Profiling genetically driven alternative splicing across the Indonesian archipelago.

One of the regulatory mechanisms influencing the functional capacity of genes is alternative splicing (AS). Previous studies exploring the splicing landscape of human tissues have shown that AS has contributed to human biology, especially in disease progression and the immune response. Nonetheless, this phenomenon remains poorly characterized across human populations, and it is unclear how genetic and environmental variation contribute to AS. Here, we examine a set of 115 Indonesian samples from three traditional island populations spanning the genetic ancestry cline that characterizes Island Southeast Asia. We conduct a global AS analysis between islands to ascertain the degree of functionally significant AS events and their consequences. Using an event-based statistical model, we detected over 1,500 significant differential AS events across all comparisons. Additionally, we identify over 6,000 genetic variants associated with changes in splicing (splicing quantitative trait loci [sQTLs]), some of which are driven by Papuan-like genetic ancestry, and only show partial overlap with other publicly available sQTL datasets derived from other populations. Computational predictions of RNA binding activity reveal that a fraction of these sQTLs directly modulate the binding propensity of proteins involved in the splicing regulation of immune genes. Overall, these results contribute toward elucidating the role of genetic variation in shaping gene regulation in one of the most diverse regions in the world.

Everyday language input and production in 1,001 children from six continents.

Language is a universal human ability, acquired readily by young children, who otherwise struggle with many basics of survival. And yet, language ability is variable across individuals. Naturalistic and experimental observations suggest that children's linguistic skills vary with factors like socioeconomic status and children's gender. But which factors really influence children's day-to-day language use? Here, we leverage speech technology in a big-data approach to report on a unique cross-cultural and diverse data set: >2,500 d-long, child-centered audio-recordings of 1,001 2- to 48-mo-olds from 12 countries spanning six continents across urban, farmer-forager, and subsistence-farming contexts. As expected, age and language-relevant clinical risks and diagnoses predicted how much speech (and speech-like vocalization) children produced. Critically, so too did adult talk in children's environments: Children who heard more talk from adults produced more speech. In contrast to previous conclusions based on more limited sampling methods and a different set of language proxies, socioeconomic status (operationalized as maternal education) was not significantly associated with children's productions over the first 4 y of life, and neither were gender or multilingualism. These findings from large-scale naturalistic data advance our understanding of which factors are robust predictors of variability in the speech behaviors of young learners in a wide range of everyday contexts.

Biogeographic Perspectives on Human Genetic Diversification.

Modern humans originated in Africa 300,000 yr ago, and before leaving their continent of origin, they underwent a process of intense diversification involving complex demographic dynamics. Upon exiting Africa, different populations emerged on the four other inhabited continents, shaped by the interplay of various evolutionary processes, such as migrations, founder effects, and natural selection. Within each region, continental populations, in turn, diversified and evolved almost independently for millennia. As a backdrop to this diversification, introgressions from archaic species contributed to establishing different patterns of genetic diversity in different geographic regions, reshaping our understanding of our species' variability. With the increasing availability of genomic data, it has become possible to delineate the subcontinental human population structure precisely. However, the bias toward the genomic research focused on populations from the global North has limited our understanding of the real diversity of our species and the processes and events that guided different human groups throughout their evolutionary history. This perspective is part of a series of articles celebrating 40 yr since our journal, Molecular Biology and Evolution, was founded (Russo et al. 2024). The perspective is accompanied by virtual issues, a selection of papers on human diversification published by Genome Biology and Evolution and Molecular Biology and Evolution.

Social ecological predictors and correlates of Latinos' IPV behaviors: A systematic review and critique of the research literature.

The current paper utilizes an ecological level of analysis framework to review and critique the literature surrounding predictors, correlates, and antecedents of Latinos' intimate partner violence (IPV) behaviors. More specifically, the ecological levels of analysis framework was employed to demonstrate how Latino males' IPV perpetration is being understood and studied. A total of n = 34 peer-reviewed articles were reviewed and critiqued. Findings indicated that most IPV research is being conducted at and comprehended from the individual (n = 33; 97%) and microsystem/small group (n = 24; 71%) levels of analysis, while linkages to organizational, locality, and institutional levels of analysis are largely neglected. Researchers and interventionists appear to view Latinos' IPV behaviors through deficit models, employ decontextualized and homogenized representations of the population, and neglect higher ecological levels of analysis. These three shortcomings in IPV research as it pertains to Latino populations must be addressed in future research studies if investigators desire to end the stigmatization and demonization of Latinos as a cultural and people group, and to maximize battering intervention effectiveness and efficiency for men of Latino origin.

Reassessment of the human mandible from Banyoles (Girona, Spain).

Since the discovery of a human mandible in 1887 near the present-day city of Banyoles, northeastern Spain, researchers have generally emphasized its archaic features, including the lack of chin structures, and suggested affinities with the Neandertals or European Middle Pleistocene (Chibanian) specimens. Uranium-series and electron spin resonance dating suggest the mandible dates to the Late Pleistocene (Tarantian), approximately ca. 45-66 ka. In this study, we reassessed the taxonomic affinities of the Banyoles mandible by comparing it to samples of Middle Pleistocene fossils from Africa and Europe, Neandertals, Early and Upper Paleolithic modern humans, and recent modern humans. We evaluated the frequencies and expressions of morphological features and performed a three-dimensional geometric morphometric analysis on a virtual reconstruction of Banyoles to capture overall mandibular shape. Our results revealed no derived Neandertal morphological features in Banyoles. While a principal component analysis based on Euclidean distances from the first two principal components clearly grouped Banyoles with both fossil and recent Homo sapiens individuals, an analysis of the Procrustes residuals demonstrated that Banyoles did not fit into any of the comparative groups. The lack of Neandertal features in Banyoles is surprising considering its Late Pleistocene age. A consideration of the Middle Pleistocene fossil record in Europe and southwest Asia suggests that Banyoles is unlikely to represent a late-surviving Middle Pleistocene population. The lack of chin structures also complicates an assignment to H. sapiens, although early fossil H. sapiens do show somewhat variable development of the chin structures. Thus, Banyoles represents a non-Neandertal Late Pleistocene European individual and highlights the continuing signal of diversity in the hominin fossil record. The present situation makes Banyoles a prime candidate for ancient DNA or proteomic analyses, which may shed additional light on its taxonomic affinities.

A systematic review suggests marked differences in the prevalence of infant-directed vocalization across groups of populations.

Anthropological reports have long suggested that speaking to young children is very infrequent in certain populations (notably farming ones), which is in line with scattered quantitative studies. A systematic review was undertaken to use available literature in order to estimate the extent of population variation. Database searches, expert lists, and citation searches led to the discovery of 29 reports on the frequency of vocalizations directed to infants aged 24 months or younger, based on systematic observations of spontaneous activity in the infant's natural environment lasting at least 30 min in length. Together, these studies provide evidence on 1314 infants growing up in a range of communities (urban, foraging, farming). For populations located outside of North America, the frequency with which vocalization was directed to urban infants was much higher than that for rural infants (including both foraging and farming, medians = 12.6 vs. 3.6% of observations contained infant-directed vocalization behaviors). We benchmarked this effect against socio-economic status (SES) variation in the United States, which was much smaller. Infants in high SES American homes were spoken to only slightly more frequently than those in low SES homes (medians = 16.4 vs. 15.1% of observations contained infant-directed vocalization behaviors). Although published research represents a biased sample of the world's populations, these results invite further cross-population research to understand the causes and effects of such considerable population group differences.

A human diversity analysis of culture and gender in Asian American men's intimate partner violence perpetration.

This integrative literature review aims to fill the gap in our understanding of the cultural and gendered predictors of intimate partner violence (IPV) perpetration by Asian American men. A comprehensive search using PsycINFO returned N = 24 peer-reviewed journal articles that examine Asian American men's IPV perpetration and patriarchal gender role norms and that met inclusion criteria. Patriarchal gender role norms consistently predicted IPV perpetration. However, the associations between acculturation/enculturation and IPV perpetration were less clear. Greater enculturation (Asian cultural identification) was associated with more patriarchal gender role norms while greater acculturation (mainstream US cultural identification) was associated with more masculine gender role strain. Additionally, violence in the family of origin consistently predicted later IPV perpetration as an adult. Results suggest that integrating multiple dimensions of human diversity (e.g., culture, gender, and power) in intersectional models may best explain Asian American men's IPV perpetration.

Genetic admixture in Brazil.

We review studies from our laboratories using different molecular tools to characterize the Amerindian, European and African ancestry of Brazilians. Initially we used uniparental DNA markers to investigate the contribution of distinct Y chromosome and mitochondrial DNA lineages to present-day populations. High levels of genetic admixture and strong directional mating between European males and Amerindian and African females were unraveled. We next analyzed different types of biparental autosomal polymorphisms. Especially useful was a set of 40 insertion-deletion polymorphisms (indels) that when studied worldwide proved exquisitely sensitive in discriminating between Amerindians, Europeans and Sub-Saharan Africans. When applied to the study of Brazilians these markers confirmed extensive genomic admixture. We then studied ancestry differences in different regions by statistically controlling them to eliminate color considerations. The European ancestry was predominant in all regions studied, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of 6 million Europeans to Brazil in the 19th and 20th centuries is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. Brazilians should be assessed individually, as 210 million human beings, and not as members of specific regions or color groups.

Discovery of copy number variants by multiplex amplifiable probe hybridization (MAPH) in candidate pigmentation genes.

BACKGROUND: Copy Number Variants (CNVs) contribute to a large fraction of genetic diversity and some of them have been reported to offer an evolutionary advantage. AIM: To identify CNVs in pigmentary loci that could contribute to human skin pigmentation diversity. SUBJECTS AND METHODS: This study assessed the existence of CNVs in every exon of candidate genes: TYR, TYRP1, DCT, MC1R and SLC24A5, using the Multiplex Amplifiable Probe Hybridization technique (MAPH). This study analysed a total of 99 DNA samples of unrelated individuals from different populations. Validation and further analysis in a larger Spanish sample were performed by RT-qPCR. RESULTS: Five CNVs were identified by MAPH: DCT exons 4 and 8, TYR exon 1 and SLC24A5 exons 1 and 4. Real-time quantitative PCR (RT-qPCR) confirmed the CNV in exon 1 of SLC24A5. This study further analysed the 5' promoter region of SLC24A5 and found another CNV in this region. However, no association was found between the CNV and the degree of pigmentation. CONCLUSION: Although the functional role of these structural variants in pigmentation should be the subject of future work, the results emphasize the need to consider all classes of variation (both SNPs and CNVs) when exploring the genetics of skin pigmentation.

Sex-biased gene regulation varies across human populations as a result of adaptive evolution.

OBJECTIVES: Studies of human sexual dimorphism and gender disparities in health focus on ostensibly universal molecular sex differences, such as sex chromosomes and circulating hormone levels, while ignoring the extraordinary diversity in biology, behavior, and culture acquired by different human populations over their unique evolutionary histories. MATERIALS AND METHODS: Using RNA-Seq data and whole genome sequences from 1000G and HGDP, we investigate variation in sex-biased gene expression across 11 human populations and test whether population-level variation in sex-biased expression may have resulted from adaptive evolution in regions containing sex-specific regulatory variants. RESULTS: We find that sex-biased gene expression in humans is highly variable, mostly population-specific, and demonstrates between population reversals. Expression quantitative trait locus mapping reveals sex-specific regulatory regions with evidence of recent positive natural selection, suggesting that variation in sex-biased expression may have evolved as an adaptive response to ancestral environments experienced by human populations. DISCUSSION: These results indicate that sex-biased gene expression is more flexible than previously thought and is not generally shared among human populations. Instead, molecular phenotypes associated with sex depend on complex interactions between population-specific molecular evolution and physiological responses to contemporary socioecologies.

Early onset of enamel formation in Baka pygmy's deciduous canines.

OBJECTIVE: Our aim was to evaluate by enamel microstructure analysis two hypotheses that would explain the early dental eruption in the Bakaparticularity, a shorter crown formation time and/or earlier onset of crown formation. DESIGN: Deciduous canines corresponds to the best teeth to perform the analysis of enamel microstructure. Longitudinal ground sections of 21 deciduous canines from 12 individuals were studied with transmitted light microscopy. Cross-striations, striaes of Retzius (SR) and the neonatal line (NNL) enable to establish the prenatal crown formation time (preCFT), the postnatal crown formation time (postCFT), the crown formation time (CFT) as well as the daily secretion rate (DSR) and the enamel extension rate (EER) and their variation along crown formation. RESULTS: The DSR and the EER in the Baka are similar than in other populations with an average DSR of 3.26 µm and EER of 18.18 µm. The preCFT was 154 days, the postCFT 265 days and CFT 419 days. Comparison with other population does not show difference in CFT. However, the preCFT and the postCFT differ, the first is higher and the second lower in the Baka than in other populations. Furthermore, the number of prenatal areas of enamel was greater in the Baka. CONCLUSION: Our analysis suggests that the Baka does not distinguish by a different CFT but the onset of crown formation is earlier than in other groups. Therefore, the early dental eruption in the Baka results from an earlier onset of crown formation.

The genetic and evolutionary basis of gene expression variation in East Africans.

BACKGROUND: Mapping of quantitative trait loci (QTL) associated with molecular phenotypes is a powerful approach for identifying the genes and molecular mechanisms underlying human traits and diseases, though most studies have focused on individuals of European descent. While important progress has been made to study a greater diversity of human populations, many groups remain unstudied, particularly among indigenous populations within Africa. To better understand the genetics of gene regulation in East Africans, we perform expression and splicing QTL mapping in whole blood from a cohort of 162 diverse Africans from Ethiopia and Tanzania. We assess replication of these QTLs in cohorts of predominantly European ancestry and identify candidate genes under selection in human populations. RESULTS: We find the gene regulatory architecture of African and non-African populations is broadly shared, though there is a considerable amount of variation at individual loci across populations. Comparing our analyses to an equivalently sized cohort of European Americans, we find that QTL mapping in Africans improves the detection of expression QTLs and fine-mapping of causal variation. Integrating our QTL scans with signatures of natural selection, we find several genes related to immunity and metabolism that are highly differentiated between Africans and non-Africans, as well as a gene associated with pigmentation. CONCLUSION: Extending QTL mapping studies beyond European ancestry, particularly to diverse indigenous populations, is vital for a complete understanding of the genetic architecture of human traits and can reveal novel functional variation underlying human traits and disease.

The apportionment of citations: a scientometric analysis of Lewontin 1972.

'The apportionment of human diversity' (1972) is the most highly cited research article published by geneticist Richard Lewontin in his career. This study's primary result-that most genetic diversity in humans can be accounted for by within-population differences, not between-population differences-along with Lewontin's outspoken, politically charged interpretations thereof, has become foundational to the scientific and cultural discourse pertaining to human genetic variation. The article has an unusual bibliometric trajectory in that it is much more salient in the bibliographic record today compared to the first 20 years after its publication. Here, we highlight four factors that may have played a role in shaping the paper's fame: (i) citations in influential publications across several disciplines; (ii) Lewontin's own popular books and media appearances; (iii) the renaissance of population genetics research of the early 1990s; and (iv) the serendipitous collision of scientific progress, influential books and papers, and heated controversies around the year 1994. We conclude with an analysis of Twitter data to characterize the communities and conversations that continue to keep this study at the centre of discussions about race and genetics, prompting new challenges for scientists who have inherited Lewontin's legacy. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.

Shaping birth: variation in the birth canal and the importance of inclusive obstetric care.

Regional variation in pelvic morphology and childbirth has long occurred alongside traditional labour support and an understanding of possible normal courses of childbirth for each population. The process of migration and globalization has broken down these links, while a European model of 'normal' labour has become widespread. The description of 'normal' childbirth provided within obstetrics and midwifery textbooks, in fact, is modelled on a specific pelvic morphology that is common in European women. There is mounting evidence, however, that this model is not representative of women's diversity, especially for women of non-white ethnicities. The human birth canal is very variable in shape, both within and among human populations, and differences in pelvic shapes have been associated with differences in the mechanism of labour. Normalizing a white-centred model of female anatomy and of childbirth can disadvantage women of non-European ancestry. Because they are less likely to fit within this model, pelvic shape and labour pattern in non-white women are more likely to be considered 'abnormal', potentially leading to increased rates of labour intervention. To ensure that maternal care is inclusive and as safe as possible for all women, obstetric and midwifery training need to incorporate women's diversity. This article is part of the theme issue 'Multidisciplinary perspectives on social support and maternal-child health'.

Discovery of novel DNA methylation biomarkers for non-invasive sporadic breast cancer detection in the Latino population.

Human diversity is one of the main pitfalls in the development of robust worldwide biomarkers in oncology. Epigenetic variability across human populations is associated with different genetic backgrounds, as well as variable lifestyles and environmental exposures, each of which should be investigated. To identify potential non-invasive biomarkers of sporadic breast cancer in the Uruguayan population, we studied genome-wide DNA methylation using Illumina methylation arrays in leukocytes of 22 women with sporadic breast cancer and 10 healthy women in a case-control study. We described a panel of 38 differentially methylated CpG positions that was able to cluster breast cancer patients (BCP) and controls, and that also recapitulated methylation differences in 12 primary breast tumors and their matched normal breast tissue. Moving forward, we simplified the detection method to improve its applicability in a clinical setting and used an independent well-characterized cohort of 80 leukocyte DNA samples from BCP and 80 healthy controls to validate methylation results at specific cancer-related genes. Our investigations identified methylation at CYFIP1 as a novel epigenetic biomarker candidate for sporadic breast cancer in the Uruguayan population. These results provide a proof-of-concept for the design of larger studies aimed at validating biomarker panels for the Latin American population.

The Human Wallace Line: Racial Science and Political Afterlife.

This paper examines racial science and its political uses in Southeast Asia. It follows several anthropologists who travelled to east Nusa Tenggara (the Timor Archipelago, including the islands of Timor, Flores and Sumba), where Alfred Russel Wallace had drawn a dividing line between the races of the east and the west of the archipelago. These medically trained anthropologists aimed to find out if the Wallace Line could be more precisely defined with measurements of the human body. The paper shows how anthropologists failed to find definite markers to quantify the difference between Malay and Papuan/Melanesian. This, however, did not diminish the conceptual power of the Wallace Line, as the idea of a boundary between Malays and Papuans was taken up in the political arena during the West New Guinea dispute and was employed as a political tool by all parties involved. It shows how colonial and racial concepts can be appropriated by local actors and dismissed or emphasised depending on political perspectives.

PGG.SNV: understanding the evolutionary and medical implications of human single nucleotide variations in diverse populations.

Despite the tremendous growth of the DNA sequencing data in the last decade, our understanding of the human genome is still in its infancy. To understand the implications of genetic variants in the light of population genetics and molecular evolution, we developed a database, PGG.SNV ( https://www.pggsnv.org ), which gives much higher weight to previously under-investigated indigenous populations in Asia. PGG.SNV archives 265 million SNVs across 220,147 present-day genomes and 1018 ancient genomes, including 1009 newly sequenced genomes, representing 977 global populations. Moreover, estimation of population genetic diversity and evolutionary parameters is available in PGG.SNV, a unique feature compared with other databases.

The Preference for Pointing With the Hand Is Not Universal.

Pointing is a cornerstone of human communication, but does it take the same form in all cultures? Manual pointing with the index finger appears to be used universally, and it is often assumed to be universally preferred over other forms. Non-manual pointing with the head and face has also been widely attested, but it is usually considered of marginal significance, both empirically and theoretically. Here, we challenge this assumed marginality. Using a novel communication task, we investigated pointing preferences in the Yupno of Papua New Guinea and in U.S. undergraduates. Speakers in both groups pointed at similar rates, but form preferences differed starkly: The Yupno participants used non-manual pointing (nose- and head-pointing) numerically more often than manual pointing, whereas the U.S. participants stuck unwaveringly to index-finger pointing. The findings raise questions about why groups differ in their pointing preferences and, more broadly, about why humans communicate in the ways they do.

The Genetic Structure of Human Populations Studied Through Short Insertion-Deletion Polymorphisms.

In a landmark study Rosenberg et al. (2002) analyzed human genome diversity with 377 microsatellites in the HGDP-CEPH Genome Diversity Panel and reported that the populations were structured into five geographical regions: America, Sub-Saharan Africa, East Asia, Oceania and a cluster composed of Europe, the Middle East and Central Asia. They also observed that the within-population component accounted for 93-95%, and that the among-regions portion was only 3.6%, of the total genetic variance. We have also studied the HGDP-CEPH Diversity Panel (1064 individuals from 52 populations) with a set of 40 biallelic slow-evolving short insertion-deletion polymorphisms (indels). We confirmed the partition of worldwide diversity into five genetic clusters that correspond to major geographic regions. Using the indels we have also disclosed an among-regions component of genetic variance considerably larger (12.1%) than had been estimated using microsatellites. Our study demonstrates that a set of 40 well-chosen biallelic markers is sufficient for the characterization of human population structure at the global level.