can be reconciled with an effective population size of 10,000, but genetic variation among demes must be high, reflecting low interdeme migration rates and a colonization process that involves a small number of colonists or kin-structured colonization. Ethnographic and archeological evidence is insufficient to determine whether such demographic conditions existed among Pleistocene human populations, and further work needs to be done. More realistic models that incorporate isolation by distance and heterogeneity in extinction rates and effective deme sizes also need to be developed. However, if true, a process of population extinction and recolonization has interesting implications for human demographic history.     

Migration patterns among global populations of the pathogenic fungus Mycosphaerella graminicola

DNA sequences from five nuclear loci and data from three microsatellites were collected from 360 isolates representing 14 globally distributed populations of the plant pathogenic fungus Mycosphaerella graminicola. Haplotype networks were constructed for the five sequence loci and population subdivision was assessed using Hudson's permutation test. Migration estimates were calculated using six regional populations for both the sequence and microsatellite loci. While subdivision was detected among the six regional populations, significant gene flow was indicated among some of the populations. The European and Israeli populations contributed the majority of historical immigrants to the New World. Migration estimates for microsatellite loci were used to infer more recent migration events among specific New World populations. We conclude that gene flow was an important factor in determining the demographic history of Mycosphaerella graminicola.     

Ancestral Population Sizes and Species Divergence Times in the Primate Lineage on the Basis of Intron and BAC End Sequences

The effective sizes of ancestral populations and species divergence times of six primate species (humans, chimpanzees, gorillas, orangutans, and representatives of Old World monkeys and New World monkeys) are estimated by applying the two-species maximum likelihood (ML) method to intron sequences of 20 different loci. Examination of rate heterogeneity of nucleotide substitutions and intragenic recombination identifies five outrageous loci (ODC1, GHR, HBE, INS, and HBG). The estimated ancestral polymorphism ranges from 0.21 to 0.96% at major divergences in primate evolution. One exceptionally low polymorphism occurs when African and Asian apes diverged. However, taking into consideration the possible short generation times in primate ancestors, it is concluded that the ancestral population size in the primate lineage was no smaller than that of extant humans. Furthermore, under the assumption of 6 million years (myr) divergence between humans and chimpanzees, the divergence time of humans from gorillas, orangutans, Old World monkeys, and New World monkeys is estimated as 7.2, 18, 34, and 65 myr ago, respectively, which are generally older than traditional estimates. Beside the intron sequences, three other data sets of orthologous sequences are used between the human and the chimpanzee comparison. The ML application to these data sets including 58,156 random BAC end sequences (BES) shows that the nucleotide substitution rate is as low as 0.6–0.8 × 10^–9 per site per year and the extent of ancestral polymorphism is 0.33–0.51%. With such a low substitution rate and short generation time, the relatively high extent of polymorphism suggests a fairly large effective population size in the ancestral lineage common to humans and chimpanzees.[Reviewing Editor: Dr. Magnus Nordborg]     

Demographic history of a common pioneer tree,Zanthoxylum ailanthoides,reconstructed using isolation-with-migration model

The Japanese prickly ash, Zanthoxylum ailanthoides Siebold & Zucc. (Rutaceae), is one of the most common pioneer tree species that grow in disturbed areas, such as canopy gaps, in Japanese warm-temperate evergreen oak forests. The strong genetic structure of its current population might suggest long-term isolation of subpopulations by demographic events, in addition to ecological features of this species. Analyses of genome-wide nucleotide variation using model-based approaches are necessary to achieve a good understanding of the demographic history of a species. In this study, we analyzed the nucleotide variation in natural populations of Z. ailanthoides using a computer program that applied the isolation-with-migration model to quantitatively infer the demographic history. Nucleotide variations at 10 or 26 nuclear loci in six populations from a wide range of the species distribution were analyzed. The maximum likelihood estimate of the divergence time between the current populations in the two hypothetical refugia of Z. ailanthoides was approximately 24,000 years. Unexpectedly, the estimated size of the ancestral population was larger than the sizes of the two current populations. The results suggested a relatively recent divergence of these two populations and rapid formation of strong genetic structure among subpopulations. The large ancestral population may indicate a more complex demographic history during or after the last glacial period than the simple isolation-with-migration model implies.