Elevated diversity in loci linked to facial morphology is consistent with the hypothesis that individual facial recognition is important across hominoids.

OBJECTIVES: The ability to use visual signals to identify individuals is an important feature of primate social groups, including humans. Sheehan and Nachman (2014) showed that loci linked to facial morphology had elevated levels of diversity and interpreted this as evidence that the human face is under frequency-dependent selection to enhance individual recognition (Nature Communications 5). In our study, we tested whether this pattern is found in non-human ape species, to help understand whether individual recognition might also play a role in species other than humans. MATERIALS AND METHODS: We examined levels of genetic diversity in an available population genomic dataset of humans, chimpanzees, bonobos, gorillas, and orangutans for three sets of loci, (1) loci linked to facial morphology, (2) loci linked to height, and (3) neutrally evolving regions. We tested whether loci linked to facial morphology were more variable than loci linked to height or neutrally evolving loci in each of these species. RESULTS: We found significantly elevated diversity in loci linked to facial morphology in chimpanzees, gorillas, and Sumatran and Bornean orangutans. DISCUSSION: Our findings closely parallel those of Sheehan and Nachman and are consistent with the idea that selection for facial diversity and individual recognition has not only shaped the evolution of the human face, but it has similarly shaped the evolution of most of our closest primate relatives. We also discuss alternative hypotheses for this pattern.

Hominoid intraspecific cranial variation mirrors neutral genetic diversity.

Natural selection, developmental constraint, and plasticity have all been invoked as explanations for intraspecific cranial variation in humans and apes. However, global patterns of human cranial variation are congruent with patterns of genetic variation, demonstrating that population history has influenced cranial variation in humans. Here we show that this finding is not unique to Homo sapiens but is also broadly evident across extant ape species. Specifically, taxa that exhibit greater intraspecific cranial shape variation also exhibit greater genetic diversity at neutral autosomal loci. Thus, cranial shape variation within hominoid taxa reflects the population history of each species. Our results suggest that neutral evolutionary processes such as mutation, gene flow, and genetic drift have played an important role in generating cranial variation within species. These findings are consistent with previous work on human cranial morphology and improve our understanding of the evolutionary processes that generate intraspecific cranial shape diversity within hominoids. This work has implications for the analysis of selective and developmental pressures on the cranium and for interpreting shape variation in fossil hominin crania.

Elite swimmers do not exhibit a body mass index trade-off across a wide range of event distances.

There is a trade-off reflected in the contrasting phenotypes of elite long-distance runners, who are typically leaner, and elite sprinters, who are usually more heavily muscled. It is unclear, however, whether and how swimmers' bodies vary across event distances from the 50 m swim, which is about a 20-30 s event, to the 10 000 m marathon swim, which is about a 2 h event. We examined data from the 2012 Olympics to test whether swimmers' phenotypes differed across event distances. We show that across all swimming event distances, from the 50 m sprint to the 10 000 m marathon, swimmers converge on a single optimal body mass index (BMI) in men's and women's events, in marked contrast with the strong inverse relationship between BMI and event distance found in runners. The absence of a speed-endurance trade-off in the body proportions of swimmers indicates a fundamental difference in design pressures and performance capability in terrestrial versus aquatic environments.

Strong links between genomic and anatomical diversity in both mammalian olfactory chemosensory systems.

Mammalian olfaction comprises two chemosensory systems: the odorant-detecting main olfactory system (MOS) and the pheromone-detecting vomeronasal system (VNS). Mammals are diverse in their anatomical and genomic emphases on olfactory chemosensation, including the loss or reduction of these systems in some orders. Despite qualitative evidence linking the genomic evolution of the olfactory systems to specific functions and phenotypes, little work has quantitatively tested whether the genomic aspects of the mammalian olfactory chemosensory systems are correlated to anatomical diversity. We show that the genomic and anatomical variation in these systems is tightly linked in both the VNS and the MOS, though the signature of selection is different in each system. Specifically, the MOS appears to vary based on absolute organ and gene family size while the VNS appears to vary according to the relative proportion of functional genes and relative anatomical size and complexity. Furthermore, there is little evidence that these two systems are evolving in a linked fashion. The relationships between genomic and anatomical diversity strongly support a role for natural selection in shaping both the anatomical and genomic evolution of the olfactory chemosensory systems in mammals.

Molecular phylogenetic analysis of the Papionina using concatenation and species tree methods.

The Papionina is a geographically widespread subtribe of African cercopithecid monkeys whose evolutionary history is of particular interest to anthropologists. The phylogenetic relationships among arboreal mangabeys (Lophocebus), baboons (Papio), and geladas (Theropithecus) remain unresolved. Molecular phylogenetic analyses have revealed marked gene tree incongruence for these taxa, and several recent concatenated phylogenetic analyses of multilocus datasets have supported different phylogenetic hypotheses. To address this issue, we investigated the phylogeny of the Lophocebus + Papio + Theropithecus group using concatenation methods, as well as alternative methods that incorporate gene tree heterogeneity to estimate a 'species tree.' Our compiled DNA sequence dataset was ∼56 kb pairs long and included 57 independent partitions. All analyses of concatenated alignments strongly supported a Lophocebus + Papio clade and a basal position for Theropithecus. The Bayesian concordance analysis supported the same phylogeny. A coalescent-based Bayesian method resulted in a very poorly resolved species tree. The topological agreement between concatenation and the Bayesian concordance analysis offers considerable support for a Lophocebus + Papio clade as the dominant relationship across the genome. However, the results of the Bayesian concordance analysis indicate that almost half the genome has an alternative history. As such, our results offer a well-supported phylogenetic hypothesis for the Papio/Lophocebus/Theropithecus trichotomy, while at the same time providing evidence for a complex evolutionary history that likely includes hybridization among lineages.

Evidence for a convergent slowdown in primate molecular rates and its implications for the timing of early primate evolution.

A long-standing problem in primate evolution is the discord between paleontological and molecular clock estimates for the time of crown primate origins: the earliest crown primate fossils are ~56 million y (Ma) old, whereas molecular estimates for the haplorhine-strepsirrhine split are often deep in the Late Cretaceous. One explanation for this phenomenon is that crown primates existed in the Cretaceous but that their fossil remains have not yet been found. Here we provide strong evidence that this discordance is better-explained by a convergent molecular rate slowdown in early primate evolution. We show that molecular rates in primates are strongly and inversely related to three life-history correlates: body size (BS), absolute endocranial volume (EV), and relative endocranial volume (REV). Critically, these traits can be reconstructed from fossils, allowing molecular rates to be predicted for extinct primates. To this end, we modeled the evolutionary history of BS, EV, and REV using data from both extinct and extant primates. We show that the primate last common ancestor had a very small BS, EV, and REV. There has been a subsequent convergent increase in BS, EV, and REV, indicating that there has also been a convergent molecular rate slowdown over primate evolution. We generated a unique timescale for primates by predicting molecular rates from the reconstructed phenotypic values for a large phylogeny of living and extinct primates. This analysis suggests that crown primates originated close to the K-Pg boundary and possibly in the Paleocene, largely reconciling the molecular and fossil timescales of primate evolution.

The SLC4A1 gene is under differential selective pressure in primates infected by Plasmodium falciparum and related parasites.

Malaria is a disease caused by Plasmodium parasites and is responsible for high mortality in humans. This disease is caused by four different species of Plasmodium though the main source of mortality is Plasmodium falciparum. Humans have a number of genetic adaptations that act to combat Plasmodium. One adaptation is a deletion in the SLC4A1 gene that leads to Southeast Asian ovalocytosis (SAO). There is evidence that SAO erythrocytes are resistant to multiple Plasmodium species. Here we analyze SLC4A1 in 23 primates and mammals to test for differential selective pressures among different primate lineages. Because primates are infected with both human Plasmodium parasites and their relatives, this analysis can be used to test which human Plasmodium parasite is the likely target of SAO. A significantly different pattern of molecular evolution was found in humans and African apes, species that are infected by P. falciparum and its relatives. This effect was restricted to the cytosolic domain of the SLC4A1 gene. The evidence is consistent with a different selective regime operating on this gene domain in humans and African apes, when compared to other primates and mammals. Alternatively, this pattern is consistent with a relaxation of selection or weak adaptive evolution operating on a small number of amino acids. The adaptive interpretation of the results is consistent with the SAO allele of the SLC4A1 gene interacting with P. falciparum in humans, rather than other Plasmodium parasites. However, additional investigation of the relationship between SLC4A1 variants and Plasmodium in humans and African apes is required to test whether the different selective regime in humans and African apes is due to natural selection or relaxed constraint.

Genomic data reject the hypothesis of a prosimian primate clade.

The phylogenetic position of tarsiers within the primates has been a controversial subject for over a century. Despite numerous morphological and molecular studies, there has been weak support for grouping tarsiers with either strepsirrhine primates in a prosimian clade or with anthropoids in a haplorrhine clade. Here, we take advantage of the recently released whole genome assembly of the Philippine tarsier, Tarsius syrichta, in order to infer the phylogenetic relationship of Tarsius within the order Primates. We also present estimates of divergence times within the primates. Using a 1.26 million base pair multiple sequence alignment derived from 1078 orthologous genes, we provide overwhelming statistical support for the presence of a haplorrhine clade. We also present divergence date estimates using local relaxed molecular clock methods. The estimated time of the most recent common ancestor of extant Primates ranged from 64.9 Ma to 72.6 Ma, and haplorrhines were estimated to have a most recent common ancestor between 58.9 Ma and 68.6 Ma. Examination of rates of nucleotide substitution in the three major extant primate clades show that anthropoids have a slower substitution rate than either strepsirrhines or tarsiers. Our results provide the framework on which primate morphological, reproductive, and genomic features can be reconstructed in the broader context of mammalian phylogeny.

Dating primate divergences through an integrated analysis of palaeontological and molecular data.

Estimation of divergence times is usually done using either the fossil record or sequence data from modern species. We provide an integrated analysis of palaeontological and molecular data to give estimates of primate divergence times that utilize both sources of information. The number of preserved primate species discovered in the fossil record, along with their geological age distribution, is combined with the number of extant primate species to provide initial estimates of the primate and anthropoid divergence times. This is done by using a stochastic forwards-modeling approach where speciation and fossil preservation and discovery are simulated forward in time. We use the posterior distribution from the fossil analysis as a prior distribution on node ages in a molecular analysis. Sequence data from two genomic regions (CFTR on human chromosome 7 and the CYP7A1 region on chromosome 8) from 15 primate species are used with the birth-death model implemented in mcmctree in PAML to infer the posterior distribution of the ages of 14 nodes in the primate tree. We find that these age estimates are older than previously reported dates for all but one of these nodes. To perform the inference, a new approximate Bayesian computation (ABC) algorithm is introduced, where the structure of the model can be exploited in an ABC-within-Gibbs algorithm to provide a more efficient analysis.

Fossil and molecular evidence constrain scenarios for the early evolutionary and biogeographic history of hystricognathous rodents.

The early evolutionary and paleobiogeographic history of the diverse rodent clade Hystricognathi, which contains Hystricidae (Old World porcupines), Caviomorpha (the endemic South American rodents), and African Phiomorpha (cane rats, dassie rats, and blesmols) is of great interest to students of mammalian evolution, but remains poorly understood because of a poor early fossil record. Here we describe the oldest well-dated hystricognathous rodents from an earliest late Eocene (approximately 37 Ma) fossil locality in the Fayum Depression of northern Egypt. These taxa exhibit a combination of primitive and derived features, the former shared with Asian "baluchimyine" rodents, and the latter shared with Oligocene phiomorphs and caviomorphs. Phylogenetic analysis incorporating morphological, temporal, geographic, and molecular information places the new taxa as successive sister groups of crown Hystricognathi, and supports an Asian origin for stem Hystricognathi and an Afro-Arabian origin for crown Hystricognathi, stem Hystricidae, and stem Caviomorpha. Molecular dating of early divergences within Hystricognathi, using a Bayesian "relaxed clock" approach and multiple fossil calibrations, suggests that the split between Hystricidae and the phiomorph-caviomorph clade occurred approximately 39 Ma, and that phiomorphs and caviomorphs diverged approximately 36 Ma. These results are remarkably congruent with our phylogenetic results and the fossil record of hystricognathous rodent evolution in Afro-Arabia and South America.

Mitochondrial COII Introgression into the Nuclear Genome of Gorilla gorilla.

Numts are nonfunctional mitochondrial sequences that have translocated into nuclear DNA, where they evolve independently from the original mitochondrial DNA (mtDNA) sequence. Numts can be unintentionally amplified in addition to authentic mtDNA, complicating both the analysis and interpretation of mtDNA-based studies. Amplification of numts creates particular issues for studies on the noncoding, hypervariable 1 mtDNA region of gorillas. We provide data on putative numt sequences of the coding mitochondrial gene cytochrome oxidase subunit II (COII). Via polymerase chain reaction (PCR) and cloning, we obtained COII sequences for gorilla, orangutan, and human high-quality DNA and also from a gorilla fecal DNA sample. Both gorilla and orangutan samples yielded putative numt sequences. Phylogenetically more anciently transferred numts were amplified with a greater incidence from the gorilla fecal DNA sample than from the high-quality gorilla sample. Data on phylogenetically more recently transferred numts are equivocal. We further demonstrate the need for additional investigations into the use of mtDNA markers for noninvasively collected samples from gorillas and other primates.

Phylogenetic analysis of the promoter region of the CD40L gene in primates and other mammals.

CD40L is a type II membrane protein comprised of 261 amino acids. CD40L plays a crucial role in the immune system where it is primarily expressed on activated T cells and triggers immunoglobulin class switching. The genetic disease X-linked hypergammaglobulinemia (HIGM1, XHIGM or XHIM) is caused by mutations in the CD40L gene. Individuals with HIGM1 are susceptible to recurrent infections to pathogens and a relationship has been shown to exist with malaria [Sabeti, P., Usen, S., Farhadian, S., Jallow, M., Doherty, T., Newport, M., Pinder, M., Ward, R., Kwiatkowski, D., 2002a. CD40L association with protection from severe malaria. Genes Immun. 3, 286-291]. In this paper, we phylogenetically examine the promoter region of CD40L in primates and other mammals via phylogenetic shadowing. This analysis revealed several regions of the CD40L promoter that were highly constrained and thereby inferred to be functional. These constrained regions confirmed many known regulatory sites. In addition, a novel, highly constrained upstream region was also identified which had an NF-AT recognition motif. These analyses also showed that the different mammal groups do not share an exactly similar set of promoter binding sites and taxon-specific promoters have evolved.

Primate molecular divergence dates.

With genomic data, alignments can be assembled that greatly increase the number of informative sites for analysis of molecular divergence dates. Here, we present an estimate of the molecular divergence dates for all of the major primate groups. These date estimates are based on a Bayesian analysis of approximately 59.8 kbp of genomic data from 13 primates and 6 mammalian outgroups, using a range of paleontologically supported calibration estimates. Results support a Cretaceous last common ancestor of extant primates (approximately 77 mya), an Eocene divergence between platyrrhine and catarrhine primates (approximately 43 mya), an Oligocene origin of apes and Old World monkeys (approximately 31 mya), and an early Miocene (approximately 18 mya) divergence of Asian and African great apes. These dates are examined in the context of other molecular clock studies.

Population history, biogeography, and taxonomy of orangutans (Genus: Pongo) based on a population genetic meta-analysis of multiple loci.

This paper examines orangutan population history and evolution through a meta-analysis of seven loci collected from both Sumatran and Bornean orangutans. Within orangutans, most loci show that the Sumatran population is about twice as diverse as the Bornean population. Orangutans are more diverse than African apes and humans. Sumatran and Bornean populations show significant genetic differentiation from one another and their history does not differ significantly from an 'island model' (population splitting without gene flow). Two different methods support a divergence of Bornean and Sumatran orangutans at 2.7-5 million years ago. This suggests that Pleistocene events, such as the cyclical exposure of the Sunda shelf and the Toba volcanic eruption, did not have a major impact on the divergence of Bornean and Sumatran orangutans. Pairwise mismatch analyses, however, suggest that Bornean orangutans have undergone a recent population expansion (beginning 39,000-64,000 years ago), while Sumatran orangutan populations were stable. Pleistocene events may have contributed to these aspects of orangutan population history. These conclusions are applied to the debate on orangutan taxonomy.

The phylogenetic and evolutionary history of a novel alpha-globin-type gene in orangutans (Pongo pygmaeus).

The alpha-globin genes are implicated in human resistance to malaria, a disease caused by Plasmodium parasites. This study is the first to analyze DNA sequences from a novel alpha-globin-type gene in orangutans, a species affected by Plasmodium. Phylogenetic methods show that the gene is a duplication of an alpha-globin gene and is located 5' of alpha-2 globin. The alpha-globin-type gene is notable for having four amino acid replacements relative to the orangutan's alpha-1 and alpha-2 globin genes, with no synonymous differences. Pairwise K(a)/K(s) methods and likelihood ratio tests (LRTs) revealed that the evolutionary history of the alpha-globin-type gene has been marked by either neutral or positive evolution, but not purifying selection. A comparative analysis of the amino acid replacements of the alpha-globin-type gene with human hemoglobinopathies and hemoglobin structure showed that two of the four replaced sites are members of the same molecular bond, one that is crucial to the proper functioning of the hemoglobin molecule. This suggested an adaptive evolutionary change. Functionally, this locus may result in a thalassemia-like phenotype in orangutans, possibly as an adaptation to combat Plasmodium.

The population genetics of the alpha-2 globin locus of orangutans (Pongo pygmaeus).

In this study, the molecular population genetics of the orangutan's alpha-2 globin (HBA2) gene were investigated in order to test for the action of natural selection. Haplotypes from 28 orangutan chromosomes were collected from a 1.46-kilobase region of the alpha-2 globin locus. While many aspects of the data were consistent with neutrality, the observed heterogeneous distribution of polymorphisms was inconsistent with neutral expectations. Furthermore, a single amino acid variant, found in both the Bornean and the Sumatran orangutan subspecies, was associated with different alternative synonymous variants in each subspecies, suggesting that the allele may have spread separately through the two subspecies after two distinct origination events. This variant is not in Hardy-Weinberg equilibrium (HWE). These observations are consistent with neutral models that incorporate population structure and models that invoke selection. The orangutan Plasmodium parasite is a plausible selective agent that may underlie the variation at alpha-2 globin in orangutans.

Genomic data support the hominoid slowdown and an Early Oligocene estimate for the hominoid-cercopithecoid divergence.

Several lines of indirect evidence suggest that hominoids (apes and humans) and cercopithecoids (Old World monkeys) diverged around 23-25 Mya. Importantly, although this range of dates has been used as both an initial assumption and as a confirmation of results in many molecular-clock analyses, it has not been critically assessed on its own merits. In this article we test the robusticity of the 23- to 25-Mya estimate with approximately 150,000 base pairs of orthologous DNA sequence data from two cercopithecoids and two hominoids by using quartet analysis. This method is an improvement over other estimates of the hominoid-cercopithecoid divergence because it incorporates two calibration points, one each within cercopithecoids and hominoids, and tests for a statistically appropriate model of molecular evolution. Most comparisons reject rate constancy in favor of a model incorporating two rates of evolution, supporting the "hominoid slowdown" hypothesis. By using this model of molecular evolution, the hominoid-cercopithecoid divergence is estimated to range from 29.2 to 34.5 Mya, significantly older than most previous analyses. Hominoid-cercopithecoid divergence dates of 23-25 Mya fall outside of the confidence intervals estimated, suggesting that as much as one-third of ape evolution has not been paleontologically sampled. Identifying stem cercopithecoids or hominoids from this period will be difficult because derived features that define crown catarrhines need not be present in early members of these lineages. More sites that sample primate habitats from the Oligocene of Africa are needed to better understand early ape and Old World monkey evolution.

New World monkey phylogeny based on X-linked G6PD DNA sequences.

The Platyrrhini, or New World monkeys, are an infraorder of Primates comprised of 16 genera. Molecular phylogenetic analyses have consistently sorted these genera into three groups: the Pitheciidae (e.g., saki and titi monkeys), Atelidae (e.g., spider and howler monkeys), and Cebidae (e.g., night monkeys, squirrel monkeys, and tamarins). No consensus has emerged on the relationships among the three groups or within the Cebidae. Here, approximately 0.8 kb of newly generated intronic DNA sequence data from the X-linked glucose-6-phosphate dehydrogenase (G6PD) locus have been collected from nine New World monkey taxa to examine these relationships. These data are added to 1.3 kb of previously generated G6PD intronic DNA sequence data [Mol. Phylogenet. Evol. 11 (1999) 459]. Using distance and parsimony-based techniques, G6PD sequences provide support for an initial bifurcation between the Pitheciidae and the remaining platyrrhines, linking Atelidae and Cebidae as sister taxa. Bayesian methods provided a conflicting phylogeny with Atelidae as outgroup. Within the Cebidae, a sister relation between Aotus and the Cebus/Saimiri clade is favored by parsimony analysis, but not by other analyses. Potential reasons for the difficulty in resolving family level New World monkey phylogenetics are discussed.

Genetic sex identification in orangutans.

To date, no established protocol for genetic sex identification in orangutans (Pongo pygmaeus) exists. In nearly all apes (gibbons, gorillas, chimpanzees, and humans), genetic sex identification is possible using the amelogenin gene because copies located on X and Y chromosomes have different sizes. Here we report that orangutan sex identification can be resolved through multiplex polymerase chain reaction (PCR) of the Y-linked SRY locus and the amelogenin locus. PCR amplifications of orangutan amelogenin produces one fragment size in both sexes, while SRY amplifies only in males. This protocol will allow primatologists to identify the sex of orangutans through genetic analysis.