Ancient DNA has revolutionized the study of extinct and extant organisms that lived up to 2 million years ago, enabling the reconstruction of genomes from multiple extinct species, as well as the ecosystems where they once thrived. However, current DNA sequencing techniques alone cannot directly provide insights into tissue identity, gene expression dynamics, or transcriptional regulation, as these are encoded in the RNA fraction. Here, we report transcriptional profiles from 10 Late Pleistocene woolly mammoths. One of these, dated to be ∼39,000 years old, yielded sufficient detail to recover tissue-specific regulatory mechanisms and biological functions essential for skeletal muscle metabolism, representing the oldest ancient RNA sequences recorded to date. We showcase the potential to study ancient RNA molecules beyond preconceived limitations, providing an analytical framework for validating and decoding preserved transcriptomes through time. With our findings, we anticipate the emergence of integrative paleo-studies combining genomics, proteomics, and transcriptomics.

Objective: In Mexico, two-thirds of the adult population are overweight and almost a quarter are affected by obesity. These high obesity rates are primarily attributed to low-nutrient, high-calorie diets, reduced physical activity, and to a certain extent, genetic factors. Most genetic variants for obesity risk have been identified through studies based predominantly on European populations. This study examines the roles of subcontinental ancestry, genetic polymorphisms, and socio-environmental factors in anthropometric measures within an admixed Mexican population.

Methods: We analyzed a sample of 1195 adult volunteers from the CANDELA consortium. Regression models were used to assess the influence of subcontinental Native American ancestries, socioeconomic level (education and SES), and genetic background on body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Polygenic risk scores (PRS) were constructed for each index using established alleles.

Results: An increase in obesity indices was significantly associated with a higher proportion of Native American ancestry, particularly waist-to-hip ratio. Polygenic risk scores were significantly associated with all indices, with BMI showing the highest risk. The effect of obesity scores was not influenced by ancestry on any of the evaluated indices, although the average frequency of risk alleles was slightly inversely correlated with higher Native American ancestry content.

Conclusions: This study highlights the challenges of assessing genetic predisposition to complex disease in admixed populations, where numerous factors contribute to observed differences, emphasizing the need to consider regional genetic diversity in obesity research.

Using temporarily spaced high-coverage ancient genomes, we can assess population decline prior to extinction. However, finding suitable ancient remains for recovering this type of data is challenging. Here, we sequenced a high-coverage genome from muscle tissue of a 14,400-year-old woolly rhinoceros (Coelodonta antiquitatis)—a cold-adapted herbivore that went extinct ∼14,000-years ago—found inside a permafrost-preserved wolf's stomach. We compared genome-wide diversity, inbreeding, genetic load, and population size changes in this sample with two other Late Pleistocene Siberian woolly rhinoceros. We found no evidence of population size decline, nor any genomic erosion, shortly prior to the species' demise. Given the few long homozygous segments, typically indicative of recent inbreeding, we infer a stable population size only a few centuries before extinction. Thus, the woolly rhinoceros' extinction likely happened rapidly, during the Bølling–Allerød interstadial. This study demonstrates the ability to recover high-quality DNA from unlikely sources to elucidate species' extinction dynamics.

The genomic study of specimens dating to the Early and Middle Pleistocene (EP and MP), a period spanning from 2.6 million years ago (Ma) to 126 thousand years ago (ka), has the potential to elucidate the evolutionary processes that shaped present-day biodiversity. Obtaining genomic data from this period is challenging, but mitochondrial DNA, given its higher abundance compared to nuclear DNA, could play an important role to understand evolutionary processes at this time scale. In this study, we report 34 new mitogenomes, including two EP and nine MP mammoth (Mammuthus spp.) specimens from Siberia and North America and analyze them jointly with >200 publicly available mitogenomes to reconstruct a transect of mammoth mitogenome diversity throughout the last million years. We find that our EP mitogenomes fall outside the diversity of all Late Pleistocene (LP) mammoths, while those derived from MP mammoths are basal to LP mammoth Clades 2 and 3, supporting an ancient Siberian origin of these lineages. In contrast, the geographical origin of Clade 1 remains unresolved. With these new deep-Time mitogenomes, we observe diversification events across all clades that appear consistent with previously hypothesized MP and LP demographic changes. Furthermore, we improve upon an existing methodology for molecular clock dating of specimens >50 ka, demonstrating that specimens need to be individually dated to avoid biases in their age estimates. Both the molecular and analytical improvements presented here highlight the importance of deep-Time genomic data to discover long-lost genetic diversity, enabling better assessments of evolutionary histories.

Ancient genomic studies have extensively explored human-microbial interactions, yet research on non-human animals remains limited. In this study, we analyzed ancient microbial DNA from 483 mammoth remains spanning over 1 million years, including 440 newly sequenced and unpublished samples from a 1.1-million-year-old steppe mammoth. Using metagenomic screening, contaminant filtering, damage pattern analysis, and phylogenetic inference, we identified 310 microbes associated with different mammoth tissues. While most microbes were environmental or post-mortem colonizers, we recovered genomic evidence of six host-associated microbial clades spanning Actinobacillus, Pasteurella, Streptococcus, and Erysipelothrix. Some of these clades contained putative virulence factors, including a Pasteurella-related bacterium that had previously been linked to the deaths of African elephants. Notably, we reconstructed partial genomes of Erysipelothrix from the oldest mammoth sample, representing the oldest authenticated host-associated microbial DNA to date. This work demonstrates the potential of obtaining ancient animal microbiomes, which can inform further paleoecological and evolutionary research.

Paleogenomic studies suggest that Mammuthus columbi derives from an ancient hybridization between Mammuthus primigenius and Mammuthus trogontherii. Although its habitat spanned from North to central America, available genetic data are limited to temperate regions, leaving gaps in knowledge of the species’ demographic history on the continent. In this study, we generated 61 capture-enriched M. columbi mitogenomes from the basin of Mexico, located in central Mexico. Our analysis reveals that these mitogenomes belong to a mitochondrial lineage distinct from that of other North American mammoth mitogenomes. these divergent mitogenomes suggest a deep population structure in their ancestors and challenge prior assumptions based on geographically restricted samples. Our findings underscore the importance of wider spatial sampling to reconstruct mammoths’ evolutionary history and demonstrate the feasibility of studying megafauna from tropical latitudes.

Climate changes profoundly impact species distributions and can drastically alter dynamics between formerly isolated taxa. The evolution of mammoths within North America was characterized by repeated cycles of dispersal and putative gene flow between woolly and Columbian mammoths. However, as genome-wide studies on mammoths have predominantly focused on Siberia, the consequences of these North American range shifts remain unclear. Here, we generated genome-wide and morphological data for two Late Pleistocene mammoth molars from British Columbia, Canada (BC), and jointly analysed these with previously published data. Our genome-wide analysis (n = 16) revealed gene flow between woolly and Columbian mammoths that would have gone undiscovered based on morphological (n = 48) and mitochondrial analysis (n = 124) alone. Consistent with their hybrid nature, our analyses suggest that these two BC mammoths had elevated genomic diversity. Our results highlight the importance of combining data types to reconstruct past evolutionary events. These findings demonstrate how the geographical range expansion of woolly mammoths resulted in long-term hybridization with local Columbian mammoths and enhance our understanding of the genomic and morphological consequences of climate-mediated dispersal.

Bovines have a complex yet poorly understood evolutionary history that is characterized by admixture and diversity loss during the Late Pleistocene. Unraveling this history is challenging in part because deep-time and geographically widespread genetic data are currently limited. In mid-latitude Asia, Denisova Cave, located in the Altai, Siberia, and nearby paleontological sites have yielded a large collection of remains spanning the Middle to Late Pleistocene, many of which are identifiable as bovines via morphology or paleoproteomics. In this study, we screened these bovine bones for ancient DNA and generated mitogenomes, to refine knowledge of Pleistocene bovine diversity in the region. We found that bovines carrying a yak-like mitogenome were common residents of the Altai mountains, along with bison belonging to the clade X mitochondrial lineage and, more rarely, aurochs. The yak-like mitochondrial lineage identified in this study represents a previously unknown lineage sister to present-day yak mitogenome diversity. This yak-like mitochondrial lineage, termed yak X, was identified at several sites, and survived in mid-latitude Asia across climatic transitions for around 200,000 years. Our findings suggest that all three bovine taxa harbored diversity no longer present in extant populations, thus mirroring archaic hominin findings at Denisova Cave. The Altai mountains therefore appear to have been a hotspot of both bovine and hominin diversity.

Humans have relied on animal fur for centuries, yet fur farming only began recently during the mid-19th Century. Little is known about this incipient domestication or the genomic processes involved. Domestication may involve founder effects, population bottlenecks and low population size, which, when combined with intense artificial selection, lead to inbreeding, a limited gene pool and reduced fitness. The arctic fox (Vulpes lagopus) has been farmed intensively since the early 1900s and has been artificially selected for economic phenotypes. We investigated the origin of these lineages and the genomic consequences of intensive farming by comparing the genomes of farmed and wild arctic foxes from across their range. Our research indicates recent inbreeding through long Runs of Homozygosity and reduced genomic variation in farmed foxes relative to their respective wild populations. We identified a coastal ecotype origin for all Fennoscandian farmed arctic foxes, aligning them phylogenetically with the wild Icelandic population, a geographically isolated and phenotypically distinct coastal lineage. The depleted genome-wide heterozygosity and increased recent inbreeding in farmed fox lineages is consistent with a heavy consequence of domestication, shedding light on the demographic history and genomic consequences of human manipulation. We highlight the need for increased genomic investigations into fur farm populations to understand the incipient domestication process and uncover the cost of intense farming. The genomic consequences of domestication must be considered in the management of fur farms, with actionable steps needed to prevent descendants of escaped farmed foxes from polluting the gene pool in the wild through introgression.

A number of species have recently recovered from near-extinction. Although these species have avoided the immediate extinction threat, their long-term viability remains precarious due to the potential genetic consequences of population declines, which are poorly understood on a timescale beyond a few generations. Woolly mammoths (Mammuthus primigenius) became isolated on Wrangel Island around 10,000 years ago and persisted for over 200 generations before becoming extinct around 4,000 years ago. To study the evolutionary processes leading up to the mammoths’ extinction, we analyzed 21 Siberian woolly mammoth genomes. Our results show that the population recovered quickly from a severe bottleneck and remained demographically stable during the ensuing six millennia. We find that mildly deleterious mutations gradually accumulated, whereas highly deleterious mutations were purged, suggesting ongoing inbreeding depression that lasted for hundreds of generations. The time-lag between demographic and genetic recovery has wide-ranging implications for conservation management of recently bottlenecked populations.