DNA hybridization evidence of hominoid phylogeny: Results from an expanded data set

Summary The living hominoids are human, the two species of chimpanzees, gorilla, orangutan, and nine species of gibbons. The cercopithecoids (Old World monkeys) are the sister group of the hominoids. A consensus about the phylogeny of the hominoids has been reached for the branching order of the gibbons (earliest) and the orangutan (next earliest), but the branching order among gorilla, chimpanzees, and human remains in contention. In 1984 we presented DNA-DNA hybridization data, based on 183 DNA hybrids, that we interpreted as evidence that the branching order, from oldest to most recent, was gibbons, orangutan, gorilla, chimpanzees, and human. In the present paper we report on an expanded data set totaling 514 DNA hybrids, which supports the branching order given above. The ranges for the datings of divergence nodes are Old World monkeys, 25–34 million years (Myr) ago; gibbons, 16.4–23 Myr ago; orangutan, 12.2–17 Myr ago; gorilla, 7.7–11 Myr ago; chimpanzees-human, 5.5–7.7 Myr ago. The possible effects of differences in age at first breeding are discussed, and some speculations about average genomic rates of evolution are presented.     

The gene of retroviral origin Syncytin 1 is specific to hominoids and is inactive in Old World monkeys

Syncytin 1 is one of the best known examples of recent acquisition of a new gene from an endogenous retrovirus (HERV) in the human genome and has been implicated in placental physiology. Within primates, Syncytin 1 is conserved in all hominoids but has not been characterized in Old World monkeys (OWMs). In this study, we investigated the status of Syncytin 1 in 14 hominoid and OWM species. We show that although the HERV-W provirus responsible for the origin of this gene was present in the genome of the most recent common ancestor of hominoids and OWMs, Syncytin 1 is inactive in OWMs. In addition, we were able to determine that the evolution of Syncytin 1 in hominoids involved an accumulation of amino acid changes and showed signatures of both positive and purifying selection. Our results indicate that Syncytin 1 is indeed a hominoid-specific gene and illustrate the complex and dynamic process associated with the origin of new genes.     

Structural and evolutionary analysis of an orangutan foamy virus

The full-length proviral genome of a foamy virus infecting a Bornean orangutan was amplified, and its sequence was analyzed. Although the genome showed a clear resemblance to other published foamy virus genomes from apes and monkeys, phylogenetic analysis revealed that simian foamy virus SFVora was evolutionarily equidistant from foamy viruses from other hominoids and from those from Old World monkeys. This finding suggests an independent evolution within its host over a long period of time.     

Molecular evolution of growth hormone gene family in old world monkeys and hominoids

Growth hormone is a classic molecule in the study of the molecular clock hypothesis as it exhibits a relatively constant rate of evolution in most mammalian orders except primates and artiodactyls, where dramatically enhanced rate of evolution (25–50-fold) has been reported. The rapid evolution of primate growth hormone occurred after the divergence of tarsiers and simians, but before the separation of old world monkeys (OWM) from new world monkeys (NWM). Interestingly, this event of rapid sequence evolution coincided with multiple duplications of the growth hormone gene, suggesting gene duplication as a possible cause of the accelerated sequence evolution. Here we determined 21 different GH-like sequences from four species of OWM and hominoids. Combining with published sequences from OWM and hominoids, our analysis demonstrates that multiple gene duplications and several gene conversion events both occurred in the evolutionary history of this gene family in OWM/hominoids. The episode of recent duplications of CSH-like genes in gibbon is accompanied with rapid sequence evolution likely resulting from relaxation of purifying selection. GHN genes in both hominoids and OWM are under strong purifying selection. In contrast, CSH genes in both lineages are probably not. GHV genes in OWM and hominoids evolved at different evolutionary rates and underwent different selective constraints. Our results disclosed the complex history of the primate growth hormone gene family and raised intriguing questions on the consequences of these evolutionary events.     

Evolutionary rate of immunoglobulin alpha noncoding region is greater in hominoids than in Old World monkeys.

Recent studies on the molecular evolution of primates show that the evolutionary rate among hominoids is considerably slower than that among nonhominoid primates. However, this observation at the nucleotide-sequence level is restricted to the beta-globin family region. In this study, we sequenced orthologous immunoglobulin alpha (C alpha) genes of chimpanzee, gorilla, orangutan, and crab-eating macaque (an Old World monkey) and compared them with that of the human by using noncoding regions for analysis. Since significant differences in rates among hominoids were not found by using the relative rate test, we evaluated the ratio (R) of the evolutionary distance between Old World monkey and human to the distance between orangutan and human. The R value (1.12) for the C alpha gene was much smaller than the expected value (1.38-2.33), showing that the nucleotide substitution rate (= mutation rate per year under selective neutrality) of the C alpha gene is greater in the human lineage than in the Old World monkey lineage. We also did a similar analysis for the gamma 1-, gamma 2-, psi eta-, and delta-globin genes and found a considerable heterogeneity (1.12-2.37) among the R values, including that for the C alpha gene. This indicates that the hominoid slowdown of the evolutionary rate is not a universal phenomenon in primate evolution.     

Ancestry of a human endogenous retrovirus family.

The human endogenous retrovirus type II (HERVII) family of HERV genomes has been found by Southern blot analysis to be characteristic of humans, apes, and Old World monkeys. New World monkeys and prosimians lack HERVII proviral genomes. Cellular DNAs of humans, common chimpanzees, gorillas, and orangutans, but not lesser ape lar gibbons, appear to contain the HERVII-related HLM-2 proviral genome integrated at the same site (HLM-2 maps to human chromosome 1). This suggests that the ancestral HERVII retrovirus(es) entered the genomes of Old World anthropoids by infection after the divergence of New World monkeys (platyrrhines) but before the evolutionary radiation of large hominoids.     

Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles

The variation of the Mhc-DQA1 and DQA2 loci of ten different primate species (hominoids and Old World monkeys) was studied in order to obtain an insight in the processes that generate polymorphism of major histocompatibility complex (Mhc) class II genes and to establish the evolutionary relationships of their alleles. To that end nucleotide sequences of 36 Mhc class II DQA1 and seven DQA2 second exons were determined and phylogenetic trees that illustrate their evolutionary relationships were constructed. We demonstrate the existence of four primate Mhc-DQA1 allele lineages, two of which probably existed before the separation of the ancestors of the hominoids and Old World monkeys (approximately 22–28 million years ago). Mhc-DQA2 sequences were found only in the hominoid species and showed little diversity. We found no evidence for a major contribution of recombinational events to the generation of allelic diversity of the primate Mhc-DQA1 locus. Instead, our data suggest that the primate Mhc-DQA1 and DQA2 loci are relatively stable entities that mutated primarily as a result of point mutations.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession numbers M76186-M76229.     

Molecular evolution of the psi eta-globin gene locus: gibbon phylogeny and the hominoid slowdown

An 8.4-kb genomic region spanning both the psi eta-globin gene locus and flanking DNA was sequenced from the common gibbon (Hylobates lar). In addition, sequencing of the entire orthologous region from galago (Galago crassicaudatus) was completed. The gibbon and galago sequences, along with published orthologous sequences from 10 other species, were aligned. These noncoding nucleotide sequences represented four human alleles, four apes (chimpanzee, gorilla, organgutan, and gibbon), an Old World monkey (rhesus monkey), two New World monkeys (spider and owl monkeys), tarsier, two strepsirhines (galago and lemur), and goat. Divergence and maximum parsimony analyses of the psi eta genomic region first groups humans and chimpanzees and then, at progressively more ancient branch points, successively joins gorillas, orangutans, gibbons, Old World monkeys, New World monkeys, tarsiers, and strepsirhines (the lemuriform-lorisiform branch of primates). This cladistic pattern supports the taxonomic grouping of all extant hominoids into family Hominidae, the division of Hominidae into subfamilies Hylobatinae (gibbons) and Homininae, the division of Homininae into tribes Pongini (orangutans) and Hominini, and the division of Hominini into subtribes Gorillina (gorillas) and Hominina (chimpanzees and humans). The additional gibbon and galago sequence data provide further support for the occurrence of a graded evolutionary-rate slowdown in the descent of simian primates, with the slowing rate being more pronounced in the great-ape and human lineages than in the gibbon or monkey lineages. A comparison of global versus local molecular clocks reveals that local clock predictions, when focused on a specific number of species within a narrow time frame, provide a more accurate estimate of divergence dates than do those of global clocks.     

On the loss of uricolytic activity during primate evolution--I. Silencing of urate oxidase in a hominoid ancestor

Urate oxidase activity is not detectable in liver homogenates from the gibbon, orangutan, chimpanzee, gorilla and human. Liver homogenates from five genera of Old World and two genera of New World monkeys have easily detectable levels of urate oxidase activity. There is no evidence for extant detectable intermediate steps in the loss of urate oxidase activity in the hominoids. Urate oxidase activity from Old World and New World monkeys is stable, a simple observation which debunks a long-standing myth. Urate oxidase activity was silenced in an ancestor to the five living genera of hominoids after divergence from the Old World monkeys.     

Stochastic models of molecular evolution and the estimation of phylogeny and rates of nucleotide substitution in the hominoid primates

We have estimated phylogenetic patterns and rates of nucleotide substitution in the hominoid primates using two different probabilistic models of molecular evolution as applied to three different data sets of nucleic acid sequences. The orang-utan was found to be the out-group of the other hominoids examined. Within the African apes and human clade the sister-group relationship of chimpanzee and human was found to be statistically the best, although the magnitude of the error estimates (a reflection of random statistical fluctuations) makes this conclusion tentative. The ψν-globin data sets were found to be statistically the most consistent and gave estimates of the times of divergence of chimpanzee and human from gorilla and of chimpanzee from human as 7·7 ± 1·5 Ma (Millions of years ago) and 7·4 ± 1·5 Ma respectively, although the speculative nature of these estimates is emphasized. In all cases the calibration point was the assumed divergence of the orang-utan from the remaining hominoids at 14·5 Ma. There was no statistically significant evidence of a slowdown in nucleotide substitution rate for the human lineage, or among the hominoids as a whole with respect to the Old and New World monkeys. We advocate the continued use and development of stochastic models of molecular evolution as a basis for phylogenetic estimation. On this basis one can choose between competing hypotheses of relationship in a statistical manner and can provide estimates of the errors involved in such estimations. The assumptions of all stochastic models are open to test and future refinement.     

Conformational Adaptation of Asian Macaque TRIMCyp Directs Lineage Specific Antiviral Activity

TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5α but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.     

The phylogeny of the hominoid primates,as indicated by DNA-DNA hybridization

Summary The living hominoid primates are Man, the chimpanzees, the Gorilla, the Orangutan, and the gibbons. The cercopithecoids (Old World monkeys) are the sister group of the hominoids. The composition of the Hominoidea is not in dispute, but a consensus has not yet been reached concerning the phylogenetic branching pattern and the dating of divergence nodes. We have compared the single-copy nuclear DNA sequences of the hominoid genera using DNA-DNA hybridization to produce a complete matrix of delta T₅₀H values. The data show that the branching sequence of the lineages, from oldest to most recent, was: Old World monkeys, gibbons, Orangutan, Gorilla, chimpanzees, and Man. The calibration of the delta T₅₀H scale in absolute time needs further refinement, but the ranges of our estimates of the datings of the divergence nodes are: Cercopithecoidea, 27–33 million years ago (MYA); gibbons, 18–22 MYA; Orangutan, 13–16 MYA; Gorilla, 8–10 MYA; and chimpanzees-Man, 6.3–7.7 MYA.     

Simian homologues of human herpesvirus 8

Gamma-herpesviruses can be found in most primates including Old World an New World monkeys. The gamma-herpesvirinae are grouped into two classes: lymphocryptoviruses (gamma1) and rhadinoviruses (gamma2). The lymphocryptoviruses include Epstein-Barr virus, lymphocryptovirus of rhesus monkeys, and Herpesvirus papio of baboons. Rhadinoviruses that infect New World monkeys include Herpesvirus saimiri, whose natural host is the squirrel monkey, and Herpesvirus ateles, which infects spider monkeys. Rhadinoviruses that infect hominoids and Old World monkeys include Kaposi's sarcoma-associated herpesvirus, also known as HHV-8, and rhesus monkey rhadinovirus.     

Relative rates of nuclear DNA evolution in human and Old World monkey lineages

Rates of substitution were compared between humans and Old World monkeys for sequences in or adjacent to 19 genes. The comparison of 21,299 sites in noncoding regions indicates that the substitution rate is approximately 43% greater in the Old World monkey lineage. However, 83% of the compared sites are in the region of the beta-globin gene family. Outside this region there is no consistent pattern of rate difference between the two lineages. Comparison of the coding regions of 16 genomically dispersed genes, involving 1,592 synonymous sites and 5,275 nonsynonymous sites, showed a faster rate of substitution in the human lineage at the nonsynonymous sites of the prion gene, but otherwise no evidence of rate difference between the two lineages. It is concluded that rate differences between these two lineages may be specific to certain regions of the genome rather than being a general phenomenon. This conclusion needs to be confirmed by comparison of a larger number of genomically dispersed sequences. It is, however, consistent with the results of DNA-DNA hybridization experiments, which show no difference in evolutionary rate between the two lineages.      

Formation of a new solo-LTR of the human endogenous retrovirus H family in human chromosome 21

Human endogenous retroviruses (HERVs) contribute to various kinds of genomic instability via rearrangement and retrotransposition events. In the present study the formation of a new human-specific solo-LTR belonging to the HERV-H family (AP001667; chromosome 21q21) was detected by a comparative analysis of human chromosome 21 and chimpanzee chromosome 22. The solo-LTR was formed as a result of an equal homologous recombination excision event. Several evolutionary processes have occurred at this locus during primate evolution, indicating that mammalian-wide interspersed repeat (MIR) and full-length HERV-H elements integrated into hominoid genomes after the divergence of Old World monkeys and hominoids, and that the solo-LTR element was created by recombination excision of the HERV-H only in the human genome.     

Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein

SAMHD1 has recently been identified as an HIV-1 restriction factor operating in myeloid cells. As?a countermeasure, the Vpx accessory protein from HIV-2 and certain lineages of SIV have evolved to antagonize SAMHD1 by inducing its ubiquitin-proteasome-dependent degradation. Here, we show that SAMHD1 experienced strong positive selection episodes during primate evolution that occurred in?the Catarrhini ancestral branch prior to the separation between hominoids (gibbons and great apes) and Old World monkeys. The identification of SAMHD1 residues under positive selection led to mapping the Vpx-interaction domain of SAMHD1 to its C-terminal region. Importantly, we found that while SAMHD1 restriction activity toward HIV-1 is evolutionarily maintained, antagonism of SAMHD1 by Vpx is species-specific. The distinct evolutionary signature of SAMHD1 sheds light on the development of its antiviral specificity.     

Is the Clavicle of Apes Long? An Investigation of Clavicular Length in Relation to Body Mass and Upper Thoracic Width

An elongated clavicle is one of the distinct features of apes and humans. It plays an important role in providing mobility as well as stability for the shoulder joints. The relative length of the clavicle is an especially important factor in limiting the range of shoulder joint excursion. It is said that among primates, Asian apes, i.e., gibbons and orang-utans, have very long clavicles. At the same time, they also have a wide upper thoracic cage, which may diminish the effective length of the clavicle. To clarify the length of the clavicle in apes, from the standpoint of the functional anatomy of the shoulder girdle, we examined clavicular length in 15 anthropoid species exhibiting various positional behaviors. The results confirm that clavicle length in Asian apes is long, and chimpanzees have a short clavicle like that of Old and New World monkeys, when scaled to body mass. The clavicular length of chimpanzees, however, is intermediate between Old World monkeys and Asian apes when scaled against thoracic width. Therefore, living apes can be grouped together, albeit just barely, by possession of a relatively long clavicle for their thoracic cage size. Interestingly, New World monkeys tend to exhibit a longer clavicle than Old World monkeys of equivalent body mass or thoracic cage width. Although it is unclear whether the ancestral condition of clavicular length in anthropoids was similar to that of living Old or New World monkeys, an elongation of clavicle was an important step toward evolution of the modern body plan of hominoids.     

Slow molecular clocks in Old World monkeys,apes, and humans

Two longstanding issues on the molecular clock hypothesis are studied in this article. First, is there a global molecular clock in mammals? Although many authors have observed unequal rates of nucleotide substitution among mammalian lineages, some authors have proposed a global clock for all eutherians, i.e., a single global rate of 2.2 x 10(-9) substitutions per nucleotide site per year. We reexamine this issue using noncoding, nonrepetitive DNA from Old World monkeys (OWMs), chimpanzee, and human. First, using the minimal date of 6 MYA for the human-chimpanzee divergence and more than 2.5 million base pairs of genomic sequences from human and chimpanzee, we estimate a maximal rate of 0.99 x 10(-9) for noncoding, nonrepetitive genomic regions for these two species. This estimate is less than half of the proposed global rate and much smaller than the commonly used rate (3.5 x 10(-9)) for eutherians. Further, using a minimal date of 23 MYA for the human-OWM divergence, we estimate a maximal rate of 1.5 x 10(-9) for both introns and fourfold degenerate sites in humans and OWMs. In addition, with the New World monkey (NWM) lineage as an outgroup, we estimate that the rate of substitution in introns is 30% higher in the OWM lineage than in the human lineage. Clearly, there is no global molecular clock in eutherians. Second, although many studies have indicated considerable variation in the mutation rate among regions of the mammalian genome, a recent study proposed a uniform rate. Using new and existing intron sequence data from higher primates, we find significant rate variation among genomic regions and a positive correlation between the rate of substitution and the GC content, refuting the claim of a uniform rate.     

Papio cynocephalus endogenous retrovirus among old world monkeys: evidence for coevolution and ancient cross-species transmissions

To study the evolutionary history of Papio cynocephalus endogenous retrovirus (PcEV), we analyzed the distribution and genetic characteristics of PcEV among 17 different species of primates. The viral pol-env and long terminal repeat and untranslated region (LTR-UTR) sequences could be recovered from all Old World species of the papionin tribe, which includes baboons, macaques, geladas, and mangabeys, but not from the New World monkeys and hominoids we tested. The Old World genera Cercopithecus and Miopithecus hosted either a PcEV variant with an incomplete genome or a virus with substantial mismatches in the LTR-UTR. A complete PcEV was found in the genome of Colobus guereza-but not in Colobus badius-with a copy number of 44 to 61 per diploid genome, comparable to that seen in papionins, and with a sequence most closely related to a virus of the papionin tribe. Analysis of evolutionary distances among PcEV sequences for synonymous and nonsynonymous sites indicated that purifying selection was operational during PcEV evolution. Phylogenetic analysis suggested that possibly two subtypes of PcEV entered the germ line of a common ancestor of the papionins and subsequently coevolved with their hosts. One strain of PcEV was apparently transmitted from a papionin ancestor to an ancestor of the central African lowland C. guereza.