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Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth's death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.
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Genoma , Mamuts , Piel , Animales , Mamuts/genética , Genoma/genética , Femenino , Elefantes/genética , Cromatina/genética , Fósiles , ADN Antiguo/análisis , Ratones , Humanos , Cromosoma X/genéticaRESUMEN
How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees.
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SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17ß-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.
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Primates , Animales , Humanos , Secuencia de Aminoácidos , Estradiol/metabolismo , Células HEK293 , Hominidae/genética , Hominidae/metabolismo , Mutación Missense , Proteínas de Transporte de Catión Orgánico/metabolismo , Proteínas de Transporte de Catión Orgánico/genética , Primates/genética , Seudogenes , Especificidad por SustratoRESUMEN
SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17ß-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.
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During the last century, the critically endangered cotton-top tamarin (Saguinus oedipus) has been threatened by multiple anthropogenic factors that drastically affected their habitat and population size. As the genetic impact of these pressures is largely unknown, this study aimed to establish a genetic baseline with the use of temporal sampling to determine the genetic makeup before detrimental anthropogenic impact. Genomes were resequenced from a combination of historical museum samples and modern wild samples at low-medium coverage, to unravel how the cotton-top tamarin population structure and genomic diversity may have changed during this period. Our data suggest two populations can be differentiated, probably separated historically by the mountain ranges of the Paramillo Massif in Colombia. Although this population structure persists in the current populations, modern samples exhibit genomic signals consistent with recent inbreeding, such as long runs of homozygosity and a reduction in genome-wide heterozygosity especially in the greater northeast population. This loss is likely the consequence of the population reduction following the mass exportation of cotton-top tamarins for biomedical research in the 1960s, coupled with the habitat loss this species continues to experience. However, current populations have not experienced an increase in genetic load. We propose that the historical genetic baseline established in this study can be used to provide insight into alteration in the modern population influenced by a drastic reduction in population size as well as providing background information to be used for future conservation decision-making for the species.
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SLC22A10 is classified as an orphan transporter with unknown substrates and function. Here we describe the discovery of the substrate specificity and functional characteristics of SLC22A10. The human SLC22A10 tagged with green fluorescent protein was found to be absent from the plasma membrane, in contrast to the SLC22A10 orthologs found in great apes. Estradiol-17ß-glucuronide accumulated in cells expressing great ape SLC22A10 orthologs (over 4-fold, p<0.001). In contrast, human SLC22A10 displayed no uptake function. Sequence alignments revealed two amino acid differences including a proline at position 220 of the human SLC22A10 and a leucine at the same position of great ape orthologs. Site-directed mutagenesis yielding the human SLC22A10-P220L produced a protein with excellent plasma membrane localization and associated uptake function. Neanderthal and Denisovan genomes show human-like sequences at proline 220 position, corroborating that SLC22A10 were rendered nonfunctional during hominin evolution after the divergence from the pan lineage (chimpanzees and bonobos). These findings demonstrate that human SLC22A10 is a unitary pseudogene and was inactivated by a missense mutation that is fixed in humans, whereas orthologs in great apes transport sex steroid conjugates.
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In endangered species, low-genetic variation and inbreeding result from recent population declines. Genetic screenings in endangered populations help to assess their vulnerability to extinction and to create informed management actions toward their conservation efforts. The leopard, Panthera pardus, is a highly generalist predator with currently eight different subspecies. Yet, genomic data are still lacking for the Critically Endangered Arabian leopard (P. p. nimr). Here, we sequenced the whole genome of two Arabian leopards and assembled the most complete genomic dataset for leopards to date. Our phylogenomic analyses show that leopards are divided into two deeply divergent clades: the African and the Asian. Conservation genomic analyses indicate a prolonged population decline, which has led to an increase in inbreeding and runs of homozygosity, with consequent purging of deleterious mutations in both Arabian individuals. Our study represents the first attempt to genetically inform captive breeding programmes for this Critically Endangered subspecies.
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The black rhinoceros (Diceros bicornis L.) is a critically endangered species historically distributed across sub-Saharan Africa. Hunting and habitat disturbance have diminished both its numbers and distribution since the 19th century, but a poaching crisis in the late 20th century drove them to the brink of extinction. Genetic and genomic assessments can greatly increase our knowledge of the species and inform management strategies. However, when a species has been severely reduced, with the extirpation and artificial admixture of several populations, it is extremely challenging to obtain an accurate understanding of historic population structure and evolutionary history from extant samples. Therefore, we generated and analyzed whole genomes from 63 black rhinoceros museum specimens collected between 1775 and 1981. Results showed that the black rhinoceros could be genetically structured into six major historic populations (Central Africa, East Africa, Northwestern Africa, Northeastern Africa, Ruvuma, and Southern Africa) within which were nested four further subpopulations (Maasailand, southwestern, eastern rift, and northern rift), largely mirroring geography, with a punctuated north-south cline. However, we detected varying degrees of admixture among groups and found that several geographical barriers, most prominently the Zambezi River, drove population discontinuities. Genomic diversity was high in the middle of the range and decayed toward the periphery. This comprehensive historic portrait also allowed us to ascertain the ancestry of 20 resequenced genomes from extant populations. Lastly, using insights gained from this unique temporal data set, we suggest management strategies, some of which require urgent implementation, for the conservation of the remaining black rhinoceros diversity.
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Evolución Biológica , Perisodáctilos , Animales , África Oriental , África del Sur del Sahara , Perisodáctilos/genética , Especies en Peligro de ExtinciónRESUMEN
The ongoing degradation of natural systems and other environmental changes has put our society at a crossroad with respect to our future relationship with our planet. While the concept of One Health describes how human health is inextricably linked with environmental health, many of these complex interdependencies are still not well-understood. Here, we describe how the advent of real-time genomic analyses can benefit One Health and how it can enable timely, in-depth ecosystem health assessments. We introduce nanopore sequencing as the only disruptive technology that currently allows for real-time genomic analyses and that is already being used worldwide to improve the accessibility and versatility of genomic sequencing. We showcase real-time genomic studies on zoonotic disease, food security, environmental microbiome, emerging pathogens, and their antimicrobial resistances, and on environmental health itself - from genomic resource creation for wildlife conservation to the monitoring of biodiversity, invasive species, and wildlife trafficking. We stress why equitable access to real-time genomics in the context of One Health will be paramount and discuss related practical, legal, and ethical limitations.
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Ecosistema , Salud Única , Humanos , Genómica , Biodiversidad , GenomaRESUMEN
Recent advances in long-read sequencing technologies have allowed the generation and curation of more complete genome assemblies, enabling the analysis of traditionally neglected chromosomes, such as the human Y chromosome (chrY). Native DNA was sequenced on a MinION Oxford Nanopore Technologies sequencing device to generate genome assemblies for seven major chrY human haplogroups. We analyzed and compared the chrY enrichment of sequencing data obtained using two different selective sequencing approaches: adaptive sampling and flow cytometry chromosome sorting. We show that adaptive sampling can produce data to create assemblies comparable to chromosome sorting while being a less expensive and time-consuming technique. We also assessed haplogroup-specific structural variants, which would be otherwise difficult to study using short-read sequencing data only. Finally, we took advantage of this technology to detect and profile epigenetic modifications among the considered haplogroups. Altogether, we provide a framework to study complex genomic regions with a simple, fast, and affordable methodology that could be applied to larger population genomics datasets.
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Epigenómica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Análisis de Secuencia de ADN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Genómica/métodos , Cromosoma YRESUMEN
Baboons (genus Papio) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high-coverage whole-genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and interspecies gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes.
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Evolución Biológica , Flujo Génico , Papio , Animales , Masculino , Papio/anatomía & histología , Papio/genética , Fenotipo , Filogenia , Especificidad de la Especie , Caracteres SexualesRESUMEN
Baboons (genus Papio ) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high coverage whole genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and inter-species gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal novel patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes. One-Sentence Summary: Genomic data for 225 baboons reveal novel sites of inter-species gene flow and local effects due to differences in admixture.
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The critically endangered western gorillas (Gorilla gorilla) are divided into two subspecies: the western lowland (G. g. gorilla) and the Cross River (G. g. diehli) gorilla. Given the difficulty in sampling wild great ape populations and the small estimated size of the Cross River gorilla population, only one whole genome of a Cross River gorilla has been sequenced to date, hindering the study of this subspecies at the population level. In this study, we expand the number of whole genomes available for wild western gorillas, generating 41 new genomes (25 belonging to Cross River gorillas) using single shed hairs collected from gorilla nests. By combining these genomes with publicly available wild gorilla genomes, we confirm that Cross River gorillas form three population clusters. We also found little variation in genome-wide heterozygosity among them. Our analyses reveal long runs of homozygosity (>10 Mb), indicating recent inbreeding in Cross River gorillas. This is similar to that seen in mountain gorillas but with a much more recent bottleneck. We also detect past gene flow between two Cross River sites, Afi Mountain Wildlife Sanctuary and the Mbe Mountains. Furthermore, we observe past allele sharing between Cross River gorillas and the northern western lowland gorilla sites, as well as with the eastern gorilla species. This is the first study using single shed hairs from a wild species for whole genome sequencing to date. Taken together, our results highlight the importance of implementing conservation measures to increase connectivity among Cross River gorilla sites.
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Gorilla gorilla , Hominidae , Animales , Humanos , Gorilla gorilla/genética , Endogamia , Hominidae/genética , Genoma/genética , Flujo GénicoRESUMEN
Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees.
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Captive breeding programmes represent the most intensive type of ex situ population management for threatened species. One example is the Cuvier's gazelle programme that started in 1975 with only four founding individuals, and after more than four decades of management in captivity, a reintroduction effort was undertaken in Tunisia in 2016, to establish a population in an area historically included within its range. Here, we aim to determine the genetic consequences of this reintroduction event by assessing the genetic diversity of the founder stock as well as of their descendants. We present the first whole-genome sequencing dataset of 30 Cuvier's gazelles including captive-bred animals, animals born in Tunisia after a reintroduction and individuals from a genetically unrelated Moroccan population. Our analyses revealed no difference between the founder and the offspring cohorts in genome-wide heterozygosity and inbreeding levels, and in the amount and length of runs of homozygosity. The captive but unmanaged Moroccan gazelles have the lowest genetic diversity of all genomes analysed. Our findings demonstrate that the Cuvier's gazelle captive breeding programme can serve as source populations for future reintroductions of this species. We believe that this study can serve as a starting point for global applications of genomics to the conservation plan of this species.
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BACKGROUND: Numerous Ebola virus outbreaks have occurred in Equatorial Africa over the past decades. Besides human fatalities, gorillas and chimpanzees have also succumbed to the fatal virus. The 2004 outbreak at the Odzala-Kokoua National Park (Republic of Congo) alone caused a severe decline in the resident western lowland gorilla (Gorilla gorilla gorilla) population, with a 95% mortality rate. Here, we explore the immediate genetic impact of the Ebola outbreak in the western lowland gorilla population. RESULTS: Associations with survivorship were evaluated by utilizing DNA obtained from fecal samples from 16 gorilla individuals declared missing after the outbreak (non-survivors) and 15 individuals observed before and after the epidemic (survivors). We used a target enrichment approach to capture the sequences of 123 genes previously associated with immunology and Ebola virus resistance and additionally analyzed the gut microbiome which could influence the survival after an infection. Our results indicate no changes in the population genetic diversity before and after the Ebola outbreak, and no significant differences in microbial community composition between survivors and non-survivors. However, and despite the low power for an association analysis, we do detect six nominally significant missense mutations in four genes that might be candidate variants associated with an increased chance of survival. CONCLUSION: This study offers the first insight to the genetics of a wild great ape population before and after an Ebola outbreak using target capture experiments from fecal samples, and presents a list of candidate loci that may have facilitated their survival.
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Microbioma Gastrointestinal , Fiebre Hemorrágica Ebola , Animales , Brotes de Enfermedades , Gorilla gorilla/genética , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/veterinaria , Humanos , Pan troglodytesRESUMEN
Modern human contamination is a common problem in ancient DNA studies. We provide evidence that this issue is also present in studies in great apes, which are our closest living relatives, for example in noninvasive samples. Here, we present a simple method to detect human contamination in short-read sequencing data from different species: HuConTest. We demonstrate its feasibility using blood and tissue samples from these species. This test is particularly useful for more complex samples (such as museum and noninvasive samples) which have smaller amounts of endogenous DNA, as we show here.
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Contaminación de ADN , Hominidae/genética , Animales , HumanosRESUMEN
Ecological flexibility, extended lifespans, and large brains have long intrigued evolutionary biologists, and comparative genomics offers an efficient and effective tool for generating new insights into the evolution of such traits. Studies of capuchin monkeys are particularly well situated to shed light on the selective pressures and genetic underpinnings of local adaptation to diverse habitats, longevity, and brain development. Distributed widely across Central and South America, they are inventive and extractive foragers, known for their sensorimotor intelligence. Capuchins have among the largest relative brain size of any monkey and a lifespan that exceeds 50 y, despite their small (3 to 5 kg) body size. We assemble and annotate a de novo reference genome for Cebus imitator Through high-depth sequencing of DNA derived from blood, various tissues, and feces via fluorescence-activated cell sorting (fecalFACS) to isolate monkey epithelial cells, we compared genomes of capuchin populations from tropical dry forests and lowland rainforests and identified population divergence in genes involved in water balance, kidney function, and metabolism. Through a comparative genomics approach spanning a wide diversity of mammals, we identified genes under positive selection associated with longevity and brain development. Additionally, we provide a technological advancement in the use of noninvasive genomics for studies of free-ranging mammals. Our intra- and interspecific comparative study of capuchin genomics provides insights into processes underlying local adaptation to diverse and physiologically challenging environments, as well as the molecular basis of brain evolution and longevity.
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Adaptación Fisiológica , Encéfalo/crecimiento & desarrollo , Cebus/genética , Genoma , Longevidad/genética , Animales , Evolución Molecular , Citometría de Flujo/métodos , Bosques , Genómica/métodosRESUMEN
Noninvasive samples as a source of DNA are gaining interest in genomic studies of endangered species. However, their complex nature and low endogenous DNA content hamper the recovery of good quality data. Target capture has become a productive method to enrich the endogenous fraction of noninvasive samples, such as faeces, but its sensitivity has not yet been extensively studied. Coping with faecal samples with an endogenous DNA content below 1% is a common problem when prior selection of samples from a large collection is not possible. However, samples classified as unfavourable for target capture sequencing might be the only representatives of unique specific geographical locations, or to answer the question of interest. To explore how library complexity may be increased without repeating DNA extractions and generating new libraries, in this study we captured the exome of 60 chimpanzees (Pan troglodytes) using faecal samples with very low proportions of endogenous content (<1%). Our results indicate that by performing additional hybridizations of the same libraries, the molecular complexity can be maintained to achieve higher coverage. Also, whenever possible, the starting DNA material for capture should be increased. Finally, we specifically calculated the sequencing effort needed to avoid exhausting the library complexity of enriched faecal samples with low endogenous DNA content. This study provides guidelines, schemes and tools for laboratories facing the challenges of working with noninvasive samples containing extremely low amounts of endogenous DNA.
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Exoma , Genómica , Hibridación de Ácido Nucleico , Animales , Heces , Biblioteca de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Pan troglodytes/genética , Análisis de Secuencia de ADNRESUMEN
Populations of the common chimpanzee (Pan troglodytes) are in an impending risk of going extinct in the wild as a consequence of damaging anthropogenic impact on their natural habitat and illegal pet and bushmeat trade. Conservation management programmes for the chimpanzee have been established outside their natural range (ex situ), and chimpanzees from these programmes could potentially be used to supplement future conservation initiatives in the wild (in situ). However, these programmes have often suffered from inadequate information about the geographical origin and subspecies ancestry of the founders. Here, we present a newly designed capture array with ~60,000 ancestry informative markers used to infer ancestry of individual chimpanzees in ex situ populations and determine geographical origin of confiscated sanctuary individuals. From a test panel of 167 chimpanzees with unknown origins or subspecies labels, we identify 90 suitable non-admixed individuals in the European Association of Zoos and Aquaria (EAZA) Ex situ Programme (EEP). Equally important, another 46 individuals have been identified with admixed subspecies ancestries, which therefore over time, should be naturally phased out of the breeding populations. With potential for future re-introduction to the wild, we determine the geographical origin of 31 individuals that were confiscated from the illegal trade and demonstrate the promises of using non-invasive sampling in future conservation action plans. Collectively, our genomic approach provides an exemplar for ex situ management of endangered species and offers an efficient tool in future in situ efforts to combat the illegal wildlife trade.