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.     

Estimation of hominoid ancestral population sizes under bayesian coalescent models incorporating mutation rate variation and sequencing errors

Estimation of population parameters for the common ancestors of humans and the great apes is important in understanding our evolutionary history. In particular, inference of population size for the human-chimpanzee common ancestor may shed light on the process by which the 2 species separated and on whether the human population experienced a severe size reduction in its early evolutionary history. In this study, the Bayesian method of ancestral inference of Rannala and Yang (2003. Bayes estimation of species divergence times and ancestral population sizes using DNA sequences from multiple loci. Genetics. 164:1645-1656) was extended to accommodate variable mutation rates among loci and random species-specific sequencing errors. The model was applied to analyze a genome-wide data set of approximately 15,000 neutral loci (7.4 Mb) aligned for human, chimpanzee, gorilla, orangutan, and macaque. We obtained robust and precise estimates for effective population sizes along the hominoid lineage extending back approximately 30 Myr to the cercopithecoid divergence. The results showed that ancestral populations were 5-10 times larger than modern humans along the entire hominoid lineage. The estimates were robust to the priors used and to model assumptions about recombination. The unusually low X chromosome divergence between human and chimpanzee could not be explained by variation in the male mutation bias or by current models of hybridization and introgression. Instead, our parameter estimates were consistent with a simple instantaneous process for human-chimpanzee speciation but showed a major reduction in X chromosome effective population size peculiar to the human-chimpanzee common ancestor, possibly due to selective sweeps on the X prior to separation of the 2 species.     

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.     

Estimating ancestral population sizes and divergence times

This article presents a new method for jointly estimating species divergence times and ancestral population sizes. The method improves on previous ones by explicitly incorporating intragenic recombination, by utilizing orthologous sequence data from closely related species, and by using a maximum-likelihood framework. The latter allows for efficient use of the available information and provides a way of assessing how much confidence we should place in the estimates. I apply the method to recently collected intergenic sequence data from humans and the great apes. The results suggest that the human-chimpanzee ancestral population size was four to seven times larger than the current human effective population size and that the current human effective population size is slightly >10,000. These estimates are similar to previous ones, and they appear relatively insensitive to assumptions about the recombination rates or mutation rates across loci.     

Nucleotide diversity in gorillas

Comparison of the levels of nucleotide diversity in humans and apes may provide valuable information for inferring the demographic history of these species, the effect of social structure on genetic diversity, patterns of past migration, and signatures of past selection events. Previous DNA sequence data from both the mitochondrial and the nuclear genomes suggested a much higher level of nucleotide diversity in the African apes than in humans. Noting that the nuclear DNA data from the apes were very limited, we previously conducted a DNA polymorphism study in humans and another in chimpanzees and bonobos, using 50 DNA segments randomly chosen from the noncoding, nonrepetitive parts of the human genome. The data revealed that the nucleotide diversity (pi) in bonobos (0.077%) is actually lower than that in humans (0.087%) and that pi in chimpanzees (0.134%) is only 50% higher than that in humans. In the present study we sequenced the same 50 segments in 15 western lowland gorillas and estimated pi to be 0.158%. This is the highest value among the African apes but is only about two times higher than that in humans. Interestingly, available mtDNA sequence data also suggest a twofold higher nucleotide diversity in gorillas than in humans, but suggest a threefold higher nucleotide diversity in chimpanzees than in humans. The higher mtDNA diversity in chimpanzees might be due to the unique pattern in the evolution of chimpanzee mtDNA. From the nuclear DNA pi values, we estimated that the long-term effective population sizes of humans, bonobos, chimpanzees, and gorillas are, respectively, 10,400, 12,300, 21,300, and 25,200.     

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]     

Bayes estimation of species divergence times and ancestral population sizes using DNA sequences from multiple loci

The effective population sizes of ancestral as well as modern species are important parameters in models of population genetics and human evolution. The commonly used method for estimating ancestral population sizes, based on counting mismatches between the species tree and the inferred gene trees, is highly biased as it ignores uncertainties in gene tree reconstruction. In this article, we develop a Bayes method for simultaneous estimation of the species divergence times and current and ancestral population sizes. The method uses DNA sequence data from multiple loci and extracts information about conflicts among gene tree topologies and coalescent times to estimate ancestral population sizes. The topology of the species tree is assumed known. A Markov chain Monte Carlo algorithm is implemented to integrate over uncertain gene trees and branch lengths (or coalescence times) at each locus as well as species divergence times. The method can handle any species tree and allows different numbers of sequences at different loci. We apply the method to published noncoding DNA sequences from the human and the great apes. There are strong correlations between posterior estimates of speciation times and ancestral population sizes. With the use of an informative prior for the human-chimpanzee divergence date, the population size of the common ancestor of the two species is estimated to be approximately 20,000, with a 95% credibility interval (8000, 40,000). Our estimates, however, are affected by model assumptions as well as data quality. We suggest that reliable estimates have yet to await more data and more realistic models.     

Speciational history of Australian grass finches (Poephila) inferred from thirty gene trees

Multilocus genealogical approaches are still uncommon in phylogeography and historical demography, fields which have been dominated by microsatellite markers and mitochondrial DNA, particularly for vertebrates. Using 30 newly developed anonymous nuclear loci, we estimated population divergence times and ancestral population sizes of three closely related species of Australian grass finches (Poephila) distributed across two barriers in northern Australia. We verified that substitution rates were generally constant both among lineages and among loci, and that intralocus recombination was uncommon in our dataset, thereby satisfying two assumptions of our multilocus analysis. The reconstructed gene trees exhibited all three possible tree topologies and displayed considerable variation in coalescent times, yet this information provided the raw data for maximum likelihood and Bayesian estimation of population divergence times and ancestral population sizes. Estimates of these parameters were in close agreement with each other regardless of statistical approach and our Bayesian estimates were robust to prior assumptions. Our results suggest that black-throated finches (Poephila cincta) diverged from long-tailed finches (P. acuticauda and P. hecki) across the Carpentarian Barrier in northeastern Australia around 0.6 million years ago (mya), and that P. acuticauda diverged from P. hecki across the Kimberley Plateau-Arnhem Land Barrier in northwestern Australia approximately 0.3 mya. Bayesian 95% credibility intervals around these estimates strongly support Pleistocene timing for both speciation events, despite the fact that many gene divergences across the Carpentarian region clearly predated the Pleistocene. Estimates of ancestral effective population sizes for the basal ancestor and long-tailed finch ancestor were large (about 521,000 and about 384,000, respectively). Although the errors around the population size parameter estimates are considerable, they are the first for birds taking into account multiple sources of variance.     

Strong Selective Sweeps on the X Chromosome in the Human-Chimpanzee Ancestor Explain Its Low Divergence

The human and chimpanzee X chromosomes are less divergent than expected based on autosomal divergence. We study incomplete lineage sorting patterns between humans, chimpanzees and gorillas to show that this low divergence can be entirely explained by megabase-sized regions comprising one-third of the X chromosome, where polymorphism in the human-chimpanzee ancestral species was severely reduced. We show that background selection can explain at most 10% of this reduction of diversity in the ancestor. Instead, we show that several strong selective sweeps in the ancestral species can explain it. We also report evidence of population specific sweeps in extant humans that overlap the regions of low diversity in the ancestral species. These regions further correspond to chromosomal sections shown to be devoid of Neanderthal introgression into modern humans. This suggests that the same X-linked regions that undergo selective sweeps are among the first to form reproductive barriers between diverging species. We hypothesize that meiotic drive is the underlying mechanism causing these two observations.     

Natural selection on the olfactory receptor gene family in humans and chimpanzees

The olfactory receptor (OR) genes constitute the largest gene family in mammalian genomes. Humans have >1,000 OR genes, of which only ~40% have an intact coding region and are therefore putatively functional. In contrast, the fraction of intact OR genes in the genomes of the great apes is significantly greater (68%–72%), suggesting that selective pressures on the OR repertoire vary among these species. We have examined the evolutionary forces that shaped the OR gene family in humans and chimpanzees by resequencing 20 OR genes in 16 humans, 16 chimpanzees, and one orangutan. We compared the variation at the OR genes with that at intergenic regions. In both humans and chimpanzees, OR pseudogenes seem to evolve neutrally. In chimpanzees, patterns of variability are consistent with purifying selection acting on intact OR genes, whereas, in humans, there is suggestive evidence for positive selection acting on intact OR genes. These observations are likely due to differences in lifestyle, between humans and great apes, that have led to distinct sensory needs.     

Molecular Views of Human Origins

Over the last half century, comparative genomics has increasingly contributed to the definition, resolution and interpretation of human evolution. Early comparisons demonstrated that African apes and humans were more closely related and diverged later than commonly thought. However, it was difficult to determine the branching between humans, chimpanzees and gorillas. By the 1990s, sufficient biomolecular data had accumulated to demonstrate that chimpanzees and humans shared a common ancestor after the divergence of the gorilla. Current reconstructions place the divergence of humans and chimpanzees at 6–8 million years. Comparative genomics from complete genome sequencing to chromosome painting provide a scenario for the origin of the human genome. Starting form the ancestral mammalian karyotype, we can determine the major steps over the last 90 million years leading to the formation of each human chromosome. Despite considerable technical problems, studies of ancient DNA now provide a direct genetic witness of human evolution and add a temporal dimension to reconstructions of our evolutionary history and phylogeny. Ancient DNA has shown that Neanderthals probably did not interbreed with anatomically modern humans and did not make a significant contribution to the gene pool of our species. Ancient DNA has also contributed to the studies of the colonization of the Americas and the Pacific Island, and the domestication of plants and animals. Understanding the genetic basis of the physical and behavioral traits that distinguish humans from other primates presents one of the great future challenges of science.     

Molecular diversity of entodiniomorphid ciliate Troglodytella abrassarti and its coevolution with chimpanzees

The entodiniomorphid ciliate Troglodytella abrassarti is a colonic mutualist of great apes. Its host specificity makes it a suitable model for studies of primate evolution. We explored molecular diversity of T. abrassarti with regard to large geographical distribution and taxonomic diversity of its most common host, the chimpanzee. We found a very low diversification of T. abrassarti in chimpanzees across Africa. Distribution of two types of T. abrassarti supports evolutionary separation of the Western chimpanzee, P. t. verus, from populations in Central and East Africa. Type I T. abrassarti is probably a derived form, which corresponds with the Central African origin of chimpanzees and a founder event leading to P. t. verus. Exclusivity of the respective types of T. abrassarti to Western and Central/Eastern chimpanzees corroborates the difference found between an introduced population of presumed Western chimpanzees on Rubondo Island and an autochthonous population in mainland Tanzania. The identity of T. abrassarti from Nigerian P. t. ellioti and Central African chimpanzees suggests their close evolutionary relationship. Although this contrasts with published mtDNA data, it corroborates current opinion on the exclusive position of P. t. verus within the chimpanzee phylogeny. The type of T. abrassarti occurring in Central and East African common chimpanzee was confirmed also in bonobos. This may point to the presence of an ancestral Type II found throughout the Lower Guinean rainforest dating back to the common Pan ancestor. Alternatively, the molecular uniformity of T. abrassarti may imply a historical overlap of the species' distribution ranges.     

Spinopelvic pathways to bipedality: why no hominids ever relied on a bent-hip–bent-knee gait

Until recently, the last common ancestor of African apes and humans was presumed to resemble living chimpanzees and bonobos. This was frequently extended to their locomotor pattern leading to the presumption that knuckle-walking was a likely ancestral pattern, requiring bipedality to have emerged as a modification of their bent-hip-bent-knee gait used during erect walking. Research on the development and anatomy of the vertebral column, coupled with new revelations from the fossil record (in particular, Ardipithecus ramidus), now demonstrate that these presumptions have been in error. Reassessment of the potential pathway to early hominid bipedality now reveals an entirely novel sequence of likely morphological events leading to the emergence of upright walking.     

African ape ancestry

It is commonly believed that the australopithecines are more closely related to humans than to African apes. This view is hardly compatible with the biomolecular data which place theHomo/Pan split at the beginning of the australopithecine period. Nothing in the fossil hominid morphology precludes the possibility that some australopithecines were ancestral to gorillas or chimpanzees and others to humans.     

A simple method of removing the effect of a bottleneck and unequal population sizes on pairwise genetic distances

In this paper, we derive the expectation of two popular genetic distances under a model of pure population fission allowing for unequal population sizes. Under the model, we show that conventional genetic distances are not proportional to the divergence time and generally overestimate it due to unequal genetic drift and to a bottleneck effect at the divergence time. This bias cannot be totally removed even if the present population sizes are known. Instead, we present a method to estimate the divergence times between populations which is based on the average number of nucleotide differences within and between populations. The method simultaneously estimates the divergence time, the ancestral population size and the relative sizes of the derived populations. A simulation study revealed that this method is essentially unbiased and that it leads to better estimates than traditional approaches for a very wide range of parameter values. Simulations also indicated that moderate population growth after divergence has little effect on the estimates of all three estimated parameters. An application of our method to a comparison of humans and chimpanzee mitochondrial DNA diversity revealed that common chimpanzees have a significantly larger female population size than humans.     

A brief history of human autosomes.

Comparative gene mapping and chromosome painting permit the tentative reconstruction of ancestral karyotypes. The modern human karyotype is proposed to differ from that of the most recent common ancestor of catarrhine primates by two major rearrangements. The first was the fission of an ancestral chromosome to produce the homologues of human chromosomes 14 and 15. This fission occurred before the divergence of gibbons from humans and other apes. The second was the fusion of two ancestral chromosomes to form human chromosome 2. This fusion occurred after the divergence of humans and chimpanzees. Moving further back in time, homologues of human chromosomes 3 and 21 were formed by the fission of an ancestral linkage group that combined loci of both human chromosomes, whereas homologues of human chromosomes 12 and 22 were formed by a reciprocal translocation between two ancestral chromosomes. Both events occurred at some time after our most recent common ancestor with lemurs. Less direct evidence suggests that the short and long arms of human chromosomes 8, 16 and 19 were unlinked in this ancestor. Finally, the most recent common ancestor of primates and artiodactyls is proposed to have possessed a chromosome that combined loci from human chromosomes 4 and 8p, a chromosome that combined loci from human chromosomes 16q and 19q, and a chromosome that combined loci from human chromosomes 2p and 20.     

Evolution of a HOXB6 intergenic region within the great apes and humans

Data accumulated over the past decade from several loci suggest that nonhuman primates have a greater amount of intraspecific genetic variation relative to humans. In phylogenetic reconstructions among primates that are based on genetic data, therefore, it becomes essential to adequately sample the population(s) being analyzed. Inadequate sampling may not only underestimate variation within any given population, but such an underestimate may confound any phylogenetic or population-specific conclusions implied by the data. Here we present inter- and intraspecific data on the molecular evolution of an approximately 1.0 kb intergenic HOXB6 sequence among humans, common chimpanzees, pygmy chimpanzees, gorillas and orangutans. To date, this study represents the most comprehensive investigation of a noncoding nuclear locus among the great apes and humans that examines the nature and amount of intraspecific variation in DNA sequences. Not only do these HOXB6 data continue to support earlier findings that Homo sapiens sapiens has less genetic variation than any great ape species (Ruano et al., 1992; Deinard & Kidd, 1995), but they strongly suggest that a high level of genetic polymorphism existed within the common ancestor of the African ape clade (Homo-Pan-Gorilla). Despite detecting two nucleotide substitutions linking Pan and Homo, we caution against concluding that the HOXB6 data definitively support a Homo-Pan clade to the exclusion of Gorilla. Rather, we believe that taking into consideration the level of genetic polymorphism that is likely to have existed within the common ancestor, the most prudent conclusion that can be made from all available data, including morphological, karyotypic and genetic data, may be that speciation among Homo-Pan-Gorilla is best represented by a "trichotomy".     

Molecular trajectories leading to the alternative fates of duplicate genes

Gene duplication generates extra gene copies in which mutations can accumulate without risking the function of pre-existing genes. Such mutations modify duplicates and contribute to evolutionary novelties. However, the vast majority of duplicates appear to be short-lived and experience duplicate silencing within a few million years. Little is known about the molecular mechanisms leading to these alternative fates. Here we delineate differing molecular trajectories of a relatively recent duplication event between humans and chimpanzees by investigating molecular properties of a single duplicate: DNA sequences, gene expression and promoter activities. The inverted duplication of the Glutathione S-transferase Theta 2 (GSTT2) gene had occurred at least 7 million years ago in the common ancestor of African great apes and is preserved in chimpanzees (Pan troglodytes), whereas a deletion polymorphism is prevalent in humans. The alternative fates are associated with expression divergence between these species, and reduced expression in humans is regulated by silencing mutations that have been propagated between duplicates by gene conversion. In contrast, selective constraint preserved duplicate divergence in chimpanzees. The difference in evolutionary processes left a unique DNA footprint in which dying duplicates are significantly more similar to each other (99.4%) than preserved ones. Such molecular trajectories could provide insights for the mechanisms underlying duplicate life and death in extant genomes.     

The evolution of hominoid cranial diversity: A quantitative genetic approach

Hominoid cranial evolution is characterized by substantial phenotypic diversity, yet the cause of this variability has rarely been explored. Quantitative genetic techniques for investigating evolutionary processes underlying morphological divergence are dependent on the availability of good ancestral models, a problem in hominoids where the fossil record is fragmentary and poorly understood. Here, we use a maximum likelihood approach based on a Brownian motion model of evolutionary change to estimate nested hypothetical ancestral forms from 15 extant hominoid taxa. These ancestors were then used to calculate rates of evolution along each branch of a phylogenetic tree using Lande's generalized genetic distance. Our results show that hominoid cranial evolution is characterized by strong stabilizing selection. Only two instances of directional selection were detected; the divergence of Homo from its last common ancestor with Pan, and the divergence of the lesser apes from their last common ancestor with the great apes. In these two cases, selection gradients reconstructed to identify the specific traits undergoing selection indicated that selection on basicranial flexion, cranial vault expansion, and facial retraction characterizes the divergence of Homo, whereas the divergence of the lesser apes was defined by selection on neurocranial size reduction.     

Evolution of the second orangutan: phylogeny and biogeography of hominid origins

Aim To resolve the phylogeny of humans and their fossil relatives (collectively, hominids), orangutans (Pongo) and various Miocene great apes and to present a biogeographical model for their differentiation in space and time. Location Africa, northern Mediterranean, Asia. Methods Maximum parsimony analysis was used to assess phylogenetic relationships among living large‐bodied hominoids (= humans, chimpanzees, bonobos, gorillas, orangutans), and various related African, Asian and European ape fossils. Biogeographical characteristics were analysed for vicariant replacement, main massings and nodes. A geomorphological correlation was identified for a clade we refer to as the ‘dental hominoids’, and this correlation was used to reconstruct their historical geography. Results Our analyses support the following hypotheses: (1) the living large‐bodied hominoids represent a monophyletic group comprising two sister clades: humans + orangutans, and chimpanzees (including bonobos) + gorillas (collectively, the African apes); and (2) the human–orangutan clade (dental hominoids) includes fossil hominids (Homo, australopiths, Orrorin) and the Miocene‐age apes Hispanopithecus, Ouranopithecus, Ankarapithecus, Sivapithecus, Lufengpithecus, Khoratpithecus and Gigantopithecus (also Plio‐Pleistocene of eastern Asia). We also demonstrate that the distributions of living and fossil genera are largely vicariant, with nodes of geographical overlap or proximity between Gigantopithecus and Sivapithecus in Central Asia, and between Pongo, Gigantopithecus, Lufengpithecus and Khoratpithecus in East Asia. The main massing is represented by five genera and eight species in East Asia. The dental hominoid track is spatially correlated with the East African Rift System (EARS) and the Tethys Orogenic Collage (TOC). Main conclusions Humans and orangutans share a common ancestor that excludes the extant African apes. Molecular analyses are compromised by phenetic procedures such as alignment and are probably based on primitive retentions. We infer that the human–orangutan common ancestor had established a widespread distribution by at least 13 Ma. Vicariant differentiation resulted in the ancestors of hominids in East Africa and various primarily Miocene apes distributed between Spain and Southeast Asia (and possibly also parts of East Africa). The geographical disjunction between early hominids and Asian Pongo is attributed to local extinctions between Europe and Central Asia. The EARS and TOC correlations suggest that these geomorphological features mediated establishment of the ancestral range.