Testing support for the northern and southern dispersal routes out of Africa: an analysis of Levantine and southern Arabian populations.

OBJECTIVES: The Northern Dispersal Route (NDR) and Southern Dispersal Route (SDR) are hypothesized to have been used by modern humans in the dispersal out of Africa. The NDR follows the Nile into Northeast Africa and crosses the Red Sea into the Levant. The SDR emerges from the Horn of Africa and crosses the Bab el-Mandeb into southern Arabia. In this study, we analyze genetic data from populations living along the NDR and SDR to test support for each dispersal route. MATERIALS AND METHODS: We genotyped 90 Yemeni samples on the Affymetrix Human Origins array. We analyzed these data with published data from Levantine and other southern Arabian populations as well as 157 comparative populations for a total sample size of >550,000 genetic variants from >2,000 individuals in >160 populations. We calculated outgroup f3 statistics to test how Levantine and southern Arabian populations relate to African populations living along the NDR and SDR and to other non-African populations. RESULTS: We find that Levantine and southern Arabian populations bear similar genetic relationships to both African and non-African populations, thus providing no support for the use of one dispersal route over the other. DISCUSSION: Our results are consistent with a history of gene flow between the Levant and southern Arabia. Consideration of genetic, archaeological, and paleoclimate data provide a slight edge for the SDR but, ultimately, more data are needed to definitively identify which dispersal route out of Africa was used.

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.

Comprehensive view of the population history of Arabia as inferred by mtDNA variation.

OBJECTIVES: Genetic and archaeological research supports the theory that Arabia was the first region traversed by modern humans as they left Africa and dispersed throughout Eurasia. However, the role of Arabia from the initial migration out of Africa until more recent times is still unclear. MATERIALS AND METHODS: We have generated 379 new hypervariable segment 1 (HVS-1) sequences from a range of geographic locations throughout Yemen. We compare these data to published HVS-1 sequences representing Arabia and neighboring regions to build a unique dataset of 186 populations and 14,290 sequences. RESULTS: We identify 4,563 haplotypes unevenly distributed across Arabia and neighboring regions. Arabia contains higher proportions of shared haplotypes than the regions with which it shares these haplotypes, suggesting high levels of migration through the region. Populations in Arabia show higher levels of population expansion than those in East Africa, but lower levels than the Near East, Middle East or India. Arabian populations also show very high levels of genetic variation that overlaps with variation from most other regions. CONCLUSION: We take a population genetics approach to provide a comprehensive view of the relationships of Arabian and neighboring populations. We show that Arabian populations share closest links to the Near East and North Africa, but have a more ancient origin with slower demographic growth and/or lower migration rates. Our conclusions are supported by phylogenetic studies but also suggest that recent migrations have erased signals of earlier events.

Bayesian analyses of Yemeni mitochondrial genomes suggest multiple migration events with Africa and Western Eurasia.

OBJECTIVES: Anatomically, modern humans are thought to have migrated out of Africa ∼60,000 years ago in the first successful global dispersal. This initial migration may have passed through Yemen, a region that has experienced multiple migrations events with Africa and Eurasia throughout human history. We use Bayesian phylogenetics to determine how ancient and recent migrations have shaped Yemeni mitogenomic variation. MATERIALS AND METHODS: We sequenced 113 mitogenomes from multiple Yemeni regions with a focus on haplogroups M, N, and L3(xM,N) as these groups have the oldest evolutionary history outside of Africa. We performed Bayesian evolutionary analyses to generate time-measured phylogenies calibrated by Neanderthal and Denisovan mitogenomes in order to determine the age of Yemeni-specific clades. RESULTS: As defined by Yemeni monophyly, Yemeni in situ evolution is limited to the Holocene or latest Pleistocene (ages of clades in subhaplogroups L3b1a1a, L3h2, L3x1, M1a1f, M1a5, N1a1a3, and N1a3 range from 2 to 14 kya) and is often situated within broader Horn of Africa/southern Arabia in situ evolution (L3h2, L3x1, M1a1f, M1a5, and N1a1a3 ages range from 7 to 29 kya). Five subhaplogroups show no monophyly and are candidates for Holocene migration into Yemen (L0a2a2a, L3d1a1a, L3i2, M1a1b, and N1b1a). DISCUSSION: Yemeni mitogenomes are largely the product of Holocene migration, and subsequent in situ evolution, from Africa and western Eurasia. However, we hypothesize that recent population movements may obscure the genetic signature of more ancient migrations. Additional research, e.g., analyses of Yemeni nuclear genetic data, is needed to better reconstruct the complex population and migration histories associated with Out of Africa.

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.

Internal diversification of mitochondrial haplogroup R0a reveals post-last glacial maximum demographic expansions in South Arabia.

Widespread interest in the first successful Out of Africa dispersal of modern humans ∼60-80 thousand years ago via a southern migration route has overshadowed the study of later periods of South Arabian prehistory. In this work, we show that the post-Last Glacial Maximum period of the past 20,000 years, during which climatic conditions were becoming more hospitable, has been a significant time in the formation of the extant genetic composition and population structure of this region. This conclusion is supported by the internal diversification displayed in the highly resolved phylogenetic tree of 89 whole mitochondrial genomes (71 being newly presented here) for haplogroup R0a-the most frequent and widespread haplogroup in Arabia. Additionally, two geographically specific clades (R0a1a1a and R0a2f1) have been identified in non-Arabic speaking peoples such as the Soqotri and Mahri living in the southern part of the Arabian Peninsula where a past refugium was identified by independent archaeological studies. Estimates of time to the most recent common ancestor of these lineages match the earliest archaeological evidence for seafaring activity in the peninsula in the sixth millennium BC.

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.

Population history of the Red Sea--genetic exchanges between the Arabian Peninsula and East Africa signaled in the mitochondrial DNA HV1 haplogroup.

Archaeological studies have revealed cultural connections between the two sides of the Red Sea dating to prehistory. The issue has still not been properly addressed, however, by archaeogenetics. We focus our attention here on the mitochondrial haplogroup HV1 that is present in both the Arabian Peninsula and East Africa. The internal variation of 38 complete mitochondrial DNA sequences (20 of them presented here for the first time) affiliated into this haplogroup testify to its emergence during the late glacial maximum, most probably in the Near East, with subsequent dispersion via population expansions when climatic conditions improved. Detailed phylogeography of HV1 sequences shows that more recent demographic upheavals likely contributed to their spread from West Arabia to East Africa, a finding concordant with archaeological records suggesting intensive maritime trade in the Red Sea from the sixth millennium BC onwards. Closer genetic exchanges are apparent between the Horn of Africa and Yemen, while Egyptian HV1 haplotypes seem to be more similar to the Near Eastern ones.

Type II Diabetes Mellitus and impaired glucose tolerance in Yemen: prevalence, associated metabolic changes and risk factors.

OBJECTIVE: To investigate the prevalence of type II Diabetes Mellitus (DM) and impaired glucose tolerance (IGT) and identify the metabolic abnormalities and risk factors associated with these conditions in an urban city of Yemen. RESEARCH DESIGN AND METHODS: Cross-sectional, population-based study investigating 498 adults (245 males and 253 females) aged 25-65 years. The 1999 modified World Health Organization criteria were adopted for the diagnosis of Diabetes Mellitus and IGT. A standard questionnaire was applied and blood lipids, blood pressure, body mass index (BMI) and waist/hip ratio (WHR) were determined. RESULTS: The overall prevalence of type II Diabetes Mellitus was 4.6% (7.4% in males and 2% in females). Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were found in 2% and 2.2% of the study population. Factors independently related to any abnormality in glucose tolerance, using logistic regression analysis, were sex, hyperlipidaemia, hypertriglyceridaemia, and hypertension; whereas sex and age related to DM. More than 80% of the type II diabetics were over the age of 40, 35% being hyperlipidaemic, 22% being hypertensive and 18% obese. Sixty percent of IGT subjects were hyperlipidaemic and 20% were obese. Approximately 78% of obese individuals (>/=30 kg/m(2)) had normal glucose tolerance. CONCLUSION: The prevalence of type II DM and its potential increase reflected by the high prevalence of obesity in normal glucose tolerance subjects in the Yemeni population constitutes a major public health problem.

Human migration patterns in Yemen and implications for reconstructing prehistoric population movements.

Population migration has played an important role in human evolutionary history and in the patterning of human genetic variation. A deeper and empirically-based understanding of human migration dynamics is needed in order to interpret genetic and archaeological evidence and to accurately reconstruct the prehistoric processes that comprise human evolutionary history. Current empirical estimates of migration include either short time frames (i.e. within one generation) or partial knowledge about migration, such as proportion of migrants or distance of migration. An analysis of migration that includes both proportion of migrants and distance, and direction over multiple generations would better inform prehistoric reconstructions. To evaluate human migration, we use GPS coordinates from the place of residence of the Yemeni individuals sampled in our study, their birthplaces and their parents' and grandparents' birthplaces to calculate the proportion of migrants, as well as the distance and direction of migration events between each generation. We test for differences in these values between the generations and identify factors that influence the probability of migration. Our results show that the proportion and distance of migration between females and males is similar within generations. In contrast, the proportion and distance of migration is significantly lower in the grandparents' generation, most likely reflecting the decreasing effect of technology. Based on our results, we calculate the proportion of migration events (0.102) and mean and median distances of migration (96 km and 26 km) for the grandparent's generation to represent early times in human evolution. These estimates can serve to set parameter values of demographic models in model-based methods of prehistoric reconstruction, such as approximate Bayesian computation. Our study provides the first empirically-based estimates of human migration over multiple generations in a developing country and these estimates are intended to enable more precise reconstruction of the demographic processes that characterized human evolution.

Association of adipokines, leptin/adiponectin ratio and C-reactive protein with obesity and type 2 diabetes mellitus.

OBJECTIVE: Alterations in plasma adipokines and/or inflammatory parameters in Type 2 DM remain vague as to whether they are due to obesity and/or directly associated with the diabetic state. Our objective was to compare plasma adiponectin, leptin, leptin/adiponectin ratio (LAR) and hs-CRP in obese non-diabetic subjects and non-obese Type 2 DM patients, as well as determining the association of these adipokines with MetS and diabetes-related quantitative traits. METHODS: In this study, 92 Yemeni male volunteers aged 25-60 years old were enrolled, 31 of whom were healthy subjects with BMI < 25 kg/m(2) served as control; 30 non-diabetic obese subjects BMI ≥ 30 kg/m(2) and FBG < 6.1 mmol/l; and 31 non-obese Type 2 DM with FBG > 7 mmol/l and BMI < 25 kg/m(2). RESULTS: Adiponectin was lower in obese subjects, with no differences between non-obese Type 2 DM patients and controls. In contrast, leptin, LAR and hs-CRP were higher in both obese subjects and non-obese Type 2 DM patients. Linear regression analysis showed adiponectin to be associated negatively with BMI, waist circumference, insulin, HOMA-ß and HOMA-IR; whereas leptin, LAR and hs-CRP were associated positively with BMI, waist circumference, TG, FBG, insulin, HOMA-ß and HOMA-IR. Moreover, adiponectin negatively correlated with leptin, LAR and hs-CRP; whereas leptin and LAR positively correlated with hs-CRP and with each other. CONCLUSION: Plasma adiponectin is not affected by diabetes per se, suggesting that its alterations in Type 2 DM may be due to obesity and may be an important link between adiposity, IR and Type 2 DM.

Relationship between total homocysteine, total cholesterol and creatinine levels in overt hypothyroid patients.

Hypothyroidism is associated with an increased risk for cardiovascular disease, which can not be fully explained by the atherogenic lipid profile, particularly total cholesterol and LDL-C, and other pathogenic factors may be involved. Plasma total homocysteine (tHcy) is an independent risk factor for cardiovascular disease and accelerated atherosclerosis. The aim of this study was to investigate the serum total homocysteine (tHcy) levels and its relation to total cholesterol, creatinine and thyroid hormones fT3, fT4 and TSH levels in overt hypothyroid patients compared to control subjects. In this study thirty recently diagnosed, non-treated overt hypothyroid patients (f=27, m=3) and twenty normal volunteers control (f=18, m=2) were included and subjected to determination of serum tHcy by enzyme immunoassay (EIA) technique, fT3, fT4 and TSH by Elecsys cobas e 601 analyzer, total cholesterol by enzymatic method and creatinine by kinetic method. The data was statistically analysed by SPSS-10 and p values less than 0.05 were considered significant.Our results showed that there were a significant increase of tHcy, TSH, T.cholesterol and creatinine levels by 113%, 12-folds, 58% and 54%, respectively, and a significant decrease of fT4 and fT3 levels by 49.6% and 56.4% , respectively, in hypothyroid patients than in control group. For tHcy (Mean±SD, 24.45±5.50 µmol/l vs 11.48±3.03 µmol/l, respectively; P < 0.001). tHcy was significantly positively correlated with TSH, creatinine and age and negatively correlated with free thyroxine (fT4) and no significant correlations with fT3 and T.cholesterol. In conclusion, our study confirmed the observation of elevated serum tHcy, T.cholesterol and creatinine in overt hypothyroidism and the presence of an inverse relation between tHcy with fT4 and a positive relation with TSH.

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.