High-altitude adaptation in Andean populations has traditionally been studied through the lens of genetic variation, with limited exploration of epigenetic mechanisms such as DNA methylation. Here, we present the first whole-methylome data comparing Indigenous populations residing in high-altitude regions of the Ecuadorian Andes to those in low-altitude Peruvian Amazon regions bordering the Andes. By leveraging whole-methylome sequencing rather than methylation arrays, we achieved an unprecedented resolution of epigenetic variation, revealing novel insights into altitude-associated adaptations. We identified significant differentially methylated regions in genes involved in hypoxia response and skin pigmentation that differ from patterns previously observed in high-altitude Tibetan individuals [Lin et al. (Genome-wide DNA methylation landscape of four Chinese populations and epigenetic variation linked to Tibetan high-altitude adaptation. Science China Life Sciences 2023;66:2354–69. https://doi.org/10.1007/s11427-022-2284-8.)]. Our findings highlight the influence that altitude-specific environmental pressures, such as hypoxia and ultraviolet radiation, can have on the epigenetic landscapes observed between human populations. Importantly, we uncovered unique regulatory methylation signatures in the hypoxia response pathways of Andean populations, underscoring a distinct epigenetic trajectory compared to other high-altitude groups. This study represents a step forward in understanding Indigenous American genomic plasticity and demonstrates the value of whole-methylome data over methylation arrays in capturing the complex interplay between epigenetics and the environment. These results support a new approach to studying altitude plasticity and underscore the critical role of epigenetics in shaping population-specific cellular responses in Indigenous communities.

As skin color measurement shifts from subjective classification to quantitative assessment, the assumption that objective measures are unbiased requires scrutiny. We provide a physics-informed framework for interpreting visible-range skin measurements, clarifying terminology, describing light-chromophore interactions, and surveying tools and output metrics. The physics of light-tissue interaction constrains what any visible-range observation can reveal: melanin and hemoglobin absorb across overlapping wavelengths, and as melanin increases, hemoglobin’s signature is masked. By analyzing over 15,000 spectra from the International Skin Spectra Archive, we demonstrate that this attenuation is systematic and most severe in the darkest skin, where data are scarcest. These limits arise from the physical properties of skin’s biological constituents and consequently apply to any sensor operating in the visible range. We conclude with guidance on analytical methods, sampling strategies, and extended wavelengths to improve measurement validity across the full range of human skin pigmentation. Graphical Objective skin measurements are not inherently unbiased: melanin’s broadband absorption progressively masks hemoglobin’s spectral signature, reducing the sensitivity of visible-range erythema detection in darker skin. Summary Points: Visible-range skin reflectance measurements capture real optical information but do not directly measure chromophore concentrations; interpreting these signals requires understanding light-tissue interactions. Melanin and hemoglobin absorb at overlapping wavelengths, creating optical entanglement that limits the separability of pigmentation and erythema signals from reflectance data. Hemoglobin spectral signatures are systematically attenuated as melanin increases, reducing the sensitivity of erythema detection in darker skin. This represents objective bias arising from physics, not subjective bias in assessment. Derivative analysis of full reflectance spectra can reveal hemoglobin-related structure that persists in darker skin even when standard indices show no signal. Melanin index distributions should be reported to assess sample representativeness, as demographic diversity does not guarantee adequate coverage of the pigmentation range relevant to optical measurement. Limitations: Spectral overlap between melanin and hemoglobin is a physical property of these chromophores; no visible-range instrument or algorithm can fully overcome this constraint. These optical limits apply to any visible-range sensor, including spectrophotometers, clinical photography, and AI systems trained on photographic data. Existing datasets remain sparse at the high end of the melanin index distribution, limiting validation of measurement approaches in the darkest skin.

Forensic DNA databases in the United States have expanded substantially over the past two decades. However, comprehensive, harmonised data describing database structure and composition remain limited. This dataset series documents forensic DNA infrastructure across national and state levels from 2001 to 2025. It includes a reconstructed time series of monthly National DNA Index System (NDIS) statistics from FBI archives, capturing counts of offender, arrestee, and forensic profiles, participating laboratory totals, and investigations aided. A complementary dataset compiles publicly available state-level statistics and policy metadata on arrestee collection laws, familial search practices, and DNA collection statutes across all 50 states. A third dataset provides standardised demographic and annual collection data obtained through previously published public records requests, including sex and racial composition where reported. Together, these resources provide a foundation for studying the historical development of forensic DNA systems in the U.S., enabling longitudinal and cross-sectional analyses of database growth, policy variation, and reporting practices across jurisdictions.

Pigmentation and hair morphology are both among the earliest visible traits studied in the context of human heredity and genetics. Over the past 100+ years, both traits have been defined in various ways and their genetic underpinnings have been studied across major methodological approaches in the field to varying degrees of success. Here we review what can be learned from the divergent trajectories of genetic research on these two traits, particularly about how phenotypic definitions shape connections between genetic findings, biological mechanisms, and measured variation. We consider how a new era of functional genomics may integrate these bodies of knowledge, and to move forward our understanding of complex traits, for which pigmentation and hair morphology provide two illustrative models.

The demographic history of pre-Columbian South American populations remains poorly understood, particularly along the Pacific coast where ancient genomic data are scarce. Here, we present the first whole genomes from ancient individuals buried at Salango, Ecuador, spanning ∼2,300 to ∼740 years before present and representing 3 distinct cultural phases. Despite major environmental disruption following the Pululahua volcanic eruption and substantial sociopolitical change, these individuals exhibit remarkable genetic continuity across nearly 2 millennia. Population genetic analyses consistently support long-term continuity at Salango, while demographic modeling suggests that the Ecuadorian coastal lineage diverged from other Southern Native American (SNA) lineages approximately 9,800 years ago (95% CI: 9.6–10.1 ka). Together, these findings are consistent with coastal Ecuador representing a long-standing component of early South American population structure while maintaining connections with neighboring Andean populations through time. In addition, we recovered authentic Mycobacterium tuberculosis complex (MTBC) DNA from an infant dated to ∼2,300 BP with skeletal lesions consistent with tuberculosis, providing molecular evidence for one of the earliest documented cases of MTBC infection in pre-contact South America. Although the moderate pathogen genome coverage precludes detailed phylogenetic interpretation, the combined osteological and molecular evidence expands the record of tuberculosis in ancient South America. Overall, our study provides the first ancient genomic data from Ecuador, establishing an important geographic reference for investigating the demographic and biological history of the Pacific coast of South America.