Diverse Human Populations Research Articles

Metabolic diversity in human populations and correlation with genetic and ancestral geographic distances.

DNA polymorphic markers and self-defined ethnicity groupings are used to group individuals with shared ancient geographic ancestry. Here we studied whether ancestral relationships between individuals could be identified from metabolic screening data reported by the California newborn screening (NBS) program. NBS data includes 41 blood metabolites measured by tandem mass spectrometry from singleton babies in 17 parent-reported ethnicity groupings. Ethnicity-associated differences identified for 71% of NBS metabolites (29 of 41, Cohen's d > 0.5) showed larger differences in blood levels of acylcarnitines than of amino acids (P < 1e-4). A metabolic distance measure, developed to compare ethnic groupings based on metabolic differences, showed low positive correlation with genetic and ancient geographic distances between the groups' ancestral world populations. Several outlier group pairs were identified with larger genetic and smaller metabolic distances (Black versus White) or with smaller genetic and larger metabolic distances (Chinese versus Japanese) indicating the influence of genetic and of environmental factors on metabolism. Using machine learning, comparison of metabolic profiles between all pairs of ethnic groupings distinguished individuals with larger genetic distance (Black versus Chinese, AUC = 0.96), while genetically more similar individuals could not be separated metabolically (Hispanic versus Native American, AUC = 0.51). Additionally, we identified metabolites informative for inferring metabolic ancestry in individuals from genetically similar populations, which included biomarkers for inborn metabolic disorders (C10:1, C12:1, C3, C5OH, Leucine-Isoleucine). This work sheds new light on metabolic differences in healthy newborns in diverse populations, which could have implications for improving genetic disease screening.

Function and Constraint in Enhancer Sequences with Multiple Evolutionary Origins.

Thousands of human gene regulatory enhancers are composed of sequences with multiple evolutionary origins. These evolutionarily "complex" enhancers consist of older "core" sequences and younger "derived" sequences. However, the functional relationship between the sequences of different evolutionary origins within complex enhancers is poorly understood. We evaluated the function, selective pressures, and sequence variation across core and derived components of human complex enhancers. We find that both components are older than expected from the genomic background, and complex enhancers are enriched for core and derived sequences of similar evolutionary ages. Both components show strong evidence of biochemical activity in massively parallel report assays. However, core and derived sequences have distinct transcription factor (TF)-binding preferences that are largely similar across evolutionary origins. As expected, given these signatures of function, both core and derived sequences have substantial evidence of purifying selection. Nonetheless, derived sequences exhibit weaker purifying selection than adjacent cores. Derived sequences also tolerate more common genetic variation and are enriched compared with cores for expression quantitative trait loci associated with gene expression variability in human populations. In conclusion, both core and derived sequences have strong evidence of gene regulatory function, but derived sequences have distinct constraint profiles, TF-binding preferences, and tolerance to variation compared with cores. We propose that the step-wise integration of younger derived with older core sequences has generated regulatory substrates with robust activity and the potential for functional variation. Our analyses demonstrate that synthesizing study of enhancer evolution and function can aid interpretation of regulatory sequence activity and functional variation across human populations.

Genome-wide detection of human variants that disrupt intronic branchpoints.

Pre-messenger RNA splicing is initiated with the recognition of a single-nucleotide intronic branchpoint (BP) within a BP motif by spliceosome elements. Forty-eight rare variants in 43 human genes have been reported to alter splicing and cause disease by disrupting BP. However, until now, no computational approach was available to efficiently detect such variants in massively parallel sequencing data. We established a comprehensive human genome-wide BP database by integrating existing BP data and generating new BP data from RNA sequencing of lariat debranching enzyme DBR1-mutated patients and from machine-learning predictions. We characterized multiple features of BP in major and minor introns and found that BP and BP-2 (two nucleotides upstream of BP) positions exhibit a lower rate of variation in human populations and higher evolutionary conservation than the intronic background, while being comparable to the exonic background. We developed BPHunter as a genome-wide computational approach to systematically and efficiently detect intronic variants that may disrupt BP recognition. BPHunter retrospectively identified 40 of the 48 known pathogenic BP variants, in which we summarized a strategy for prioritizing BP variant candidates. The remaining eight variants all create AG-dinucleotides between the BP and acceptor site, which is the likely reason for missplicing. We demonstrated the practical utility of BPHunter prospectively by using it to identify a novel germline heterozygous BP variant of STAT2 in a patient with critical COVID-19 pneumonia and a novel somatic intronic 59-nucleotide deletion of ITPKB in a lymphoma patient, both of which were validated experimentally. BPHunter is publicly available from https://hgidsoft.rockefeller.edu/BPHunter and https://github.com/casanova-lab/BPHunter.

Dental morphological variation in Chalcolithic and Bronze Age human populations from North-Eastern Romania

BackgroundThis study aims to evaluate the dental variability and the phenetic relationships among archaeological human populations of the Chalcolithic and Bronze Age in North-Eastern Romania. MethodsThe evaluation of phenotypic variability was performed using the 2D Geometric Morphometrics on the second molars (upper – M2, and lower – M2) belonging to adult skeletons discovered in archaeological sites of the Chalcolithic and Bronze Age in North-Eastern Romania. ResultsThe size (Centroid Size, CS) and shape analysis of the second molar highlighted specific characteristics for each prehistoric period. The CS doesn’t achieve any statistical significance for two of the comparison criterium used (i.e., period, archaeological site). Instead, statistically significant differences were recorded between males and females. The greater variability in the shape of M2 compared to M2 was noticed. The M2 model of the Bronze Age is flattened mesiodistal compared to the Chalcolithic one, while differences in M2 morphotypes are associated with the hypocone shape, particularly. ConclusionThis study of dental morphology provides new data that could contribute as evidence of interactions between biological human groups in different regional prehistoric contexts.

3D genome organization links non-coding disease-associated variants to genes.

Genome sequencing has revealed over 300 million genetic variations in human populations. Over 90% of variants are single nucleotide polymorphisms (SNPs), the remainder include short deletions or insertions, and small numbers of structural variants. Hundreds of thousands of these variants have been associated with specific phenotypic traits and diseases through genome wide association studies which link significant differences in variant frequencies with specific phenotypes among large groups of individuals. Only 5% of disease-associated SNPs are located in gene coding sequences, with the potential to disrupt gene expression or alter of the function of encoded proteins. The remaining 95% of disease-associated SNPs are located in non-coding DNA sequences which make up 98% of the genome. The role of non-coding, disease-associated SNPs, many of which are located at considerable distances from any gene, was at first a mystery until the discovery that gene promoters regularly interact with distal regulatory elements to control gene expression. Disease-associated SNPs are enriched at the millions of gene regulatory elements that are dispersed throughout the non-coding sequences of the genome, suggesting they function as gene regulation variants. Assigning specific regulatory elements to the genes they control is not straightforward since they can be millions of base pairs apart. In this review we describe how understanding 3D genome organization can identify specific interactions between gene promoters and distal regulatory elements and how 3D genomics can link disease-associated SNPs to their target genes. Understanding which gene or genes contribute to a specific disease is the first step in designing rational therapeutic interventions.

Development of a Piezoresistive Pressure Sensor Using an in-House Pulsewave Simulator to Ensure Detection of Full Pulse Waveform on Diverse Populations

Flexible and skin mountable wearable health monitoring devices have gained much attention in recent years due to their non-invasive approach to continuous monitoring of weak human physiological signals. In general, ultra-sensitive pressure sensors can be categorized by the operation mechanism into piezoresistive, capacitive, triboelectric, and piezoelectric sensors. Specifically, piezoresistive sensors has drawn much attention because of their fast response, broad detection range, simple structure, and relative simplicity of the signal measuring system. Despite the success of the past efforts in acquiring the full pulse waveform of the human heartbeat, their signal acquisition requires utilization of unwearable measuring equipment. In this study, the central research objective will be to do finite element analysis to optimize the design, and then to fabricate, test and finally verify wearability of the full system (including the signal acquisition portion) on the wrist. A piezoresistive pressure sensor capable of precise monitoring of arterial pulse waveform allows detection of not only the pulse but also possible irregularities in its waveform that can be potentially the harbingers of various medical conditions. Modeling of the sensor’s micro-features showed micro-features with the shape of a pyramid, size of 100 μm, angle of 50-60 degrees and spatial configuration of 1 per 300 μm realizes high sensitivity and signal level (1 mA for pulse waveform detection from the wrist). This helps to eliminate the dependability of the sensor response read-out on complex and unportable measuring devices such as sourcemeters. Furthermore, fabrication of the conductive micro-patterned sensor has been accomplished by the standard micro-fabrication techniques including photolithography and wet etching. Methods such as electrospinning, bipolar exfoliation of graphene and electrostatic spray deposition were used to ensure long term stable conductivity and operation of the device. After the fabrication, this piezoresistive sensor was fully calibrated and characterized by a developed pulse waveform simulator to ensure viability of the system to detect the full pulse waveform from the wrist with various amplitudes of excitation signal (accounting for diverse human population with different pulse strengths). The detailed results will be discussed during the presentation.

Generalized resistance to pruritogen-induced scratching in the C3H/HeJ strain.

Previously the effect of the pruritogens, such as histamine and chloroquine, was tested in 11 inbred mouse strains, and this study aimed to identify resistant and sensitive strains, consistent with the observation that underlies the large variability in human populations. In the present study, we used the low responder C3H/HeJ (C3H) and the more sensitive C57BL/6J (C57) strain to find out if resistance and sensitivity to develop pruritus is restricted to only histamine and chloroquine or extends to other known pruritogens as well. We tested five additional commonly known pruritogens. We established dose-response relationships by injecting four concentrations of the pruritogens in the range of 0.3, 1, 3, and ten-fold in the nuchal fold. Then we assessed the scratching behavior for 30 min after injection with an automated custom-designed device based on the bilateral implantation of mini-magnets in the hind paws and on single cages placed within a magnetic coil. We found that the resistance to pruritogens is a general phenotype of the C3H strain and extends to all pruritogens tested, including not only histamine and chloroquine, but also endothelin, trypsin, 5-HT (serotonin), the short peptide SLIGRL, and Lysophosphatidic acid (LPA). C57 was more sensitive to all pruritogens and, in contrast to C3H, dose-response relationships were evident for some of the pruritogens. In general, comparable peak scratch responses were observed for the 0.3-fold concentrations of the pruritogens in C57 whereas C3H required at least the ten-fold concentration and still displayed only between 5 and 33% of the scratch responses observed in C57 for the respective pruritogen. The general resistance to pruritogens and the low level of scratching behavior found in the C3H strain is an interesting trait and represents a model for the study of the heritability of itch. It is accompanied in C3H with a higher sensitivity in assays of nociception.

Black Joy

When the Stop Your Silence organization began in the spring of 2020, our goal was to create a safe space where Brigham Young University students of color could share their stories of racist discrimination and hardships and find community, healing, and support. Via Instagram, we rapidly received hundreds of stories and began to expand our content and audience not only to people of color but to white members of the Church. We realized there was a need for antiracist education specifically geared toward Latter-day Saints that showed how our doctrines and beliefs not only encourage but exhort us as disciples of Christ to mourn with those who mourn and take a stand against racial injustice.I was initially drawn to Mikenzi Jones's work for how it unapologetically displays femininity. Through vibrant yet soft shades, organic line work, and a vast range of skin tones and body compositions, Jones's artwork reflects the stunning essence of womanhood and all its diversity. Positive, euphoric, non-sexualized artwork for women can be difficult to find. But Jones is able to capture the beauty of women and the wondrous work that can be accomplished when they come together across racial, cultural, and national divides.A common struggle Latter-day Saints of color have expressed to us at Stop Your Silence was a lack of representation. Whether it be in their congregations, in Church leadership, in music or worship styles, these Saints feel disregarded and unheard for a multitude of reasons. However, there was one area in particular regarding representation that came up repeatedly: the overwhelmingly whitewashed depictions of Christ, God, and scriptural figures. The most well-known and highly circulated artistic renderings in the LDS art tradition tend to depict white, hypermasculine men. There was a lack of artwork that featured women from scripture and people of color that didn't fall into the racist “black-skinned” Lamanite caricature. With this in mind, we made it a priority to only highlight art that depicted people of color. Our page is filled with renderings of Black Heavenly Mothers, Indigenous angels, brown-skinned Christs, and more. It is our belief that our Heavenly Parents blessed the world by creating a beautifully diverse human population, and that every child of God deserves to see themselves represented in the divine. To deny someone that connection with God and to force God to fit solely in the square of whiteness is damaging to all of us. It is paramount to our relationship as human beings to see each other and God fully and honestly, to see clearly the stunning medley of divine creation on this earth.The cover art for this issue in particular also highlights something that for me, as a Black woman, is often overlooked in art: joy. Oftentimes Black women are shown and described as strong, confident, independent, and persevering. These are all qualities that many Black women exude and epitomize, but what is missing is their inner happiness and joy. Black women are rarely given the space to simply exist and be joyous, to reside in a space that isn't defined by activism, emotional labor, and work. The Black woman on the cover of this issue effuses a joy and radiance that I hope all Black women, but especially Black Mormon women, can experience as they navigate this world. While they remain confident and strong, I hope they, too, can have joy.

The hospital as a laboratory: Population studies at Tel-Hashomer hospital in Israel (1950s-1960s).

In this article we examine how a leading Israeli hospital gradually became a large biomedical research facility, resembling a huge laboratory. For Chaim Sheba (1908-1971), the founder and first director of Tel-Hashomer Hospital, the massive immigration to Israel in the 1950s was a unique opportunity for research of diverse human populations, especially Jews who had arrived to Israel from Asia and Africa. The paper focuses on the way research and medical practices were integrated and their boundaries blurred, and studies the conditions under which an entire hospital became a research field. Using the case of one of Israel's prominent medical institutes, we explore and expand upon the idea of "the hospital as a laboratory," arguing that, for Sheba, it was not only the hospital but the entire country that functioned as a great research site-a vast laboratory that "had no walls."

Development of a Coherent Model for Radiometric Core Body Temperature Sensing.

This paper examines the utility of a wideband, physics-based model to determine human core body or brain temperature via microwave radiometry. Pennes's bioheat equation is applied to a six-layer human head model to generate the expected layered temperature profile during the development of a fever. The resulting temperature profile is fed into the forward electromagnetic (EM) model to determine the emitted brightness temperature at various points in time. To accurately retrieve physical temperature via radiometry, the utilized model must incorporate population variation statistics and cover a wide frequency band. The effect of human population variation on emitted brightness temperature is studied by varying the relevant thermal and EM parameters, and brightness temperature emissions are simulated from 0.1 MHz to 10 GHz. A Monte Carlo simulation combined with literature-derived statistical distributions for the thermal and EM parameters is performed to analyze population-level variation in resulting brightness temperature. Variation in thermal parameters affects the offset of the resulting brightness temperature signature, while EM parameter variation shifts the key maxima and minima of the signature. The layering of high and low permittivity layers creates these key maxima and minima via wave interference. This study is one of the first to apply a coherent model to and the first to examine the effect of population-representative variable distributions on radiometry for core temperature measurement. These results better inform the development of an on-body radiometer useful for core body temperature measurement across the human population.

Screening For Phenylthiocarbamide Taste Sensitivity Response Status On Apparently Healthy Subjects: A Pilot Study

The dynamics of studying genetic variation in human population using phenylthiocarbamide has contributed immensely in influencing our knowledge of variations and diversity globally. The pilot study aims to screen for the taste sensitivity response status using different concentrations of a stock solution of 0.10% phenylthiocarbamide. 232 subjects were randomly recruited using a drawn questionnaire. 84.9% were tasters while 15.1 % were non-tasters. Of the 133 males, 52.3% were Tasters while 85.7% were non-Tasters. The 99 females, constituted 47.7% Tasters and 14.3% non-tasters. The Chi-Square analysis on gender was significant p-<0.000. The result of the different age range showed a decrease in the population of tasters with increase in age and a reverse among non-tasters. The phenotypic status of the age range of subjects was not significant p> 0.433. The combined allelic frequency of tasters and non - tasters was 0.61 and 0.39. Similarly, the individual allelic frequencies of male and female tasters were 0.52 and 0.78 while male and female non-tasters were 0.48 and 0.22, respectively. The pooled homozygous and heterozygous outcome for males was the same (0.50), but females were 0.66 and 0.34. The homozygous and heterozygous outcome of the combined population was 0.52 and 0.48. The highest cases of tasters were recorded at a threshold of 0.025 and 0.50 with female subjects responding most. The study provides insight to the distribution of the Phenylthiocarbamide phenotype, the heterozygous, homozygous and allelic frequencies of the population, which may serve as an index for directing dietary choice or diagnoses by health care professionals.

Cancer-driving mutations are enriched in genic regions intolerant to germline variation.

Large reference datasets of protein-coding variation in human populations have allowed us to determine which genes and genic subregions are intolerant to germline genetic variation. There is also a growing number of genes implicated in severe Mendelian diseases that overlap with genes implicated in cancer. We hypothesized that cancer-driving mutations might be enriched in genic subregions that are depleted of germline variation relative to somatic variation. We introduce a new metric, OncMTR (oncology missense tolerance ratio), which uses 125,748 exomes in the Genome Aggregation Database (gnomAD) to identify these genic subregions. We demonstrate that OncMTR can significantly predict driver mutations implicated in hematologic malignancies. Divergent OncMTR regions were enriched for cancer-relevant protein domains, and overlaying OncMTR scores on protein structures identified functionally important protein residues. Last, we performed a rare variant, gene-based collapsing analysis on an independent set of 394,694 exomes from the UK Biobank and find that OncMTR markedly improves genetic signals for hematologic malignancies.

Non-linear machine learning models incorporating SNPs and PRS improve polygenic prediction in diverse human populations

Polygenic risk scores (PRS) are commonly used to quantify the inherited susceptibility for a trait, yet they fail to account for non-linear and interaction effects between single nucleotide polymorphisms (SNPs). We address this via a machine learning approach, validated in nine complex phenotypes in a multi-ancestry population. We use an ensemble method of SNP selection followed by gradient boosted trees (XGBoost) to allow for non-linearities and interaction effects. We compare our results to the standard, linear PRS model developed using PRSice, LDpred2, and lassosum2. Combining a PRS as a feature in an XGBoost model results in a relative increase in the percentage variance explained compared to the standard linear PRS model by 22% for height, 27% for HDL cholesterol, 43% for body mass index, 50% for sleep duration, 58% for systolic blood pressure, 64% for total cholesterol, 66% for triglycerides, 77% for LDL cholesterol, and 100% for diastolic blood pressure. Multi-ancestry trained models perform similarly to specific racial/ethnic group trained models and are consistently superior to the standard linear PRS models. This work demonstrates an effective method to account for non-linearities and interaction effects in genetics-based prediction models.

Complex interactions between p.His558Arg and linked variants in the sodium voltage-gated channel alpha subunit 5 (Na V 1.5).

Common genetic polymorphisms may modify the phenotypic outcome when co-occurring with a disease-causing variant, and therefore understanding their modulating role in health and disease is of great importance. The polymorphic p.His558Arg variant of the sodium voltage-gated channel alpha subunit 5 (NaV1.5) encoded by the SCN5A gene is a case in point, as several studies have shown it can modify the clinical phenotype in a number of cardiac diseases. To evaluate the genetic backgrounds associated with this modulating effect, we reanalysed previous electrophysiological findings regarding the p.His558Arg variant and further assessed its patterns of genetic diversity in human populations. The NaV1.5 p.His558Arg variant was found to be in linkage disequilibrium with six other polymorphic variants that previously were also associated with cardiac traits in GWAS analyses. On account of this, incongruent reports that Arg558 allele can compensate, aggravate or have no effect on NaV1.5, likely might have arose due to a role of p.His558Arg depending on the additional linked variants. Altogether, these results indicate a major influence of the epistatic interactions between SCN5A variants, revealing also that phenotypic severity may depend on the polymorphic background associated to each individual genome.

Prediction of infectivity of SARS-CoV-2 virus based on Spike-hACE-2 interaction.

The COVID-19 pandemic caused by SARS-CoV-2 results almost 3 M death worldwide and till continuing in spite of having several vaccine against the virus. One of the main reasons is the mutations occur in the virus to cope with the environment. Detail study of genomics and proteomics level of each components may help to combat the situation. Spike (S) protein that covers the surface of the virus helps in entry by encountering the host receptor Human Angiotensin-Converting Enzyme-2 (hACE-2) with other different roles. In this study, we accomplish our work with the mutations in receptor binding domain (RBD) of Spike (S) protein considering different aspects like the hACE-2 variants in human populations to get an idea about the varying infectivity of different strains for different population. Several other parameters affecting the viral infectivity and in different diseased condition were also studied which may guide to a better insight in developing future therapeutics.

Ancient dental calculus preserves signatures of biofilm succession and interindividual variation independent of dental pathology.

Dental calculus preserves oral microbes, enabling comparative studies of the oral microbiome and health through time. However, small sample sizes and limited dental health metadata have hindered health-focused investigations to date. Here, we investigate the relationship between tobacco pipe smoking and dental calculus microbiomes. Dental calculus from 75 individuals from the 19th century Middenbeemster skeletal collection (Netherlands) were analyzed by metagenomics. Demographic and dental health parameters were systematically recorded, including the presence/number of pipe notches. Comparative data sets from European populations before and after the introduction of tobacco were also analyzed. Calculus species profiles were compared with oral pathology to examine associations between microbiome community, smoking behavior, and oral health status. The Middenbeemster individuals exhibited relatively poor oral health, with a high prevalence of periodontal disease, caries, heavy calculus deposits, and antemortem tooth loss. No associations between pipe notches and dental pathologies, or microbial species composition, were found. Calculus samples before and after the introduction of tobacco showed highly similar species profiles. Observed interindividual microbiome differences were consistent with previously described variation in human populations from the Upper Paleolithic to the present. Dental calculus may not preserve microbial indicators of health and disease status as distinctly as dental plaque.

A Home-Based Approach to Auditory Brainstem Response Measurement: Proof-of-Concept and Practical Guidelines.

Broad-scale neuroscientific investigations of diverse human populations are difficult to implement. This is because the primary neuroimaging methods (magnetic resonance imaging, electroencephalography [EEG]) historically have not been portable, and participants may be unable or unwilling to travel to test sites. Miniaturization of EEG technologies has now opened the door to neuroscientific fieldwork, allowing for easier access to under-represented populations. Recent efforts to conduct auditory neuroscience outside a laboratory setting are reviewed and then an in-home technique for recording auditory brainstem responses (ABRs) and frequency-following responses (FFRs) in a home setting is introduced. As a proof of concept, we have conducted two in-home electrophysiological studies: one in 27 children aged 6 to 16 years (13 with autism spectrum disorder) and another in 12 young adults aged 18 to 27 years, using portable electrophysiological equipment to record ABRs and FFRs to click and speech stimuli, spanning rural and urban and multiple homes and testers. We validate our fieldwork approach by presenting waveforms and data on latencies and signal-to-noise ratio. Our findings demonstrate the feasibility and utility of home-based ABR/FFR techniques, paving the course for larger fieldwork investigations of populations that are difficult to test or recruit. We conclude this tutorial with practical tips and guidelines for recording ABRs and FFRs in the field and discuss possible clinical and research applications of this approach.

Dimension variability of the M2 human molar teeth: comparisons between prehistoric and medieval samples

Teeth are a valuable source of information for studies regarding past human populations in archaeological and forensic contexts. In dental anthropology, the linear measurements of tooth crowns are used for assessing morphological variability and sexual dimorphism in both modern and past human populations. The aim of this research is to evaluate the M2 molar crown variability in archaeological human populations from Prehistory (Chalcolithic and Bronze Age, ~ 5000-1150 BCE) and Middle Ages (13th-17th centuries) discovered in sites from North-Eastern Romania. The objectives of this study emphasize on the diachronic comparison of the M2 molar crown variables between prehistoric and medieval samples (1), and the assessment of sexual dimorphism expression (2). The two crown measurements, mesio-distal (MD) and bucco-lingual (BL) diameters, were performed using ImageJ software on occlusal digital images acquired stereo-microscopically. The crown index (CI), crown area (CA) and the sexual dimorphism index (SDI), along with the two linear measurements, were subjected to univariate and multivariate statistical analysis. Our results show that the variation coefficient (CV) differs for the MD variable in the female upper M2 molars, being higher in the medieval sample than the prehistoric one; also, a higher variability is remarked for the mandibular molar in the medieval sample than in prehistoric one. In females, the MD and CA variables for mandibular M2 molars and the BL and CA for maxillary molars showed significant statistical differences between the medieval and prehistoric mandibular teeth, with higher values for the exemplar from Middle Ages. Similar result was obtained in males, for the CA variable in the upper M2 molars. In our study, the sexual dimorphism manifested at the M2 crown molar was highlighted in the prehistoric sample, though less in the medieval one.

Mutual Exclusion of Methanobrevibacter Species in the Human Gut Microbiota Facilitates Directed Cultivation of a Candidatus Methanobrevibacter Intestini Representative.

ABSTRACTMethanogenic Archaea (methanogens) are a phylogenetically diverse group of microorganisms and are considered to be the most abundant archaeal representatives in the human gut. However, the gut methanogen diversity of human populations in many global regions remains poorly investigated. Here, we report the abundance and diversity of gut methanogenic Archaea in a multi-ethnic cohort of healthy Singaporeans by using a concerted approach of metagenomic sequencing, 16S rRNA gene amplicon sequencing, and quantitative PCR. Our results indicate a mutual exclusion of Methanobrevibacter species, i.e., the highly prevalent Methanobrevibacter smithii and the less prevalent Candidatus Methanobrevibacter intestini in more than 80% of the samples when using an amplicon sequencing-based approach. Leveraging on this finding, we were able to select a fecal sample to isolate a representative strain, TLL-48-HuF1, for Candidatus Methanobrevibacter intestini. The analyzed physiological parameters of M. smithii DSM 861T and strain TLL-48-HuF1 suggest high similarity of the two species. Comparative genome analysis and the mutual exclusion of the Methanobrevibacter species indicate potentially different niche adaptation strategies in the human host, which may support the designation of Candidatus M. intestini as a novel species.IMPORTANCE Methanogens are important hydrogen consumers in the gut and are associated with differing host health. Here, we determine the prevalence and abundance of archaeal species in the guts of a multi-ethnic cohort of healthy Singapore residents. While Methanobrevibacter smithii is the most prevalent and abundant methanogen in the human gut of local subjects, the recently proposed Candidatus Methanobrevibacter intestini is the abundant methanogen in a minority of individuals that harbor them. The observed potential mutual exclusion of M. smithii and Ca. M. intestini provides further support to the proposal that the two physiologically similar strains may belong to different Methanobrevibacter species.

Research problems in Biological Anthropology: Flaws in sampling and in methods of results analysis

Anthropology has as ambition the study of the whole of humanity. It includes several specialties and sub-specialties that, despite their differences, offer an overall perspective that requires a holistic research approach. In Biological Anthropology, one of its specialties, anthropologists study biological variations in contemporary human populations in order to reveal their characteristics and their genetic relationships and to try, on the basis of analysis of these variations and those revealed in human fossils, to trace the evolution of human lineage through time. In this report, I provide an overview of some research major problems met in biological anthropology. I evoke especially the problems of the use of uncertain results analysis methods and those of incorrect samplings. In addition to the presentation of these problems and their consequences I present alternatives and suitable solutions. I also explain how some classic considerations resulting from some of these problems could hinder scientific progress in the topic in question. Hence, I believe it is time to avoid these problems, to eradicate the resulting considerations and to follow the most realistic research tracks.