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Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6, and GM11545 with bone mineral density, and Psmb9 with weight. However, replication at a nominal threshold of 0.05 between the two component studies was low, with less than one-third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner's Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Leveraging these observations, we integrated information about replication rates, study-specific heterogeneity, and Winner's Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study. [ABSTRACT FROM AUTHOR]

Large vertebrates are extremely sensitive to anthropogenic pressure, and their populations are declining fast. The white rhinoceros (Ceratotherium simum) is a paradigmatic case: this African megaherbivore has suffered a remarkable decline in the last 150 years due to human activities. Its subspecies, the northern (NWR) and the southern white rhinoceros (SWR), however, underwent opposite fates: the NWR vanished quickly, while the SWR recovered after the severe decline. Such demographic events are predicted to have an erosive effect at the genomic level, linked to the extirpation of diversity, and increased genetic drift and inbreeding. However, there is little empirical data available to directly reconstruct the subtleties of such processes in light of distinct demographic histories. Therefore, we generated a whole‐genome, temporal data set consisting of 52 resequenced white rhinoceros genomes, representing both subspecies at two time windows: before and during/after the bottleneck. Our data reveal previously unknown population structure within both subspecies, as well as quantifiable genomic erosion. Genome‐wide heterozygosity decreased significantly by 10% in the NWR and 36% in the SWR, and inbreeding coefficients rose significantly by 11% and 39%, respectively. Despite the remarkable loss of genomic diversity and recent inbreeding it suffered, the only surviving subspecies, the SWR, does not show a significant accumulation of genetic load compared to its historical counterpart. Our data provide empirical support for predictions about the genomic consequences of shrinking populations, and our findings have the potential to inform the conservation efforts of the remaining white rhinoceroses. [ABSTRACT FROM AUTHOR]

One of the simplest problems involving external vorticity in boundary layer flows is the flow over a semi-infinite plate under a stream of uniform shear. We study the transient growth phenomenon in this flow to investigate the role of freestream shear on energy amplification and analyze the differences with the Blasius flow. The initial optimal disturbance that triggers the maximum growth is found to be streamwise vortices, as in other shear flows. Compared to the Blasius boundary layer, higher optimum energy and larger spanwise wavelength of streamwise vortices have been observed. We provide scaling laws for the maximum optimal amplification, which is found to increase exponentially with the freestream shear gradient. [ABSTRACT FROM AUTHOR]

Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog–specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago. [ABSTRACT FROM AUTHOR]

The third millennium BCE was a period of major cultural and demographic changes in Europe that signaled the beginning of the Bronze Age. People from the Pontic steppe expanded westward, leading to the formation of the Corded Ware complex and transforming the genetic landscape of Europe. At the time, the Globular Amphora culture (3300-2700 BCE) existed over large parts of Central and Eastern Europe, but little is known about their interaction with neighboring Corded Ware groups and steppe societies. Here we present a detailed study of a Late Neolithic mass grave from southern Poland belonging to the Globular Amphora culture and containing the remains of 15 men, women, and children, all killed by blows to the head. We sequenced their genomes to between 1.1- and 3.9-fold coverage and performed kinship analyses that demonstrate that the individuals belonged to a large extended family. The bodies had been carefully laid out according to kin relationships by someone who evidently knew the deceased. From a population genetic viewpoint, the people from Koszyce are clearly distinct from neighboring Corded Ware groups because of their lack of steppe-related ancestry. Although the reason for the massacre is unknown, it is possible that it was connected with the expansion of Corded Ware groups, which may have resulted in competition for resources and violent conflict. Together with the archaeological evidence, these analyses provide an unprecedented level of insight into the kinship structure and social behavior of a Late Neolithic community. [ABSTRACT FROM AUTHOR]

Abstract: Metabarcoding diet analysis has become a valuable tool in animal ecology; however, co‐amplified predator sequences are not generally used for anything other than to validate predator identity. Exemplified by the common vampire bat, we demonstrate the use of metabarcoding to infer predator population structure alongside diet assessments. Growing populations of common vampire bats impact human, livestock and wildlife health in Latin America through transmission of pathogens, such as lethal rabies viruses. Techniques to determine large‐scale variation in vampire bat diet and bat population structure would empower locality‐ and species‐specific projections of disease transmission risks. However, previously used methods are not cost‐effective and efficient for large‐scale applications. Using bloodmeal and faecal samples from common vampire bats from coastal, Andean and Amazonian regions of Peru, we showcase metabarcoding as a scalable tool to assess vampire bat population structure and feeding preferences. Dietary metabarcoding was highly effective, detecting vertebrate prey in 93.2% of the samples. Bats predominantly preyed on domestic animals, but fed on tapirs at one Amazonian site. In addition, we identified arthropods in 9.3% of samples, likely reflecting consumption of ectoparasites. Using the same data, we document mitochondrial geographic population structure in the common vampire bat in Peru. Such simultaneous inference of vampire bat diet and population structure can enable new insights into the interplay between vampire bat ecology and disease transmission risks. Importantly, the methodology can be incorporated into metabarcoding diet studies of other animals to couple information on diet and population structure. [ABSTRACT FROM AUTHOR]

Ancient DNA research has been revolutionized following development of next-generation sequencing platforms. Although a number of such platforms have been applied to ancient DNA samples, the Illumina series are the dominant choice today, mainly because of high production capacities and short read production. Recently a potentially attractive alternative platform for palaeogenomic data generation has been developed, the BGISEQ-500, whose sequence output are comparable with the Illumina series. In this study, we modified the standard BGISEQ-500 library preparation specifically for use on degraded DNA, then directly compared the sequencing performance and data quality of the BGISEQ-500 to the Illumina HiSeq2500 platform on DNA extracted from 8 historic and ancient dog and wolf samples. The data generated were largely comparable between sequencing platforms, with no statistically significant difference observed for parameters including level (P = 0.371) and average sequence length (P = 0718) of endogenous nuclear DNA, sequence GC content (P = 0.311), double-stranded DNA damage rate (v. 0.309), and sequence clonality (P = 0.093). Small significant differences were found in single-strand DNA damage rate (dS; slightly lower for the BGISEQ-500, P = 0.011) and the background rate of difference from the reference genome (θ; slightly higher for BGISEQ-500, P = 0.012). This may result from the differences in amplification cycles used to polymerase chain reaction-amplify the libraries. A significant difference was also observed in the mitochondrial DNA percentages recovered (P = 0.018), although we believe this is likely a stochastic effect relating to the extremely low levels of mitochondria that were sequenced from 3 of the samples with overall very low levels of endogenous DNA. Although we acknowledge that our analyses were limited to animal material, our observations suggest that the BGISEQ-500 holds the potential to represent a valid and potentially valuable alternative platform for palaeogenomic data generation that is worthy of future exploration by those interested in the sequencing and analysis of degraded DNA. [ABSTRACT FROM AUTHOR]

Background: An increasing number of studies are addressing the evolutionary genomics of dog domestication, principally through resequencing dog, wolf and related canid genomes. There is, however, only one de novo assembled canid genome currently available against which to map such data - that of a boxer dog (Canis lupus familiaris). We generated the first de novo wolf genome (Canis lupus lupus) as an additional choice of reference, and explored what implications may arise when previously published dog and wolf resequencing data are remapped to this reference. Results: Reassuringly, we find that regardless of the reference genome choice, most evolutionary genomic analyses yield qualitatively similar results, including those exploring the structure between the wolves and dogs using admixture and principal component analysis. However, we do observe differences in the genomic coverage of re-mapped samples, the number of variants discovered, and heterozygosity estimates of the samples. Conclusion: In conclusion, the choice of reference is dictated by the aims of the study being undertaken; if the study focuses on the differences between the different dog breeds or the fine structure among dogs, then using the boxer reference genome is appropriate, but if the aim of the study is to look at the variation within wolves and their relationships to dogs, then there are clear benefits to using the de novo assembled wolf reference genome. [ABSTRACT FROM AUTHOR]

Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%. 1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis). 2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large F ST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics. • The second plague pandemic homogenized ancestry in Trondheim • Gaelic ancestry is sharply reduced in post-pandemic Trondheim • Pervasive reference bias taints frequency differences observed between populations Gopalakrishnan et al. investigate the genomic signatures of the second plague pandemic on the residents of Trondheim in Norway. They find that the pandemic resulted in a sharp reduction in Gaelic ancestry and also find evidence of differential reference bias among their ancient samples, which reduces the reliability of selection analyses. [ABSTRACT FROM AUTHOR]

Current mitochondrial DNA (mtDNA) haplogroup classification tools map reads to a single reference genome and perform inference based on the detected mutations to this reference. This approach biases haplogroup assignments towards the reference and prohibits accurate calculations of the uncertainty in assignment. We present HaploCart, a probabilistic mtDNA haplogroup classifier which uses a pangenomic reference graph framework together with principles of Bayesian inference. We demonstrate that our approach significantly outperforms available tools by being more robust to lower coverage or incomplete consensus sequences and producing phylogenetically-aware confidence scores that are unbiased towards any haplogroup. HaploCart is available both as a command-line tool and through a user-friendly web interface. The C++ program accepts as input consensus FASTA, FASTQ, or GAM files, and outputs a text file with the haplogroup assignments of the samples along with the level of confidence in the assignments. Our work considerably reduces the amount of data required to obtain a confident mitochondrial haplogroup assignment. Author summary: Pangenome graphs are powerful and relatively nascent data structures for representing an entire collection of genomic sequences and their homology. Here we present HaploCart, a tool which leverages the power of pangenomics, in conjunction with maximum-likelihood estimation, to improve human mtDNA haplotype inference on single-source samples (i.e. the sample is not a mixture of multiple contributors, be they human or contaminant). In this context, mapping to many reference genomes at once vastly reduces the Eurocentric bias inherent in contemporary methods, and also improves haplotyping performance at low coverage depths. We show that HaploCart is far more accurate than competing programs on simulated and empirical datasets, and reports clade-level posterior probabilities that accurately reflect confidence in our phylogenetic assignments. Our work can easily be generalized to other haploid markers and suggests that pangenome-based approaches combined with Bayesian methods show promise for improving inference and mitigating ethnicity-related bias in a large class of bioinformatics problems involving sequencing data. [ABSTRACT FROM AUTHOR]

Even when trained under exactly the same conditions outbred male Sprague-Dawley (SD) rats vary in the form of the Pavlovian conditioned approach response (CR) they acquire. The form of the CR (i.e. sign-tracking vs. goal-tracking) predicts to what degree individuals attribute incentive salience to cues associated with food or drugs. However, we have noticed variation in the incidence of these two phenotypes in rats obtained from different vendors. In this study, we quantified sign- and goal-tracking behavior in a reasonably large sample of SD rats obtained from two vendors (Harlan or Charles River), as well as from individual colonies operated by both vendors. Our sample of rats acquired from Harlan had, on average, more sign-trackers than goal-trackers, and vice versa for our sample of rats acquired from Charles River. Furthermore, there were significant differences among colonies of the same vendor. Although it is impossible to rule out environmental variables, SD rats at different vendors and barriers may have reduced phenotypic heterogeneity as a result of genetic variables, such as random genetic drift or population bottlenecks. Consistent with this hypothesis, we identified marked population structure among colonies from Harlan. Therefore, despite sharing the same name, investigators should be aware that important genetic and phenotypic differences exist among SD rats from different vendors or even from different colonies of the same vendor. If used judiciously this can be an asset to experimental design, but it can also be a pitfall for those unaware of the issue. [ABSTRACT FROM AUTHOR]

Next Generation Sequencing Technology has revolutionized our ability to study the contribution of rare genetic variation to heritable traits. However, existing single-marker association tests are underpowered for detecting rare risk variants. A more powerful approach involves pooling methods that combine multiple rare variants from the same gene into a single test statistic. Proposed pooling methods can be limited because they generally assume high-quality genotypes derived from deep-coverage sequencing, which may not be available. In this paper, we consider an intuitive and computationally efficient pooling statistic, the cumulative minor-allele test (CMAT). We assess the performance of the CMAT and other pooling methods on datasets simulated with population genetic models to contain realistic levels of neutral variation. We consider study designs ranging from exon-only to whole-gene analyses that contain noncoding variants. For all study designs, the CMAT achieves power comparable to that of previously proposed methods. We then extend the CMAT to probabilistic genotypes and describe application to low-coverage sequencing and imputation data. We show that augmenting sequence data with imputed samples is a practical method for increasing the power of rare-variant studies. We also provide a method of controlling for confounding variables such as population stratification. Finally, we demonstrate that our method makes it possible to use external imputation templates to analyze rare variants imputed into existing GWAS datasets. As proof of principle, we performed a CMAT analysis of more than 8 million SNPs that we imputed into the GAIN psoriasis dataset by using haplotypes from the 1000 Genomes Project. [ABSTRACT FROM AUTHOR]

The Seychelles magpie‐robin's (SMR) five island populations exhibit some of the lowest recorded levels of genetic diversity among endangered birds, and high levels of inbreeding. These populations collapsed during the 20th century, and the species was listed as Critically Endangered in the IUCN Red List in 1994. An assisted translocation‐for‐recovery program initiated in the 1990s increased the number of mature individuals, resulting in its downlisting to Endangered in 2005. Here, we explore the temporal genomic erosion of the SMR based on a dataset of 201 re‐sequenced whole genomes that span the past ~150 years. Our sample set includes individuals that predate the bottleneck by up to 100 years, as well as individuals from contemporary populations established during the species recovery program. Despite the SMR's recent demographic recovery, our data reveal a marked increase in both the genetic load and realized load in the extant populations when compared to the historical samples. Conservation management may have reduced the intensity of selection by increasing juvenile survival and relaxing intraspecific competition between individuals, resulting in the accumulation of loss‐of‐function mutations (i.e. severely deleterious variants) in the rapidly recovering population. In addition, we found a 3‐fold decrease in genetic diversity between temporal samples. While the low genetic diversity in modern populations may limit the species' adaptability to future environmental changes, future conservation efforts (including IUCN assessments) may also need to assess the threats posed by their high genetic load. Our computer simulations highlight the value of translocations for genetic rescue and show how this could halt genomic erosion in threatened species such as the SMR. [ABSTRACT FROM AUTHOR]

Summary The evolutionary history of the wolf-like canids of the genus Canis has been heavily debated, especially regarding the number of distinct species and their relationships at the population and species level [ 1–6 ]. We assembled a dataset of 48 resequenced genomes spanning all members of the genus Canis except the black-backed and side-striped jackals, encompassing the global diversity of seven extant canid lineages. This includes eight new genomes, including the first resequenced Ethiopian wolf (Canis simensis), one dhole (Cuon alpinus), two East African hunting dogs (Lycaon pictus), two Eurasian golden jackals (Canis aureus), and two Middle Eastern gray wolves (Canis lupus). The relationships between the Ethiopian wolf, African golden wolf, and golden jackal were resolved. We highlight the role of interspecific hybridization in the evolution of this charismatic group. Specifically, we find gene flow between the ancestors of the dhole and African hunting dog and admixture between the gray wolf, coyote (Canis latrans), golden jackal, and African golden wolf. Additionally, we report gene flow from gray and Ethiopian wolves to the African golden wolf, suggesting that the African golden wolf originated through hybridization between these species. Finally, we hypothesize that coyotes and gray wolves carry genetic material derived from a "ghost" basal canid lineage. Graphical Abstract Highlights • Extensive gene flow in the genus Canis , especially among the crown group • Genetic contribution from an unknown canid into the ancestor of the gray wolf and coyote • The African golden wolf possibly a hybrid species, from the gray wolf and Ethiopian wolf • Possible ancient admixture between the dhole and African hunting dog Gopalakrishnan et al. present evidence of pervasive gene flow among species of the genus Canis. In addition to previously known admixture events, they find evidence of gene flow from a "ghost" canid, related to the dhole, into the ancestor of the gray wolf and coyote. Further, they suggest that the African golden wolf is a species of hybrid origin. [ABSTRACT FROM AUTHOR]

Ancestral Coast Salish societies in the Pacific Northwest kept long-haired “woolly dogs” that were bred and cared for over millennia. However, the dog wool–weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from “Mutton,” collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance. [ABSTRACT FROM AUTHOR]

The application of high‐throughput sequencing‐based approaches to DNA extracted from environmental samples such as gut contents and faeces has become a popular tool for studying dietary habits of animals. Due to the high resolution and prey detection capacity they provide, both metabarcoding and shotgun sequencing are increasingly used to address ecological questions grounded in dietary relationships. Despite their great promise in this context, recent research has unveiled how a wealth of biological (related to the study system) and technical (related to the methodology) factors can distort the signal of taxonomic composition and diversity. Here, we review these studies in the light of high‐throughput sequencing‐based assessment of trophic interactions. We address how the study design can account for distortion factors, and how acknowledging limitations and biases inherent to sequencing‐based diet analyses are essential for obtaining reliable results, thus drawing appropriate conclusions. Furthermore, we suggest strategies to minimize the effect of distortion factors, measures to increase reproducibility, replicability and comparability of studies, and options to scale up DNA sequencing‐based diet analyses. In doing so, we aim to aid end‐users in designing reliable diet studies by informing them about the complexity and limitations of DNA sequencing‐based diet analyses, and encourage researchers to create and improve tools that will eventually drive this field to its maturity. [ABSTRACT FROM AUTHOR]

The island of St Helena played a crucial role in the suppression of the transatlantic slave trade. Strategically located in the middle of the South Atlantic, it served as a staging post for the Royal Navy and reception point for enslaved Africans who had been "liberated" from slave ships intercepted by the British. In total, St Helena received approximately 27,000 liberated Africans between 1840 and 1867. Written sources suggest that the majority of these individuals came from West Central Africa, but their precise origins are unknown. Here, we report the results of ancient DNA analyses that we conducted as part of a wider effort to commemorate St Helena's liberated Africans and to restore knowledge of their lives and experiences. We generated partial genomes (0.1–0.5×) for 20 individuals whose remains had been recovered during archaeological excavations on the island. We compared their genomes with genotype data for over 3,000 present-day individuals from 90 populations across sub-Saharan Africa and conclude that the individuals most likely originated from different source populations within the general area between northern Angola and Gabon. We also find that the majority (17/20) of the individuals were male, supporting a well-documented sex bias in the latter phase of the transatlantic slave trade. The study expands our understanding of St Helena's liberated African community and illustrates how ancient DNA analyses can be used to investigate the origins and identities of individuals whose lives were bound up in the story of slavery and its abolition. During the mid-19th century, around 27,000 "liberated Africans" were brought to St Helena island as part of the Royal Navy's efforts to suppress the transatlantic trade in enslaved Africans. Ancient DNA analyses, carried out on behalf of the community on St Helena, now shed light on their origins and identities. [ABSTRACT FROM AUTHOR]

The Caribbean was one of the last parts of the Americas to be settled by humans, but how and when the islands were first occupied remains a matter of debate. Ancient DNA can help answering these questions, but the work has been hampered by poor DNA preservation. We report the genome sequence of a 1,000-year-old Lucayan Taino individual recovered from the site of Preacher's Cave in the Bahamas. We sequenced her genome to 12.4-fold coverage and show that she is genetically most closely related to present-day Arawakan speakers from northern South America, suggesting that the ancestors of the Lucayans originated there. Further, we find no evidence for recent inbreeding or isolation in the ancient genome, suggesting that the Lucayans had a relatively large effective population size. Finally, we show that the native American components in some present-day Caribbean genomes are closely related to the ancient Taino, demonstrating an element of continuity between precontact populations and presentday Latino populations in the Caribbean. [ABSTRACT FROM AUTHOR]

Motivation Machine learning (ML) methods are motivated by the need to automate information extraction from large datasets in order to support human users in data-driven tasks. This is an attractive approach for integrative joint analysis of vast amounts of omics data produced in next generation sequencing and other -omics assays. A systematic assessment of the current literature can help to identify key trends and potential gaps in methodology and applications. We surveyed the literature on ML multi-omic data integration and quantitatively explored the goals, techniques and data involved in this field. We were particularly interested in examining how researchers use ML to deal with the volume and complexity of these datasets. Results Our main finding is that the methods used are those that address the challenges of datasets with few samples and many features. Dimensionality reduction methods are used to reduce the feature count alongside models that can also appropriately handle relatively few samples. Popular techniques include autoencoders, random forests and support vector machines. We also found that the field is heavily influenced by the use of The Cancer Genome Atlas dataset, which is accessible and contains many diverse experiments. Availability and implementation All data and processing scripts are available at this GitLab repository: https://gitlab.com/polavieja%5flab/ml%5fmulti-omics%5freview/ or in Zenodo: https://doi.org/10.5281/zenodo.7361807. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

The vertebrate cranium is a prime example of the high evolvability of complex traits. While evidence of genes and developmental pathways underlying craniofacial shape determination is accumulating, we are still far from understanding how such variation at the genetic level is translated into craniofacial shape variation. Here we used 3D geometric morphometrics to map genes involved in shape determination in a population of outbred mice (Carworth Farms White, or CFW). We defined shape traits via principal component analysis of 3D skull and mandible measurements. We mapped genetic loci associated with shape traits at ~80,000 candidate single nucleotide polymorphisms in ~700 male mice. We found that craniofacial shape and size are highly heritable, polygenic traits. Despite the polygenic nature of the traits, we identified 17 loci that explain variation in skull shape, and 8 loci associated with variation in mandible shape. Together, the associated variants account for 11.4% of skull and 4.4% of mandible shape variation, however, the total additive genetic variance associated with phenotypic variation was estimated in ~45%. Candidate genes within the associated loci have known roles in craniofacial development; this includes 6 transcription factors and several regulators of bone developmental pathways. One gene, Mn1, has an unusually large effect on shape variation in our study. A knockout of this gene was previously shown to affect negatively the development of membranous bones of the cranial skeleton, and evolutionary analysis shows that the gene has arisen at the base of the bony vertebrates (Eutelostomi), where the ossified head first appeared. Therefore, Mn1 emerges as a key gene for both skull formation and within-population shape variation. Our study shows that it is possible to identify important developmental genes through genome-wide mapping of high-dimensional shape features in an outbred population. [ABSTRACT FROM AUTHOR]

The article highlights that the wide-scale introduction of exotic species to novel ranges around the world can be largely attributed to the 19th century colonial activities of Europeans and to escalating global trade activities since the 20th century. It also discusses that many more species are introduced to novel ranges than become invasive.

Snake venoms represent a danger to human health, but also a gold mine of bioactive proteins that can be harnessed for drug discovery purposes. The evolution of snakes and their venom has been studied for decades, particularly via traditional morphological and basic genetic methods alongside venom proteomics. However, while the field of genomics has matured rapidly over the past 2 decades, owing to the development of next-generation sequencing technologies, snake genomics remains in its infancy. Here, we provide an overview of the state of the art in snake genomics and discuss its potential implications for studying venom evolution and toxinology. On the basis of current knowledge, gene duplication and positive selection are key mechanisms in the neofunctionalization of snake venom proteins. This makes snake venoms important evolutionary drivers that explain the remarkable venom diversification and adaptive variation observed in these reptiles. Gene duplication and neofunctionalization have also generated a large number of repeat sequences in snake genomes that pose a significant challenge to DNA sequencing, resulting in the need for substantial computational resources and longer sequencing read length for high-quality genome assembly. Fortunately, owing to constantly improving sequencing technologies and computational tools, we are now able to explore the molecular mechanisms of snake venom evolution in unprecedented detail. Such novel insights have the potential to affect the design and development of antivenoms and possibly other drugs, as well as provide new fundamental knowledge on snake biology and evolution. [ABSTRACT FROM AUTHOR]

Although today the forest cover is continuous in Central Africa, this may have not always been the case, as the scarce fossil record in this region suggests that arid conditions might have significantly reduced tree density during the ice ages. Our aim was to investigate whether the dry ice age periods left a genetic signature on tree species that can be used to infer the date of the past fragmentation of the rainforest. We sequenced reduced representation libraries of 182 samples representing five widespread legume trees and seven outgroups. Phylogenetic analyses identified an early divergent lineage for all species in West Africa (Upper Guinea) and two clades in Central Africa: Lower Guinea-North and Lower Guinea-South. As the structure separating the Northern and Southern clades--congruent across species--cannot be explained by geographic barriers, we tested other hypotheses with demographic model testing using δαδ?. The best estimates indicate that the two clades split between the Upper Pliocene and the Pleistocene, a date compatible with forest fragmentation driven by ice age climatic oscillations. Furthermore, we found remarkably older split dates for the shade-tolerant tree species with nonassisted seed dispersal than for light-demanding species with longdistance wind-dispersed seeds. Different recolonization abilities after recurrent cycles of forest fragmentation seem to explain why species with long-distance dispersal show more recent genetic admixture between the two clades than species with limited seed dispersal. Despite their old history, our results depict the African rainforests as a dynamic biome where tree species have expanded relatively recently after the last glaciation. [ABSTRACT FROM AUTHOR]

Several Arctic marine mammal species are predicted to be negatively impacted by rapid sea ice loss associated with ongoing ocean warming. However, consequences for Arctic whales remain uncertain. To investigate how Arctic whales responded to past climatic fluctuations, we analysed 206 mitochondrial genomes from beluga whales (Delphinapterus leucas) sampled across their circumpolar range, and four nuclear genomes, covering both the Atlantic and the Pacific Arctic region. We found four well‐differentiated mitochondrial lineages, which were established before the onset of the last glacial expansion ~110 thousand years ago. Our findings suggested these lineages diverged in allopatry, reflecting isolation of populations during glacial periods when the Arctic sea‐shelf was covered by multiyear sea ice. Subsequent population expansion and secondary contact between the Atlantic and Pacific Oceans shaped the current geographic distribution of lineages, and may have facilitated mitochondrial introgression. Our demographic reconstructions based on both mitochondrial and nuclear genomes showed markedly lower population sizes during the Last Glacial Maximum (LGM) compared to the preceding Eemian and current Holocene interglacial periods. Habitat modelling similarly revealed less suitable habitat during the LGM (glacial) than at present (interglacial). Together, our findings suggested the association between climate, population size, and available habitat in belugas. Forecasts for year 2100 showed that beluga habitat will decrease and shift northwards as oceans continue to warm, putatively leading to population declines in some beluga populations. Finally, we identified vulnerable populations which, if extirpated as a consequence of ocean warming, will lead to a substantial decline of species‐wide haplotype diversity. [ABSTRACT FROM AUTHOR]

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record. [ABSTRACT FROM AUTHOR]

The heterogeneous stock (HS) is an outbred rat population derived from eight inbred rat strains. HS rats are ideally suited for genome wide association studies; however, only a few genotyping microarrays have ever been designed for rats and none of them are currently in production. To address the need for an efficient and cost effective method of genotyping HS rats, we have adapted genotype-by-sequencing (GBS) to obtain genotype information at large numbers of single nucleotide polymorphisms (SNPs). In this paper, we have outlined the laboratory and computational steps we took to optimize double digest genotype-bysequencing (ddGBS) for use in rats. We evaluated multiple existing computational tools and explain the workflow we have used to call and impute over 3.7 million SNPs. We have also compared various rat genetic maps, which are necessary for imputation, including a recently developed map specific to the HS. Using our approach, we obtained concordance rates of 99% with data obtained using data from a genotyping array. The principles and computational pipeline that we describe could easily be adapted for use in other species for which reliable reference genome sets are available. [ABSTRACT FROM AUTHOR]

The Arctic is warming at an unprecedented rate, with unknown consequences for endemic fauna. However, Earth has experienced severe climatic oscillations in the past, and understanding how species responded to them might provide insight into their resilience to near-future climatic predictions. Little is known about the responses of Arctic marine mammals to past climatic shifts, but narwhals (Monodonmonoceros) are considered one of the endemic Arctic species most vulnerable to environmental change. Here, we analyse 121 complete mitochondrial genomes from narwhals sampled across their range and use the min combination with species distribution models to elucidate the influence of past and ongoing climatic shifts on their population structure and demographic history. We find lowlevels of genetic diversity and limited geographic structuring of genetic clades. We show that narwhals experienced a long-term low effective population size, which increased after the Last Glacial Maximum, when the amount of suitable habitat expanded. Similar post-glacial habitat release has been a key driver of population size expansion of other polarmarine predators. Our analyses indicate that habitat availability has been critical to the success of narwhals, raising concerns for their fate in an increasingly warming Arctic. [ABSTRACT FROM AUTHOR]

The Arctic is warming at an unprecedented rate, with unknown consequences for endemic fauna. However, Earth has experienced severe climatic oscillations in the past, and understanding how species responded to them might provide insight into their resilience to near-future climatic predictions. Little is known about the responses of Arctic marine mammals to past climatic shifts, but narwhals (Monodon monoceros) are considered one of the endemic Arctic species most vulnerable to environmental change. Here, we analyse 121 complete mitochondrial genomes from narwhals sampled across their range and use them in combination with species distribution models to elucidate the influence of past and ongoing climatic shifts on their population structure and demographic history. We find low levels of genetic diversity and limited geographic structuring of genetic clades. We show that narwhals experienced a long-term low effective population size, which increased after the Last Glacial Maximum, when the amount of suitable habitat expanded. Similar post-glacial habitat release has been a key driver of population size expansion of other polar marine predators. Our analyses indicate that habitat availability has been critical to the success of narwhals, raising concerns for their fate in an increasingly warming Arctic. [ABSTRACT FROM AUTHOR]

Domestic dogs have been central to life in the North American Arctic for millennia. The ancestors of the Inuit were the first to introduce the widespread usage of dog sledge transportation technology to the Americas, but whether the Inuit adopted local Palaeo-Inuit dogs or introduced a new dog population to the region remains unknown. To test these hypotheses, we generated mitochondrial DNA and geometric morphometric data of skull and dental elements from a total of 922 North American Arctic dogs and wolves spanning over 4500 years. Our analyses revealed that dogs from Inuit sites dating from 2000 BP possess morphological and genetic signatures that distinguish them from earlier Palaeo-Inuit dogs, and identified a novel mitochondrial clade in eastern Siberia and Alaska. The genetic legacy of these Inuit dogs survives today in modern Arctic sledge dogs despite phenotypic differences between archaeological and modern Arctic dogs. Together, our data reveal that Inuit dogs derive from a secondary pre-contact migration of dogs distinct from Palaeo-Inuit dogs, and probably aided the Inuit expansion across the North American Arctic beginning around 1000 BP. [ABSTRACT FROM AUTHOR]

Environmental variation across the range of wild species can lead to local adaptations. The Baltic Sea was formed when the Fenno-Scandian ice sheet retreated around 12 thousand years ago, creating a new brackish water habitat colonised by both marine and freshwater fish species. The European perch (Perca fluviatilis) is a predatory freshwater fish with a large geographical distribution across Eurasia, where it inhabits a wide range of environmental niches. In the Baltic Sea region it has even developed a specialised brackish water perch variant that can tolerate environmental salinity levels, which are lethal to freshwater perch. However, very little is known about the underlying mechanisms facilitating the colonisation and adaptation of perch to the Baltic Sea. Here, we use Genotyping-By-Sequencing data from six freshwater and six brackish water localities to disclose the evolutionary relationship between freshwater and brackish water perch. Our results show that the brackish water perch occurs in multiple distinct genetic clusters. We find that gene flow between brackish water perch with full access to the sea likely led to lower levels of differentiation and higher diversity than in freshwater perch. Selection analyses suggest that genomic adaptation played a role in the colonisation of the Baltic Sea and that the top three regions under selection harbour salinity tolerance genes. We complete by discussing the implications of our findings for management of brackish water perch in the western Baltic sea. [Display omitted] • GBS data from 12 perch populations, six with brackish and six with freshwater origin. • Brackish water populations were found in all three major genetic clades. • Top three regions under selection harboured salinity tolerance genes. [ABSTRACT FROM AUTHOR]

The article presents a study in which DNA sequencing was used to determine the origin and mode of domestication for dogs in the Americas.

Abstract: The interaction between agricultural production and wildlife can shape, and even condition, the functioning of both systems. In this study, we i) explored the degree to which a widespread European bat, namely the common bent‐wing bat Miniopterus schreibersii, consumes crop‐damaging insects at a continental scale, and ii) tested whether its dietary niche is shaped by the extension and type of agricultural fields. We employed a dual‐primer DNA metabarcoding approach to characterize arthropod 16S and COI DNA sequences within bat faecal pellets collected across 16 Southern European localities, to first characterize the bat species’ dietary niche, second measure the incidence of agricultural pests across their ranges and third assess whether geographical dietary variation responds to climatic, landscape diversity, agriculture type and vegetation productivity factors. We detected 12 arthropod orders, among which lepidopterans were predominant. We identified >200 species, 44 of which are known to cause agricultural damage. Pest species were detected at all but one sampling site and in 94% of the analysed samples. Furthermore, the dietary diversity of M. schreibersii exhibited a negative linear relation with the area of intensive agricultural fields, thus suggesting crops restrict the dietary niche of bats to prey taxa associated with agricultural production within their foraging range. Overall, our results imply that M. schreibersii might be a valuable asset for biological pest suppression in a variety of agricultural productions and highlight the dynamic interplay between wildlife and agricultural systems. [ABSTRACT FROM AUTHOR]

Summary The complex evolutionary history of maize ( Zea mays L. ssp. mays ) has been clarified with genomic-level data from modern landraces and wild teosinte grasses [ 1, 2 ], augmenting archaeological findings that suggest domestication occurred between 10,000 and 6,250 years ago in southern Mexico [ 3, 4 ]. Maize rapidly evolved under human selection, leading to conspicuous phenotypic transformations, as well as adaptations to varied environments [ 5 ]. Still, many questions about the domestication process remain unanswered because modern specimens do not represent the full range of past diversity due to abandonment of unproductive lineages, genetic drift, on-going natural selection, and recent breeding activity. To more fully understand the history and spread of maize, we characterized the draft genome of a 5,310-year-old archaeological cob excavated in the Tehuacan Valley of Mexico. We compare this ancient sample against a reference panel of modern landraces and teosinte grasses using D statistics, model-based clustering algorithms, and multidimensional scaling analyses, demonstrating the specimen derives from the same source population that gave rise to modern maize. We find that 5,310 years ago, maize in the Tehuacan Valley was on the whole genetically closer to modern maize than to its wild counterpart. However, many genes associated with key domestication traits existed in the ancestral state, sharply contrasting with the ubiquity of derived alleles in living landraces. These findings suggest much of the evolution during domestication may have been gradual and encourage further paleogenomic research to address provocative questions about the world’s most produced cereal. [ABSTRACT FROM AUTHOR]

The Anthropocene is witnessing a loss of biodiversity, with well-documented declines in the diversity of ecosystems and species. For intraspecific genetic diversity, however, we lack even basic knowledge on its global distribution. We georeferenced 92,801 mitochondrial sequences for >4500 species of terrestrial mammals and amphibians, and found that genetic diversity is 27% higher in the tropics than in nontropical regions. Overall, habitats that are more affected by humans hold less genetic diversity than wilder regions, although results for mammals are sensitive to choice of genetic locus. Our study associates geographic coordinates with publicly available genetic sequences at a massive scale, yielding an opportunity to investigate both the drivers of this component of biodiversity and the genetic consequences of the anthropogenic modification of nature. [ABSTRACT FROM AUTHOR]

Archaeological consideration of maritime connectivity has ranged from a biogeographical perspective that considers the sea as a barrier to a view of seaways as ancient highways that facilitate exchange. Our results illustrate the former. We report three Late Neolithic human genomes from the Mediterranean island of Malta that are markedly enriched for runs of homozygosity, indicating inbreeding in their ancestry and an effective population size of only hundreds, a striking illustration of maritime isolation in this agricultural society. In the Late Neolithic, communities across mainland Europe experienced a resurgence of hunter-gatherer ancestry, pointing toward the persistence of different ancestral strands that subsequently admixed. This is absent in the Maltese genomes, giving a further indication of their genomic insularity. Imputation of genome-wide genotypes in our new and 258 published ancient individuals allowed shared identity-by-descent segment analysis, giving a fine-grained genetic geography of Neolithic Europe. This highlights the differentiating effects of seafaring Mediterranean expansion and also island colonization, including that of Ireland, Britain, and Orkney. These maritime effects contrast profoundly with a lack of migratory barriers in the establishment of Central European farming populations from Anatolia and the Balkans. [Display omitted] • Three inbred genomes from Malta, dated around 2500 BC • As in moderns, the genetic structure of Neolithic genomes is shaped by geography • Genomic insularity of island Neolithic populations • A marked distinction between the Danubian and Mediterranean farming expansion routes Using high-coverage genomes from ancient Maltese, Ariano et al. show that they had signals of both recent and more distant inbreeding, indicating small population size. Using diploid genome-wide data, the authors explore the genetic geography of Neolithic Europe which, echoing modern patterns, is shaped by physical topography, especially its seascapes. [ABSTRACT FROM AUTHOR]

Three principal methods are under discussion as possible pathways to "true" de-extinction; i.e., back-breeding, cloning, and genetic engineering. 1,2 Of these, while the latter approach is most likely to apply to the largest number of extinct species, its potential is constrained by the degree to which the extinct species genome can be reconstructed. We explore this question using the extinct Christmas Island rat (Rattus macleari) as a model, an endemic rat species that was driven extinct between 1898 and 1908. 3–5 We first re-sequenced its genome to an average of >60× coverage, then mapped it to the reference genomes of different Rattus species. We then explored how evolutionary divergence from the extant reference genome affected the fraction of the Christmas Island rat genome that could be recovered. Our analyses show that even when the extremely high-quality Norway brown rat (R. norvegicus) is used as a reference, nearly 5% of the genome sequence is unrecoverable, with 1,661 genes recovered at lower than 90% completeness, and 26 completely absent. Furthermore, we find the distribution of regions affected is not random, but for example, if 90% completeness is used as the cutoff, genes related to immune response and olfaction are excessively affected. Ultimately, our approach demonstrates the importance of applying similar analyses to candidates for de-extinction through genome editing in order to provide critical baseline information about how representative the edited form would be of the extinct species. • Evolutionary divergence limits the completeness of extinct species genomes • The extinct Christmas Island rat was re-sequenced to ca. 60× coverage • Nevertheless, 4.85% of the Norway brown rat genome remains absent after mapping • Absences are not random; immune response and olfaction are excessively affected Lin et al. explore how evolutionary divergence constrains the potential of de-extinction, using the Christmas Island rat as a model. Although 95% of its genome is recovered when re-sequenced at high depth, regions that remain unmapped to the reference likely have significant consequences for any attempt at de-extinction using genome editing. [ABSTRACT FROM AUTHOR]

The Sardinian dhole (Cynotherium sardous) 1 was an iconic and unique canid species that was endemic to Sardinia and Corsica until it became extinct at the end of the Late Pleistocene. 2–5 Given its peculiar dental morphology, small body size, and high level of endemism, several extant canids have been proposed as possible relatives of the Sardinian dhole, including the Asian dhole and African hunting dog ancestor. 3,6–9 Morphometric analyses 3,6,8–12 have failed to clarify the evolutionary relationship with other canids.We sequenced the genome of a ca -21,100-year-old Sardinian dhole in order to understand its genomic history and clarify its phylogenetic position. We found that it represents a separate taxon from all other living canids from Eurasia, Africa, and North America, and that the Sardinian dhole lineage diverged from the Asian dhole ca 885 ka. We additionally detected historical gene flow between the Sardinian and Asian dhole lineages, which ended approximately 500-300 ka, when the land bridge between Sardinia and mainland Italy was already broken, severing their population connectivity. Our sample showed low genome-wide diversity compared to other extant canids—probably a result of the long-term isolation—that could have contributed to the subsequent extinction of the Sardinian dhole. • The Sardinian dhole lineage diverged from the Asian dholes around 885 ka • Post-divergence gene flow between the dhole lineages ended between 560 and 310 ka • Our sample also showed a reduced genome-wide diversity • The gene flow between Lycaon and the dholes' ancestor ended around 1.05–0.83 Ma Ciucani et al. sequence the genome of a 21,100-year-old Sardinian dhole. The sample represents a different lineage from the current Asian dholes and split from them ca 885 ka. Post-divergence gene flow between the two lineages ended later— ca 560–310 ka—followed by a stable but long-term population decline and extinction of the Sardinian dhole. [ABSTRACT FROM AUTHOR]

Homotherium was a genus of large-bodied scimitar-toothed cats, morphologically distinct from any extant felid species, that went extinct at the end of the Pleistocene [ 1–4 ]. They possessed large, saber-form serrated canine teeth, powerful forelimbs, a sloping back, and an enlarged optic bulb, all of which were key characteristics for predation on Pleistocene megafauna [ 5 ]. Previous mitochondrial DNA phylogenies suggested that it was a highly divergent sister lineage to all extant cat species [ 6–8 ]. However, mitochondrial phylogenies can be misled by hybridization [ 9 ], incomplete lineage sorting (ILS), or sex-biased dispersal patterns [ 10 ], which might be especially relevant for Homotherium since widespread mito-nuclear discrepancies have been uncovered in modern cats [ 10 ]. To examine the evolutionary history of Homotherium , we generated a ∼7x nuclear genome and a ∼38x exome from H. latidens using shotgun and target-capture sequencing approaches. Phylogenetic analyses reveal Homotherium as highly divergent (∼22.5 Ma) from living cat species, with no detectable signs of gene flow. Comparative genomic analyses found signatures of positive selection in several genes, including those involved in vision, cognitive function, and energy consumption, putatively consistent with diurnal activity, well-developed social behavior, and cursorial hunting [ 5 ]. Finally, we uncover relatively high levels of genetic diversity, suggesting that Homotherium may have been more abundant than the limited fossil record suggests [ 3 , 4 , 11–14 ]. Our findings complement and extend previous inferences from both the fossil record and initial molecular studies, enhancing our understanding of the evolution and ecology of this remarkable lineage. • Nuclear genome and exome analyses of extinct scimitar-toothed cat, Homotherium latidens • Homotherium was a highly divergent lineage from all living cat species (∼22.5 Ma) • Genetic adaptations to cursorial and diurnal hunting behaviors • Relatively high levels of genetic diversity in this individual Here, Barnett et al. sequence the nuclear genome of Homotherium latidens through a combination of shotgun and target-capture approaches. Analyses confirm Homotherium to be a highly divergent lineage from all living cat species (∼22.5 Ma) and reveal genes under selection putatively related to a cursorial and diurnal hunting behavior. [ABSTRACT FROM AUTHOR]