Genomic analysis supports Cape Lion population connectivity prior to colonial eradication and extinction.

Cape lions (Panthera leo melanochaitus) formerly ranged throughout the grassland plains of the "Cape Flats" in what is today known as the Western Cape Province, South Africa. Cape lions were likely eradicated because of overhunting and habitat loss after European colonization. European naturalists originally described Cape lions as "black-maned lions" and claimed that they were phenotypically distinct. However, other depictions and historical descriptions of lions from the Cape report mixed or light coloration and without black or extensively developed manes. These findings suggest that, rather than forming a distinct population, Cape lions may have had phenotypic and genotypic variation similar to other African lions. Here we investigate Cape lion genome characteristics, population dynamics, and genetic distinctiveness prior to their extinction. We generated genomic data from 2 historic Cape lions to compare to 118 existing high-coverage mitogenomes, and low-coverage nuclear genomes of 53 lions from 13 African countries. We show that, before their eradication, lions from the Cape Flats had diverse mitogenomes and nuclear genomes that clustered with lions from both southern and eastern Africa. Cape lions had high genome-wide heterozygosity and low inbreeding coefficients, indicating that populations in the Cape Flats went extinct so rapidly that genomic effects associated with long-term small population size and isolation were not detectable. Our findings do not support the characterization of Cape lions as phylogeographically distinct, as originally put forth by some European naturalists, and illustrates how alternative knowledge systems, for example, Indigenous perspectives, could potentially further inform interpretations of species histories.

Pharmacogenetic Variation in Neanderthals and Denisovans and Implications for Human Health and Response to Medications.

Modern humans carry both Neanderthal and Denisovan (archaic) genome elements that are part of the human gene pool and affect the life and health of living individuals. The impact of archaic DNA may be particularly evident in pharmacogenes-genes responsible for the processing of exogenous substances such as food, pollutants, and medications-as these can relate to changing environmental effects, and beneficial variants may have been retained as modern humans encountered new environments. However, the health implications and contribution of archaic ancestry in pharmacogenes of modern humans remain understudied. Here, we explore 11 key cytochrome P450 genes (CYP450) involved in 75% of all drug metabolizing reactions in three Neanderthal and one Denisovan individuals and examine archaic introgression in modern human populations. We infer the metabolizing efficiency of these 11 CYP450 genes in archaic individuals and find important predicted phenotypic differences relative to modern human variants. We identify several single nucleotide variants shared between archaic and modern humans in each gene, including some potentially function-altering mutations in archaic CYP450 genes, which may result in altered metabolism in living people carrying these variants. We also identified several variants in the archaic CYP450 genes that are novel and unique to archaic humans as well as one gene, CYP2B6, that shows evidence for a gene duplication found only in Neanderthals and modern Africans. Finally, we highlight CYP2A6, CYP2C9, and CYP2J2, genes which show evidence for archaic introgression into modern humans and posit evolutionary hypotheses that explain their allele frequencies in modern populations.

The MUC19 gene in Denisovans, Neanderthals, and Modern Humans: An Evolutionary History of Recurrent Introgression and Natural Selection.

All humans carry a small fraction of archaic ancestry across the genome, the legacy of gene flow from Neanderthals, Denisovans, and other hominids into the ancestors of modern humans. While the effects of Neanderthal ancestry on human fitness and health have been explored more thoroughly, there are fewer examples of adaptive introgression of Denisovan variants. Here, we study the gene MUC19, for which some modern humans carry a Denisovan-like haplotype. MUC19 is a mucin, a glycoprotein that forms gels with various biological functions, from lubrication to immunity. We find the diagnostic variants for the Denisovan-like MUC19 haplotype at high frequencies in admixed Latin American individuals among global population, and at highest frequency in 23 ancient Indigenous American individuals, all predating population admixture with Europeans and Africans. We find that some Neanderthals--Vindija and Chagyrskaya--carry the Denisovan-like MUC19 haplotype, and that it was likely introgressed into human populations through Neanderthal introgression rather than Denisovan introgression. Finally, we find that the Denisovan-like MUC19 haplotype carries a higher copy number of a 30 base-pair variable number tandem repeat relative to the Human-like haplotype, and that copy numbers of this repeat are exceedingly high in American populations. Our results suggest that the Denisovan-like MUC19 haplotype served as the raw genetic material for positive selection as American populations adapted to novel environments during their movement from Beringia into North and then South America.

Ancient Mongolian aurochs genomes reveal sustained introgression and management in East Asia.

Societies in East Asia have utilized domesticated cattle for over 5000 years, but the genetic history of cattle in East Asia remains understudied. Genome-wide analyses of 23 ancient Mongolian cattle reveal that East Asian aurochs and ancient East Asian taurine cattle are closely related, but neither are closely related to any modern East Asian breeds. We observe binary variation in aurochs diet throughout the early Neolithic, and genomic evidence shows millennia of sustained male-dominated introgression. We identify a unique connection between ancient Mongolian aurochs and the European Hereford breed. These results point to the likelihood of human management of aurochs in Northeast Asia prior to and during the initial adoption of taurine cattle pastoralism.

The Impact of Modern Admixture on Archaic Human Ancestry in Human Populations.

Admixture, the genetic merging of parental populations resulting in mixed ancestry, has occurred frequently throughout the course of human history. Numerous admixture events have occurred between human populations across the world, which have shaped genetic ancestry in modern humans. For example, populations in the Americas are often mosaics of different ancestries due to recent admixture events as part of European colonization. Admixed individuals also often have introgressed DNA from Neanderthals and Denisovans that may have come from multiple ancestral populations, which may affect how archaic ancestry is distributed across an admixed genome. In this study, we analyzed admixed populations from the Americas to assess whether the proportion and location of admixed segments due to recent admixture impact an individual's archaic ancestry. We identified a positive correlation between non-African ancestry and archaic alleles, as well as a slight increase of Denisovan alleles in Indigenous American segments relative to European segments in admixed genomes. We also identify several genes as candidates for adaptive introgression, based on archaic alleles present at high frequency in admixed American populations but low frequency in East Asian populations. These results provide insights into how recent admixture events between modern humans redistributed archaic ancestry in admixed genomes.

The impact of modern admixture on archaic human ancestry in human populations.

Admixture, the genetic merging of parental populations resulting in mixed ancestry, has occurred frequently throughout the course of human history. Numerous admixture events have occurred between human populations across the world, as well as introgression between humans and archaic humans, Neanderthals and Denisovans. One example are genomes from populations in the Americas, as these are often mosaics of different ancestries due to recent admixture events as part of European colonization. In this study, we analyzed admixed populations from the Americas to assess whether the proportion and location of admixed segments due to recent admixture impact an individual’s archaic ancestry. We identified a positive correlation between non-African ancestry and archaic alleles, as well as a slight enrichment of Denisovan alleles in Indigenous American segments relative to European segments in admixed genomes. We also identify several genes as candidates for adaptive introgression, based on archaic alleles present at high frequency in admixed American populations but low frequency in East Asian populations. These results provide insights into how recent admixture events between modern humans redistributed archaic ancestry in admixed genomes.

Apportioning archaic variants among modern populations.

The apportionment of human genetic diversity within and between populations has been measured to understand human relatedness and demographic history. Likewise, the distribution of archaic ancestry in modern populations can be leveraged to better understand the interaction between our species and its archaic relatives. Resolving the interactions between modern and archaic human populations can be difficult, as archaic variants in modern populations have been shaped by genetic drift, bottlenecks and gene flow. Here, we investigate the distribution of archaic variation in Eurasian populations. We find that archaic ancestry coverage at the individual- and population-level present distinct patterns in modern human populations: South Asians have nearly twice the number of population-unique archaic alleles compared with Europeans or East Asians, indicating that these populations experienced differing demographic and archaic admixture events. We confirm previous observations that East Asian individuals have more Neanderthal ancestry than European individuals, but surprisingly, when we compare the number of single nucleotide polymorphisms with archaic alleles found across a population, Europeans have more Neanderthal ancestry than East Asians. We compare these results to simulated models and conclude that these patterns are consistent with multiple admixture events between modern humans and Neanderthals. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.

The history and evolution of the Denisovan-EPAS1 haplotype in Tibetans.

Recent studies suggest that admixture with archaic hominins played an important role in facilitating biological adaptations to new environments. For example, interbreeding with Denisovans facilitated the adaptation to high-altitude environments on the Tibetan Plateau. Specifically, the EPAS1 gene, a transcription factor that regulates the response to hypoxia, exhibits strong signatures of both positive selection and introgression from Denisovans in Tibetan individuals. Interestingly, despite being geographically closer to the Denisova Cave, East Asian populations do not harbor as much Denisovan ancestry as populations from Melanesia. Recently, two studies have suggested two independent waves of Denisovan admixture into East Asians, one of which is shared with South Asians and Oceanians. Here, we leverage data from EPAS1 in 78 Tibetan individuals to interrogate which of these two introgression events introduced the EPAS1 beneficial sequence into the ancestral population of Tibetans, and we use the distribution of introgressed segment lengths at this locus to infer the timing of the introgression and selection event. We find that the introgression event unique to East Asians most likely introduced the beneficial haplotype into the ancestral population of Tibetans around 48,700 (16,000-59,500) y ago, and selection started around 9,000 (2,500-42,000) y ago. Our estimates suggest that one of the most convincing examples of adaptive introgression is in fact selection acting on standing archaic variation.

Our Tangled Family Tree: New Genomic Methods Offer Insight into the Legacy of Archaic Admixture.

The archaic ancestry present in the human genome has captured the imagination of both scientists and the wider public in recent years. This excitement is the result of new studies pushing the envelope of what we can learn from the archaic genetic information that has survived for over 50,000 years in the human genome. Here, we review the most recent ten years of literature on the topic of archaic introgression, including the current state of knowledge on Neanderthal and Denisovan introgression, as well as introgression from other as-yet unidentified archaic populations. We focus this review on four topics: 1) a reimagining of human demographic history, including evidence for multiple admixture events between modern humans, Neanderthals, Denisovans, and other archaic populations; 2) state-of-the-art methods for detecting archaic ancestry in population-level genomic data; 3) how these novel methods can detect archaic introgression in modern African populations; and 4) the functional consequences of archaic gene variants, including how those variants were co-opted into novel function in modern human populations. The goal of this review is to provide a simple-to-access reference for the relevant methods and novel data, which has changed our understanding of the relationship between our species and its siblings. This body of literature reveals the large degree to which the genetic legacy of these extinct hominins has been integrated into the human populations of today.

Integrative analysis of DNA, macroscopic remains and stable isotopes of dog coprolites to reconstruct community diet.

Paleofeces or coprolites are often used to reconstruct diet at archaeological sites, usually using macroscopic analyses or targeted DNA amplification and sequencing. Here we present an integrative analysis of dog coprolites, combining macroscopic analyses, stable isotope measurements, and DNA shotgun sequencing to examine diet and health status. Dog coprolites used in this study were recovered from the Janey B. Goode and East Saint Louis archaeological sites, both of which are located in the American Bottom, an extensive Mississippi River floodplain in Southwestern Illinois. Based on the context of recovery, coprolites are assigned to the Late Woodland and Terminal Late Woodland periods (ca. 600-1050 AD). Given the scarcity of human remains from this time period, these dog coprolites can be useful as a proxy for understanding human diet during the Late Woodland period. We find that the Late Woodland dogs consumed a variety of fish as well as bird and plant taxa, possibly including maize, and also harbored intestinal parasites and pathogenic bacteria. By sequencing the fecal microbiome of the coprolites, we find some similarities to modern dog microbiomes, as well as specific taxa that can be used to discriminate between modern and ancient microbiomes, excluding soil contaminants. As dogs are often used as a surrogate to assess human diet, humans living with these dogs likely had a similar diet and were affected by similar parasites. These analyses, when integrated, show a more comprehensive view of ancient dog and human diet and health in the region during the initial expansion of maize agriculture than any individual method could alone.

Dog domestication and the dual dispersal of people and dogs into the Americas.

Advances in the isolation and sequencing of ancient DNA have begun to reveal the population histories of both people and dogs. Over the last 10,000 y, the genetic signatures of ancient dog remains have been linked with known human dispersals in regions such as the Arctic and the remote Pacific. It is suspected, however, that this relationship has a much deeper antiquity, and that the tandem movement of people and dogs may have begun soon after the domestication of the dog from a gray wolf ancestor in the late Pleistocene. Here, by comparing population genetic results of humans and dogs from Siberia, Beringia, and North America, we show that there is a close correlation in the movement and divergences of their respective lineages. This evidence places constraints on when and where dog domestication took place. Most significantly, it suggests that dogs were domesticated in Siberia by ∼23,000 y ago, possibly while both people and wolves were isolated during the harsh climate of the Last Glacial Maximum. Dogs then accompanied the first people into the Americas and traveled with them as humans rapidly dispersed into the continent beginning ∼15,000 y ago.

Ancient DNA suggests modern wolves trace their origin to a Late Pleistocene expansion from Beringia.

Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that have maintained a wide geographical distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the Late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single Late Pleistocene population. Both the geographical origin of this ancestral population and how it became widespread remain unknown. Here, we used a spatially and temporally explicit modelling framework to analyse a data set of 90 modern and 45 ancient mitochondrial wolf genomes from across the Northern Hemisphere, spanning the last 50,000 years. Our results suggest that contemporary wolf populations trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum, and that this process was most likely driven by Late Pleistocene ecological fluctuations that occurred across the Northern Hemisphere. This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore, and provides insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because Late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog.

Ancient DNA from a 2,500-year-old Caribbean fossil places an extinct bird (Caracara creightoni) in a phylogenetic context.

Since the late Pleistocene humans have caused the extinction of species across our planet. Placing these extinct species in the tree of life with genetic data is essential to understanding the ecological and evolutionary implications of these losses. While ancient DNA (aDNA) techniques have advanced rapidly in recent decades, aDNA from tropical species, especially birds, has been historically difficult to obtain, leaving a gap in our knowledge of the extinction processes that have influenced current distributions and biodiversity. Here we report the recovery of a nearly complete mitochondrial genome from a 2,500 year old (late Holocene) bone of an extinct species of bird, Caracara creightoni, recovered from the anoxic saltwater environment of a blue hole in the Bahamas. Our results suggest that this extinct species is sister (1.6% sequence divergence) to a clade containing the extant C. cheriway and C. plancus. Caracara creightoni shared a common ancestor with these extant species during the Pleistocene (1.2-0.4 MYA) and presumably survived on Cuba when the Bahamas was mostly underwater during Quaternary interglacial intervals (periods of high sea levels). Tropical blue holes have been collecting animals for thousands of years and will continue to improve our understanding of faunal extinctions and distributions. In particular, new aDNA techniques combined with radiocarbon dating from Holocene Bahamian fossils will allow us to place other extinct (species-level loss) and extirpated (population-level loss) vertebrate taxa in improved phylogenetic, evolutionary, biogeographic, and temporal contexts.

Convergent evolution in human and domesticate adaptation to high-altitude environments.

Humans and their domestic animals have lived and thrived in high-altitude environments worldwide for thousands of years. These populations have developed a number of adaptations to survive in a hypoxic environment, and several genomic studies have been conducted to identify the genes that drive these adaptations. Here, we discuss the various adaptations and genetic variants that have been identified as adaptive in human and domestic animal populations and the ways in which convergent evolution has occurred as these populations have adapted to high-altitude environments. We found that human and domesticate populations have adapted to hypoxic environments in similar ways. Specific genes and biological pathways have been involved in high-altitude adaptation for multiple populations, although the specific variants differ between populations. Additionally, we found that the gene EPAS1 is often a target of selection in hypoxic environments and has been involved in multiple adaptive introgression events. High-altitude environments exert strong selective pressures, and human and animal populations have evolved in convergent ways to cope with a chronic lack of oxygen. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.

The evolutionary history of dogs in the Americas.

Dogs were present in the Americas before the arrival of European colonists, but the origin and fate of these precontact dogs are largely unknown. We sequenced 71 mitochondrial and 7 nuclear genomes from ancient North American and Siberian dogs from time frames spanning ~9000 years. Our analysis indicates that American dogs were not derived from North American wolves. Instead, American dogs form a monophyletic lineage that likely originated in Siberia and dispersed into the Americas alongside people. After the arrival of Europeans, native American dogs almost completely disappeared, leaving a minimal genetic legacy in modern dog populations. The closest detectable extant lineage to precontact American dogs is the canine transmissible venereal tumor, a contagious cancer clone derived from an individual dog that lived up to 8000 years ago.

Genetic Structure and Diversity Among Historic and Modern Populations of the Sumatran Rhinoceros (Dicerorhinus sumatrensis).

The Sumatran rhinoceros (Dicerorhinus sumatrensis), once widespread across Southeast Asia, now consists of as few as 30 individuals within Sumatra and Borneo. To aid in conservation planning, we sequenced 218 bp of control region mitochondrial (mt) DNA, identifying 17 distinct mitochondrial haplotypes across modern (N = 13) and museum (N = 26) samples. Museum specimens from Laos and Myanmar had divergent mtDNA, consistent with the placement of western mainland rhinos into the distinct subspecies D. s. lasiotis (presumed extinct). Haplotypes from Bornean rhinos were highly diverse, but dissimilar from those of other regions, supporting the distinctiveness of the subspecies D. s. harrissoni. Rhinos from Sumatra and Peninsular Malaysia shared mtDNA haplotypes, consistent with their traditional placement into a single subspecies D. s sumatrensis. Modern samples of D. s. sumatrensis were genotyped at 18 microsatellite loci. Rhinos within Sumatra formed 2 sub-populations, likely separated by the Barisan Mountains, though with only modest genetic differentiation between them. There are so few remaining Sumatran rhinoceros that separate management strategies for subspecies or subpopulations may not be viable, while each surviving rhino pedigree is likely to retain alleles found in no other individuals. Given the low population size and low reproductive potential of Sumatran rhinos, rapid genetic erosion is inevitable, though an under-appreciated concern is the potential for fixation of harmful genetic variants. Both concerns underscore 2 overriding priorities for the species: 1) translocation of wild rhinos to ex situ facilities, and 2) collection and storage of gametes and cell lines from every surviving captive and wild individual.

DNA analysis of ancient dogs of the Americas: identifying possible founding haplotypes and reconstructing population histories.

As dogs have traveled with humans to every continent, they can potentially serve as an excellent proxy when studying human migration history. Past genetic studies into the origins of Native American dogs have used portions of the hypervariable region (HVR) of mitochondrial DNA (mtDNA) to indicate that prior to European contact the dogs of Native Americans originated in Eurasia. In this study, we summarize past DNA studies of both humans and dogs to discuss their population histories in the Americas. We then sequenced a portion of the mtDNA HVR of 42 pre-Columbian dogs from three sites located in Illinois, coastal British Columbia, and Colorado, and identify four novel dog mtDNA haplotypes. Next, we analyzed a dataset comprised of all available ancient dog sequences from the Americas to infer the pre-Columbian population history of dogs in the Americas. Interestingly, we found low levels of genetic diversity for some populations consistent with the possibility of deliberate breeding practices. Furthermore, we identified multiple putative founding haplotypes in addition to dog haplotypes that closely resemble those of wolves, suggesting admixture with North American wolves or perhaps a second domestication of canids in the Americas. Notably, initial effective population size estimates suggest at least 1000 female dogs likely existed in the Americas at the time of the first known canid burial, and that population size increased gradually over time before stabilizing roughly 1200 years before present.