Entwined African and Asian genetic roots of medieval peoples of the Swahili coast.

The urban peoples of the Swahili coast traded across eastern Africa and the Indian Ocean and were among the first practitioners of Islam among sub-Saharan people1,2. The extent to which these early interactions between Africans and non-Africans were accompanied by genetic exchange remains unknown. Here we report ancient DNA data for 80 individuals from 6 medieval and early modern (AD 1250-1800) coastal towns and an inland town after AD 1650. More than half of the DNA of many of the individuals from coastal towns originates from primarily female ancestors from Africa, with a large proportion-and occasionally more than half-of the DNA coming from Asian ancestors. The Asian ancestry includes components associated with Persia and India, with 80-90% of the Asian DNA originating from Persian men. Peoples of African and Asian origins began to mix by about AD 1000, coinciding with the large-scale adoption of Islam. Before about AD 1500, the Southwest Asian ancestry was mainly Persian-related, consistent with the narrative of the Kilwa Chronicle, the oldest history told by people of the Swahili coast3. After this time, the sources of DNA became increasingly Arabian, consistent with evidence of growing interactions with southern Arabia4. Subsequent interactions with Asian and African people further changed the ancestry of present-day people of the Swahili coast in relation to the medieval individuals whose DNA we sequenced.

Automated morphological phenotyping using learned shape descriptors and functional maps: A novel approach to geometric morphometrics.

The methods of geometric morphometrics are commonly used to quantify morphology in a broad range of biological sciences. The application of these methods to large datasets is constrained by manual landmark placement limiting the number of landmarks and introducing observer bias. To move the field forward, we need to automate morphological phenotyping in ways that capture comprehensive representations of morphological variation with minimal observer bias. Here, we present Morphological Variation Quantifier (morphVQ), a shape analysis pipeline for quantifying, analyzing, and exploring shape variation in the functional domain. morphVQ uses descriptor learning to estimate the functional correspondence between whole triangular meshes in lieu of landmark configurations. With functional maps between pairs of specimens in a dataset we can analyze and explore shape variation. morphVQ uses Consistent ZoomOut refinement to improve these functional maps and produce a new representation of shape variation, area-based and conformal (angular) latent shape space differences (LSSDs). We compare this new representation of shape variation to shape variables obtained via manual digitization and auto3DGM, an existing approach to automated morphological phenotyping. We find that LSSDs compare favorably to modern 3DGM and auto3DGM while being more computationally efficient. By characterizing whole surfaces, our method incorporates more morphological detail in shape analysis. We can classify known biological groupings, such as Genus affiliation with comparable accuracy. The shape spaces produced by our method are similar to those produced by modern 3DGM and to auto3DGM, and distinctiveness functions derived from LSSDs show us how shape variation differs between groups. morphVQ can capture shape in an automated fashion while avoiding the limitations of manually digitized landmarks, and thus represents a novel and computationally efficient addition to the geometric morphometrics toolkit.

Ecomorphological analysis of bovid mandibles from Laetoli Tanzania using 3D geometric morphometrics: Implications for hominin paleoenvironmental reconstruction.

The current study describes a new method of mandibular ecological morphology (ecomorphology). Three-dimensional geometric morphometrics (3D GM) was used to quantify mandibular shape variation between extant bovids with different feeding preferences. Landmark data were subjected to generalized Procrustes analysis (GPA), principal components analysis (PCA), and discriminant function analysis (DFA). The PCA resulted in a continuum from grazers to browsers along PC1 and DFA classified 88% or more of the modern specimens to the correct feeding category. The protocol was reduced to a subset of landmarks on the mandibular corpus in order to make it applicable to incomplete fossils. The reduced landmark set resulted in greater overlap between feeding categories but maintained the same continuum as the complete landmark model. The DFA resubstitution and jackknife analyses resulted in classification success rates of 85% and 80%, respectively. The reduced landmark model was applied to fossil mandibles from the Upper Laetolil Beds (∼4.3-3.5 Ma) and Upper Ndolanya Beds (∼2.7-2.6 Ma) at Laetoli, Tanzania in order to assess antelope diet, and indirectly evaluate paleo-vegetation structure. The majority of the fossils were classified by the DFA as browsers or mixed feeders preferring browse. Our results indicate a continuous presence of wooded habitats and are congruent with recent environmental studies at Laetoli indicating a mosaic woodland-bushland-grassland savanna ecosystem.

Early back-to-Africa migration into the Horn of Africa.

Genetic studies have identified substantial non-African admixture in the Horn of Africa (HOA). In the most recent genomic studies, this non-African ancestry has been attributed to admixture with Middle Eastern populations during the last few thousand years. However, mitochondrial and Y chromosome data are suggestive of earlier episodes of admixture. To investigate this further, we generated new genome-wide SNP data for a Yemeni population sample and merged these new data with published genome-wide genetic data from the HOA and a broad selection of surrounding populations. We used multidimensional scaling and ADMIXTURE methods in an exploratory data analysis to develop hypotheses on admixture and population structure in HOA populations. These analyses suggested that there might be distinct, differentiated African and non-African ancestries in the HOA. After partitioning the SNP data into African and non-African origin chromosome segments, we found support for a distinct African (Ethiopic) ancestry and a distinct non-African (Ethio-Somali) ancestry in HOA populations. The African Ethiopic ancestry is tightly restricted to HOA populations and likely represents an autochthonous HOA population. The non-African ancestry in the HOA, which is primarily attributed to a novel Ethio-Somali inferred ancestry component, is significantly differentiated from all neighboring non-African ancestries in North Africa, the Levant, and Arabia. The Ethio-Somali ancestry is found in all admixed HOA ethnic groups, shows little inter-individual variance within these ethnic groups, is estimated to have diverged from all other non-African ancestries by at least 23 ka, and does not carry the unique Arabian lactase persistence allele that arose about 4 ka. Taking into account published mitochondrial, Y chromosome, paleoclimate, and archaeological data, we find that the time of the Ethio-Somali back-to-Africa migration is most likely pre-agricultural.

Primate phylogenetic relationships and divergence dates inferred from complete mitochondrial genomes.

The origins and the divergence times of the most basal lineages within primates have been difficult to resolve mainly due to the incomplete sampling of early fossil taxa. The main source of contention is related to the discordance between molecular and fossil estimates: while there are no crown primate fossils older than 56Ma, most molecule-based estimates extend the origins of crown primates into the Cretaceous. Here we present a comprehensive mitogenomic study of primates. We assembled 87 mammalian mitochondrial genomes, including 62 primate species representing all the families of the order. We newly sequenced eleven mitochondrial genomes, including eight Old World monkeys and three strepsirrhines. Phylogenetic analyses support a strong topology, confirming the monophyly for all the major primate clades. In contrast to previous mitogenomic studies, the positions of tarsiers and colugos relative to strepsirrhines and anthropoids are well resolved. In order to improve our understanding of how fossil calibrations affect age estimates within primates, we explore the effect of seventeen fossil calibrations across primates and other mammalian groups and we select a subset of calibrations to date our mitogenomic tree. The divergence date estimates of the Strepsirrhine/Haplorhine split support an origin of crown primates in the Late Cretaceous, at around 74Ma. This result supports a short-fuse model of primate origins, whereby relatively little time passed between the origin of the order and the diversification of its major clades. It also suggests that the early primate fossil record is likely poorly sampled.

Characterization of human cortical gene expression in relation to glucose utilization.

OBJECTIVES: Human brain development follows a unique pattern characterized by a prolonged period of postnatal growth and reorganization, and a postnatal peak in glucose utilization. The molecular processes underlying these developmental changes are poorly characterized. The objectives of this study were to determine developmental trajectories of gene expression and to examine the evolutionary history of genes differentially expressed as a function of age. METHODS: We used microarrays to determine age-related patterns of mRNA expression in human cerebral cortical samples ranging from infancy to adulthood. In contrast to previous developmental gene expression studies of human neocortex that relied on postmortem tissue, we measured mRNA expression from the nondiseased margins of surgically resected tissue. We used regression models designed to identify transcripts that followed significant linear or curvilinear functions of age and used population genetics techniques to examine the evolution of these genes. RESULTS: We identified 40 transcripts with significant age-related trajectories in expression. Ten genes have documented roles in nervous system development and energy metabolism, others are novel candidates in brain development. Sixteen transcripts showed similar patterns of expression, characterized by decreasing expression during childhood. Comparative genomic analyses revealed that the regulatory regions of three genes have evidence of adaptive evolution in recent human evolution. CONCLUSIONS: These findings provide evidence that a subset of genes expressed in the human cerebral cortex broadly mirror developmental patterns of cortical glucose consumption. Whether there is a causal relationship between gene expression and glucose utilization remains to be determined.

Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection.

Differentiated cells possess a remarkable genomic plasticity that can be manipulated to reverse or change developmental commitments. Here, we show that the leprosy bacterium hijacks this property to reprogram adult Schwann cells, its preferred host niche, to a stage of progenitor/stem-like cells (pSLC) of mesenchymal trait by downregulating Schwann cell lineage/differentiation-associated genes and upregulating genes mostly of mesoderm development. Reprogramming accompanies epigenetic changes and renders infected cells highly plastic, migratory, and immunomodulatory. We provide evidence that acquisition of these properties by pSLC promotes bacterial spread by two distinct mechanisms: direct differentiation to mesenchymal tissues, including skeletal and smooth muscles, and formation of granuloma-like structures and subsequent release of bacteria-laden macrophages. These findings support a model of host cell reprogramming in which a bacterial pathogen uses the plasticity of its cellular niche for promoting dissemination of infection and provide an unexpected link between cellular reprogramming and host-pathogen interaction.

Culture modifies expectations of kinship and sex-biased dispersal patterns: a case study of patrilineality and patrilocality in tribal Yemen.

Studies of the impact of post-marital residence patterns on the distribution of genetic variation within populations have returned conflicting results. These studies have generally examined genetic diversity within and between groups with different post-marriage residence patterns. Here, we directly examine Y chromosome microsatellite variation in individuals carrying a chromosome in the same Y haplogroup. We analyze Y chromosome data from two samples of Yemeni males: a sample representing the entire country and a sample from a large highland village. Our results support a normative patrilocality in highland Yemeni tribal populations, but also suggest that patrilocality is violated often enough to break down the expected correlation of genetic and geographic distance. We propose that a great deal of variation in male dispersal distance distributions is subsumed under the "patrilocal" label and that few human societies are likely to realize the idealized male dispersal distribution expected under strict patrilocality. In addition, we found almost no specific correspondence between social kinship and genetic patriline at the level of the clan (large, extended patrilineal kinship group) within a large, highland Yemeni village. We discuss ethnographic accounts that offer several cultural practices that explain exceptions to patrilocality and means by which social kinship and genetic patriline may become disentangled.

Genetic signatures of a demographic collapse in a large-bodied forest dwelling primate (Mandrillus leucophaeus).

It is difficult to predict how current climate change will affect wildlife species adapted to a tropical rainforest environment. Understanding how population dynamics fluctuated in such species throughout periods of past climatic change can provide insight into this issue. The drill (Mandrillus leucophaeus) is a large-bodied rainforest adapted mammal found in West Central Africa. In the middle of this endangered monkey's geographic range is Lake Barombi Mbo, which has a well-documented palynological record of environmental change that dates to the Late Pleistocene. We used a Bayesian coalescent-based framework to analyze 2,076 base pairs of mitochondrial DNA across wild drill populations to infer past changes in female effective population size since the Late Pleistocene. Our results suggest that the drill underwent a nearly 15-fold demographic collapse in female effective population size that was most prominent during the Mid Holocene (approximately 3-5 Ka). This time period coincides with a period of increased dryness and seasonality across Africa and a dramatic reduction in forest coverage at Lake Barombi Mbo. We believe that these changes in climate and forest coverage were the driving forces behind the drill population decline. Furthermore, the warm temperatures and increased aridity of the Mid Holocene are potentially analogous to current and future conditions faced by many tropical rainforest communities. In order to prevent future declines in population size in rainforest-adapted species such as the drill, large tracts of forest should be protected to both preserve habitat and prevent forest loss through aridification.

Dynamic gene expression in the human cerebral cortex distinguishes children from adults.

In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR ~/= 0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development.

Mitochondrial DNA reveals distinct evolutionary histories for Jewish populations in Yemen and Ethiopia.

Southern Arabia and the Horn of Africa are important geographic centers for the study of human population history because a great deal of migration has characterized these regions since the first emergence of humans out of Africa. Analysis of Jewish groups provides a unique opportunity to investigate more recent population histories in this area. Mitochondrial DNA is used to investigate the maternal evolutionary history and can be combined with historical and linguistic data to test various population histories. In this study, we assay mitochondrial control region DNA sequence and diagnostic coding variants in Yemenite (n = 45) and Ethiopian (n = 41) Jewish populations, as well as in neighboring non-Jewish Yemeni (n = 50) and Ethiopian (previously published Semitic speakers) populations. We investigate their population histories through a comparison of haplogroup distributions and phylogenetic networks. A high frequency of sub-Saharan African L haplogroups was found in both Jewish populations, indicating a significant African maternal contribution unlike other Jewish Diaspora populations. However, no identical haplotypes were shared between the Yemenite and Ethiopian Jewish populations, suggesting very little gene flow between the populations and potentially distinct maternal population histories. These new data are also used to investigate alternate population histories in the context of historical and linguistic data. Specifically, Yemenite Jewish mitochondrial diversity reflects potential descent from ancient Israeli exiles and shared African and Middle Eastern ancestry with little evidence for large-scale conversion of local Yemeni. In contrast, the Ethiopian Jewish population appears to be a subset of the larger Ethiopian population suggesting descent primarily through conversion of local women.

Efficient population assignment and outlier detection in human populations using biallelic markers chosen by principal component-based rankings.

Whole-genome studies of genetic variation are now performed routinely and have accelerated the identification of disease-associated allelic variants, positive selection, recombination, and structural variation. However, these studies are sensitive to the presence of outlier data from individuals of different ancestry than the rest of the sample. Currently, the most common method of excluding outlier individuals is to collect a population sample and exclude outliers after genome-wide data have been collected. Here we show that a small collection of 20-27 polymorphic Alu insertions, selected using a principal component-based method with genetic ancestry estimates, may be used to easily assign Africans, East Asians, and Europeans to their population of origin. In addition, we show that samples from a geographically and genetically intermediate population (in our study, samples from India) can be identified within the original sample of Africans, East Asians, and Europeans. Finally, we show that outlier individuals from neighboring geographic regions (in our study, Yemen and sub-Saharan Africa) can be identified. These results will be of value in preselection of samples for more in-depth analysis as well as customized identification of maximally informative polymorphic markers for regional studies.

Successive radiations, not stasis, in the South American primate fauna.

The earliest Neotropical primate fossils complete enough for taxonomic assessment, Dolichocebus, Tremacebus, and Chilecebus, date to approximately 20 Ma. These have been interpreted as either closely related to extant forms or as extinct stem lineages. The former hypothesis of morphological stasis requires most living platyrrhine genera to have diverged before 20 Ma. To test this hypothesis, we collected new complete mitochondrial genomes from Aotus lemurinus, Saimiri sciureus, Saguinus oedipus, Ateles belzebuth, and Callicebus donacophilus. We combined these with published sequences from Cebus albifrons and other primates to infer the mitochondrial phylogeny. We found support for a cebid/atelid clade to the exclusion of the pitheciids. Then, using Bayesian methods and well-supported fossil calibration constraints, we estimated that the platyrrhine most recent common ancestor (MRCA) dates to 19.5 Ma, with all major lineages diverging by 14.3 Ma. Next, we estimated catarrhine divergence dates on the basis of platyrrhine divergence scenarios and found that only a platyrrhine MRCA less than 21 Ma is concordant with the catarrhine fossil record. Finally, we calculated that 33% more change in the rate of evolution is required for platyrrhine divergences consistent with the morphologic stasis hypothesis than for a more recent radiation. We conclude that Dolichocebus, Tremacebus, and Chilecebus are likely too old to be crown platyrrhines, suggesting they were part of an extinct early radiation. We note that the crown platyrrhine radiation was concomitant with the radiation of 2 South American xenarthran lineages and follows a global temperature peak and tectonic activity in the Andes.

Demographic changes and marker properties affect detection of human population differentiation.

BACKGROUND: Differentiating genetically between populations is valuable for admixture and population stratification detection and in understanding population history. This is easy to achieve for major continental populations, but not for closely related populations. It has been claimed that a large marker panel is necessary to reliably distinguish populations within a continent. We investigated whether empirical genetic differentiation could be accomplished efficiently among three Asian populations (Hmong, Thai, and Chinese) using a small set of highly variable markers (15 tetranucleotide and 17 dinucleotide repeats). RESULTS: Hmong could be differentiated from Thai and Chinese based on multi-locus genotypes, but Thai and Chinese were indistinguishable from each other. We found significant evidence for a recent population bottleneck followed by expansion in the Hmong that was not present in the Thai or Chinese. Tetranucleotide repeats were less useful than dinucleotide repeat markers in distinguishing between major continental populations (Asian, European, and African) while both successfully distinguished Hmong from Thai and Chinese. CONCLUSION: Demographic history contributes significantly to robust detection of intracontinental population structure. Populations having experienced a rapid size reduction may be reliably distinguished as a result of a genetic drift -driven redistribution of population allele frequencies. Tetranucleotide markers, which differ from dinucleotide markers in mutation mechanism and rate, are similar in information content to dinucleotide markers in this situation. These factors should be considered when identifying populations suitable for gene mapping studies and when interpreting interpopulation relationships based on microsatellite markers.

Mitochondrial data support an odd-nosed colobine clade.

To obtain a more complete understanding of the evolutionary history of the leaf-eating monkeys we have examined the mitochondrial genome sequence of two African and six Asian colobines. Although taxonomists have proposed grouping the "odd-nosed" colobines (proboscis monkey, douc langur, and the snub-nosed monkey) together, phylogenetic support for such a clade has not been tested using molecular data. Phylogenetic analyses using parsimony, maximum likelihood, and Bayesian methods support a monophyletic clade of odd-nosed colobines consisting of Nasalis, Pygathrix, and Rhinopithecus, with tentative support for Nasalis occupying a basal position within this clade. The African and Asian colobine lineages are inferred to have diverged by 10.8 million years ago (mya or Ma). Within the Asian colobines the odd-nosed clade began to diversify by 6.7 Ma. These results augment our understanding of colobine evolution, particularly the nature and timing of the colobine expansion into Asia. This phylogenetic information will aid those developing conservation strategies for these highly endangered, diverse, and unique primates.

Catarrhine primate divergence dates estimated from complete mitochondrial genomes: concordance with fossil and nuclear DNA evidence.

Accurate divergence date estimates improve scenarios of primate evolutionary history and aid in interpretation of the natural history of disease-causing agents. While molecule-based estimates of divergence dates of taxa within the superfamily Hominoidea (apes and humans) are common in the literature, few such estimates are available for the Cercopithecoidea (Old World monkeys), the sister taxon of the hominoids in the primate infraorder Catarrhini. To help fill this gap, we have sequenced the entire mitochondrial DNA (mtDNA) genomes from a representative of three cercopithecoid tribes, Cercopithecini (Chlorocebus aethiops), Colobini (Colobus guereza), and Presbytini (Trachypithecus obscurus), and analyzed these new data together with other catarrhine mtDNA genomes available in public databases. Molecular divergence date estimates are dependent on calibration points gleaned from the paleontological record. We defined criteria for the selection of good calibration points and identified three points meeting these criteria: Homo-Pan, 6.0 Ma; Pongo-hominines, 14.0 Ma; hominoid/cercopithecoid, 23.0 Ma. Because a uniform molecular clock does not fit the catarrhine mtDNA data, we estimated divergence dates using a penalized likelihood and a Bayesian method, both of which take into account the effects of rate differences on lineages, phylogenetic tree structure, and multiple calibration points. The penalized likelihood method applied to the coding regions of the mtDNA genome yielded the following divergence date estimates, with approximate 95% confidence intervals: cercopithecine-colobine, 16.2 (14.4-17.9) Ma; colobin-presbytin, 10.9 (9.6-12.3) Ma; cercopithecin-papionin, 11.6 (10.3-12.9) Ma; and Macaca-Papio, 9.8 (8.6-10.9) Ma. Within the hominoids, the following dates were inferred: hylobatid-hominid, 16.8 (15.0-18.5) Ma; Gorilla-Homo+Pan, 8.1 (7.1-9.0) Ma; Pongo pygmaeus pygmaeus-P. p. abelii, 4.1 (3.5-4.7) Ma; and Pan troglodytes-P. paniscus, 2.4 (2.0-2.7) Ma. These dates were similar to those found using penalized likelihood on other subsets of the data, but slightly younger than several of the Bayesian estimates.