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    University - Scholar Department: Biology Position: Postdoctoral Scholar

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  • Mail Code: 5020

All Publications

  • Rapid evolutionary diversification of the flamenco locus across simulans clade Drosophila species. PLoS genetics Signor, S., Vedanayagam, J., Kim, B. Y., Wierzbicki, F., Kofler, R., Lai, E. C. 2023; 19 (8): e1010914

    Abstract

    Suppression of transposable elements (TEs) is paramount to maintain genomic integrity and organismal fitness. In D. melanogaster, the flamenco locus is a master suppressor of TEs, preventing the mobilization of certain endogenous retrovirus-like TEs from somatic ovarian support cells to the germline. It is transcribed by Pol II as a long (100s of kb), single-stranded, primary transcript, and metabolized into ~24-32 nt Piwi-interacting RNAs (piRNAs) that target active TEs via antisense complementarity. flamenco is thought to operate as a trap, owing to its high content of recent horizontally transferred TEs that are enriched in antisense orientation. Using newly-generated long read genome data, which is critical for accurate assembly of repetitive sequences, we find that flamenco has undergone radical transformations in sequence content and even copy number across simulans clade Drosophilid species. Drosophila simulans flamenco has duplicated and diverged, and neither copy exhibits synteny with D. melanogaster beyond the core promoter. Moreover, flamenco organization is highly variable across D. simulans individuals. Next, we find that D. simulans and D. mauritiana flamenco display signatures of a dual-stranded cluster, with ping-pong signals in the testis and/or embryo. This is accompanied by increased copy numbers of germline TEs, consistent with these regions operating as functional dual-stranded clusters. Overall, the physical and functional diversity of flamenco orthologs is testament to the extremely dynamic consequences of TE arms races on genome organization, not only amongst highly related species, but even amongst individuals.

    View details for DOI 10.1371/journal.pgen.1010914

    View details for PubMedID 37643184

  • GENOME REPORT: Chromosome-scale genome assembly of the African spiny mouse (Acomys cahirinus). G3 (Bethesda, Md.) Nguyen, E. D., Fard, V. N., Kim, B. Y., Collins, S., Galey, M., Nelson, B. R., Wakenight, P., Gable, S. M., McKenna, A., Bammler, T. K., MacDonald, J., Okamura, D. M., Shendure, J., Beier, D. R., Ramirez, J. M., Majesky, M. W., Millen, K. J., Tollis, M., Miller, D. E. 2023

    Abstract

    There is increasing interest in the African spiny mouse (Acomys cahirinus) as a model organism because of its ability for regeneration of tissue after injury in skin, muscle, and internal organs such as the kidneys. A high-quality reference genome is needed to better understand these regenerative properties at the molecular level. Here, we present an improved reference genome for A. cahirinus generated from long Nanopore sequencing reads. We confirm the quality of our annotations using RNA sequencing data from four different tissues. Our genome is of higher contiguity and quality than previously reported genomes from this species and will facilitate ongoing efforts to better understand the regenerative properties of this organism.

    View details for DOI 10.1093/g3journal/jkad177

    View details for PubMedID 37552705

  • Decoupled evolution of the Sex Peptide gene family and Sex Peptide Receptor in Drosophilidae. bioRxiv : the preprint server for biology Hopkins, B. R., Angus-Henry, A., Kim, B. Y., Carlisle, J. A., Thompson, A., Kopp, A. 2023

    Abstract

    Across internally fertilising species, males transfer proteins in their ejaculate that trigger wide-ranging changes in female behaviour and physiology. Much theory has been developed to explore the drivers of ejaculate protein evolution. The accelerating availability of high-quality genomes now allows us to test how these proteins are evolving at fine taxonomic scales. Here, we use genomes from 199, mostly drosophilid, species to chart the evolutionary history of Sex Peptide (SP), a potent regulator of female post-mating responses. We infer that SP has followed markedly different evolutionary trajectories in different lineages. Outside of the Sophophora-Lordiphosa radiation, SP exists largely as a single copy gene that has been independently lost in several lineages. In contrast, within the Sophophora-Lordiphosa radiation SP has repeatedly and independently duplicated. Up to seven copies, collectively displaying extensive variation in sequence, are present in some species. We use cross-species RNA-seq data to provide evidence that this lineage-specific burst in evolutionary activity did not follow a significant shift in the sex- or tissue-specificity of SP's expression. We also document considerable interspecific variation in accessory gland microcarriers that appears to be independent of SP presence or sequence. We end by showing that the mode of SP's evolution is decoupled from that of its receptor, SPR, in which we detect no evidence of correlated diversifying selection in its coding sequence. Collectively, our work describes the divergent evolutionary trajectories that an apparently novel drosophilid gene has followed in different branches of the phylogeny and finds a surprisingly weak coevolutionary signal between a supposedly sexually antagonistic protein and its receptor.

    View details for DOI 10.1101/2023.06.29.547128

    View details for PubMedID 37425821

    View details for PubMedCentralID PMC10327216

  • Evolution of chemosensory and detoxification gene families across herbivorous Drosophilidae. G3 (Bethesda, Md.) Peláez, J. N., Gloss, A. D., Goldman-Huertas, B., Kim, B., Lapoint, R. T., Pimentel-Solorio, G., Verster, K. I., Aguilar, J. M., Nelson Dittrich, A. C., Singhal, M., Suzuki, H. C., Matsunaga, T., Armstrong, E. E., Charboneau, J. L., Groen, S. C., Hembry, D. H., Ochoa, C. J., O'Connor, T. K., Prost, S., Zaaijer, S., Nabity, P. D., Wang, J., Rodas, E., Liang, I., Whiteman, N. K. 2023

    Abstract

    Herbivorous insects are exceptionally diverse, accounting for a quarter of all known eukaryotic species, but the genomic basis of adaptations that enabled this dietary transition remains poorly understood. Many studies have suggested that expansions and contractions of chemosensory and detoxification gene families - genes directly mediating interactions with plant chemical defenses - underlie successful plant colonization. However, this hypothesis has been challenging to test because the origins of herbivory in many insect lineages are ancient (>150 million years ago [mya]), obscuring genomic evolutionary patterns. Here, we characterized chemosensory and detoxification gene family evolution across Scaptomyza, a genus nested within Drosophila that includes a recently derived (<15 mya) herbivore lineage of mustard (Brassicales) specialists and carnation (Caryophyllaceae) specialists, and several non-herbivorous species. Comparative genomic analyses revealed that herbivorous Scaptomyza have among the smallest chemosensory and detoxification gene repertoires across 12 drosophilid species surveyed. Rates of gene turnover averaged across the herbivore clade were significantly higher than background rates in over half of the surveyed gene families. However, gene turnover was more limited along the ancestral herbivore branch, with only gustatory receptors and odorant binding proteins experiencing strong losses. The genes most significantly impacted by gene loss, duplication, or changes in selective constraint were those involved in detecting compounds associated with feeding on living plants (bitter or electrophilic phytotoxins) or their ancestral diet (fermenting plant volatiles). These results provide insight into the molecular and evolutionary mechanisms of plant-feeding adaptations and highlight gene candidates that have also been linked to other dietary transitions in Drosophila.

    View details for DOI 10.1093/g3journal/jkad133

    View details for PubMedID 37317982

  • GENOME REPORT: Chromosome-scale genome assembly of the African spiny mouse ( Acomys cahirinus ). bioRxiv : the preprint server for biology Nguyen, E. D., Fard, V. N., Kim, B. Y., Collins, S., Galey, M., Nelson, B. R., Wakenight, P., Gable, S. M., McKenna, A., Bammler, T. K., MacDonald, J., Okamura, D. M., Shendure, J., Beier, D. R., Ramirez, J. M., Majesky, M. W., Millen, K. J., Tollis, M., Miller, D. E. 2023

    Abstract

    There is increasing interest in the African spiny mouse ( Acomys cahirinus ) as a model organism because of its ability for regeneration of tissue after injury in skin, muscle, and internal organs such as the kidneys. A high-quality reference genome is needed to better understand these regenerative properties at the molecular level. Here, we present an improved reference genome for A. cahirinus generated from long Nanopore sequencing reads. We confirm the quality of our annotations using RNA sequencing data from four different tissues. Our genome is of higher contiguity and quality than previously reported genomes from this species and will facilitate ongoing efforts to better understand the regenerative properties of this organism.

    View details for DOI 10.1101/2023.04.03.535372

    View details for PubMedID 37066261

    View details for PubMedCentralID PMC10103962

  • Evolution of chemosensory and detoxification gene families across herbivorous Drosophilidae. bioRxiv : the preprint server for biology Pelaez, J. N., Gloss, A. D., Goldman-Huertas, B., Kim, B., Lapoint, R. T., Pimentel-Solorio, G., Verster, K. I., Aguilar, J. M., Dittrich, A. C., Singhal, M., Suzuki, H. C., Matsunaga, T., Armstrong, E. E., Charboneau, J. L., Groen, S. C., Hembry, D. H., Ochoa, C. J., O'Connor, T. K., Prost, S., Zaaijer, S., Nabity, P. D., Wang, J., Rodas, E., Liang, I., Whiteman, N. K. 2023

    Abstract

    Herbivorous insects are exceptionally diverse, accounting for a quarter of all known eukaryotic species, but the genetic basis of adaptations that enabled this dietary transition remains poorly understood. Many studies have suggested that expansions and contractions of chemosensory and detoxification gene families - genes directly mediating interactions with plant chemical defenses - underlie successful plant colonization. However, this hypothesis has been challenging to test because the origins of herbivory in many lineages are ancient (>150 million years ago [mya]), obscuring genomic evolutionary patterns. Here, we characterized chemosensory and detoxification gene family evolution across Scaptomyza, a genus nested within Drosophila that includes a recently derived (<15 mya) herbivore lineage of mustard (Brassicales) specialists and carnation (Caryophyllaceae) specialists, and several non-herbivorous species. Comparative genomic analyses revealed that herbivorous Scaptomyza have among the smallest chemosensory and detoxification gene repertoires across 12 drosophilid species surveyed. Rates of gene turnover averaged across the herbivore clade were significantly higher than background rates in over half of the surveyed gene families. However, gene turnover was more limited along the ancestral herbivore branch, with only gustatory receptors and odorant binding proteins experiencing strong losses. The genes most significantly impacted by gene loss, duplication, or changes in selective constraint were those involved in detecting compounds associated with feeding on plants (bitter or electrophilic phytotoxins) or their ancestral diet (yeast and fruit volatiles). These results provide insight into the molecular and evolutionary mechanisms of plant-feeding adaptations and highlight strong gene candidates that have also been linked to other dietary transitions in Drosophila .

    View details for DOI 10.1101/2023.03.16.532987

    View details for PubMedID 36993186

    View details for PubMedCentralID PMC10055167

  • Antigenic diversity in malaria parasites is maintained on extrachromosomal DNA. bioRxiv : the preprint server for biology Ebel, E. R., Kim, B. Y., McDew-White, M., Egan, E. S., Anderson, T. J., Petrov, D. A. 2023

    Abstract

    Sequence variation among antigenic var genes enables Plasmodium falciparum malaria parasites to evade host immunity. Using long sequence reads from haploid clones from a mutation accumulation experiment, we detect var diversity inconsistent with simple chromosomal inheritance. We discover putatively circular DNA that is strongly enriched for var genes, which exist in multiple alleles per locus separated by recombination and indel events. Extrachromosomal DNA likely contributes to rapid antigenic diversification in P. falciparum .

    View details for DOI 10.1101/2023.02.02.526885

    View details for PubMedID 36778235

  • MaLAdapt reveals novel targets of adaptive introgression from Neanderthals and Denisovans in worldwide human populations. Molecular biology and evolution Zhang, X., Kim, B., Singh, A., Sankararaman, S., Durvasula, A., Lohmueller, K. E. 2023

    Abstract

    Adaptive introgression (AI) facilitates local adaptation in a wide range of species. Many state-of-the-art methods detect AI with ad-hoc approaches that identify summary statistic outliers or intersect scans for positive selection with scans for introgressed genomic regions. Although widely used, approaches intersecting outliers are vulnerable to a high false-negative rate as the power of different methods varies, especially for complex introgression events. Moreover, population genetic processes unrelated to AI, such as background selection or heterosis, may create similar genomic signals to AI, compromising the reliability of methods that rely on neutral null distributions. In recent years, machine learning (ML) methods have been increasingly applied to population genetic questions. Here, we present a ML-based method called MaLAdapt for identifying AI loci from genome-wide sequencing data. Using an Extra-Trees Classifier algorithm, our method combines information from a large number of biologically meaningful summary statistics to capture a powerful composite signature of AI across the genome. In contrast to existing methods, MaLAdapt is especially well-powered to detect AI with mild beneficial effects, including selection on standing archaic variation, and is robust to non-AI selective sweeps, heterosis from deleterious mutations, and demographic misspecification. Further, MaLAdapt outperforms existing methods for detecting AI based on the analysis of simulated data and on a validation of empirical signals through visual inspection of haplotype patterns. We apply MaLAdapt to the 1000 Genomes Project human genomic data, and discover novel AI candidate regions in non-African populations, including genes that are enriched in functionally important biological pathways regulating metabolism and immune responses.

    View details for DOI 10.1093/molbev/msad001

    View details for PubMedID 36617238

  • Evolution and development of male-specific leg brushes in Drosophilidae. Development genes and evolution Tanaka, K., Barmina, O., Thompson, A., Massey, J. H., Kim, B. Y., Suvorov, A., Kopp, A. 2022

    Abstract

    The origin, diversification, and secondary loss of sexually dimorphic characters are common in animal evolution. In some cases, structurally and functionally similar traits have evolved independently in multiple lineages. Prominent examples of such traits include the male-specific grasping structures that develop on the front legs of many dipteran insects. In this report, we describe the evolution and development of one of these structures, the male-specific "sex brush." The sex brush is composed of densely packed, irregularly arranged modified bristles and is found in several distantly related lineages in the family Drosophilidae. Phylogenetic analysis using 250 genes from over 200 species provides modest support for a single origin of the sex brush followed by many secondary losses; however, independent origins of the sex brush cannot be ruled out completely. We show that sex brushes develop in very similar ways in all brush-bearing lineages. The dense packing of brush hairs is explained by the specification of bristle precursor cells at a near-maximum density permitted by the lateral inhibition mechanism, as well as by the reduced size of the surrounding epithelial cells. In contrast to the female and the ancestral male condition, where bristles are arranged in stereotypical, precisely spaced rows, cell migration does not contribute appreciably to the formation of the sex brush. The complex phylogenetic history of the sex brush can make it a valuable model for investigating coevolution of sex-specific morphology and mating behavior.

    View details for DOI 10.1007/s00427-022-00694-3

    View details for PubMedID 35939093

  • Secondary reversion to sexual monomorphism associated with tissue-specific loss of doublesex expression. Evolution; international journal of organic evolution Gao, J. J., Barmina, O., Thompson, A., Kim, B. Y., Suvorov, A., Tanaka, K., Watabe, H., Toda, M. J., Chen, J. M., Katoh, T. K., Kopp, A. 2022

    Abstract

    Animal evolution is characterized by frequent turnover of sexually dimorphic traits - new sex-specific characters are gained, and some ancestral sex-specific characters are lost, in many lineages. In insects, sexual differentiation is predominantly cell-autonomous and depends on the expression of the doublesex (dsx) transcription factor. In most cases, cells that transcribe dsx have the potential to undergo sex-specific differentiation, while those that lack dsx expression do not. Consistent with this mode of development, comparative research has shown that the origin of new sex-specific traits can be associated with the origin of new spatial domains of dsx expression. In this report, we examine the opposite situation - a secondary loss of the sex comb, a male-specific grasping structure that develops on the front legs of some drosophilid species. We show that, while the origin of the sex comb is linked to an evolutionary gain of dsx expression in the leg, sex comb loss in a newly identified species of Lordiphosa (Drosophilidae) is associated with a secondary loss of dsx expression. We discuss how the developmental control of sexual dimorphism affects the mechanisms by which sex-specific traits can evolve. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/evo.14564

    View details for PubMedID 35841603

  • MaLAdapt reveals novel targets of adaptive introgression in worldwide human populations Zhang, X., Singh, A., Durvasula, A., Kim, B., Lohmueller, K. WILEY. 2022: 204

    View details for Web of Science ID 000772245500766

  • Predictability and parallelism in the contemporary evolution of hybrid genomes. PLoS genetics Langdon, Q. K., Powell, D. L., Kim, B., Banerjee, S. M., Payne, C., Dodge, T. O., Moran, B., Fascinetto-Zago, P., Schumer, M. 1800; 18 (1): e1009914

    Abstract

    Hybridization between species is widespread across the tree of life. As a result, many species, including our own, harbor regions of their genome derived from hybridization. Despite the recognition that this process is widespread, we understand little about how the genome stabilizes following hybridization, and whether the mechanisms driving this stabilization tend to be shared across species. Here, we dissect the drivers of variation in local ancestry across the genome in replicated hybridization events between two species pairs of swordtail fish: Xiphophorus birchmanni * X. cortezi and X. birchmanni * X. malinche. We find unexpectedly high levels of repeatability in local ancestry across the two types of hybrid populations. This repeatability is attributable in part to the fact that the recombination landscape and locations of functionally important elements play a major role in driving variation in local ancestry in both types of hybrid populations. Beyond these broad scale patterns, we identify dozens of regions of the genome where minor parent ancestry is unusually low or high across species pairs. Analysis of these regions points to shared sites under selection across species pairs, and in some cases, shared mechanisms of selection. We show that one such region is a previously unknown hybrid incompatibility that is shared across X. birchmanni * X. cortezi and X. birchmanni * X. malinche hybrid populations.

    View details for DOI 10.1371/journal.pgen.1009914

    View details for PubMedID 35085234

  • Two new hybrid populations expand the swordtail hybridization model system. Evolution; international journal of organic evolution Powell, D. L., Moran, B., Kim, B., Banerjee, S. M., Aguillon, S. M., Fascinetto-Zago, P., Langdon, Q., Schumer, M. 2021

    Abstract

    Natural hybridization events provide unique windows into the barriers that keep species apart as well as the consequences of their breakdown. Here we characterize hybrid populations formed between the northern swordtail fish Xiphophorus cortezi and X. birchmanni from collection sites on two rivers. We use simulations and new genetic reference panels to develop sensitive and accurate local ancestry calling in this novel system. Strikingly, we find that hybrid populations on both rivers consist of two genetically distinct subpopulations: a cluster of pure X. birchmanni individuals and one of phenotypically intermediate hybrids that derive 85-90% of their genome from X. cortezi. Simulations suggest that initial hybridization occurred 150 generations ago at both sites, with little evidence for contemporary gene flow between subpopulations. This population structure is consistent with strong assortative mating between individuals of similar ancestry. The patterns of population structure uncovered here mirror those seen in hybridization between X. birchmanni and its sister species, X. malinche, indicating an important role for assortative mating in the evolution of hybrid populations. Future comparisons will provide a window into the shared mechanisms driving the outcomes of hybridization not only among independent hybridization events between the same species but also across distinct species pairs. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/evo.14337

    View details for PubMedID 34460102

  • Highly contiguous assemblies of 101 drosophilid genomes. eLife Kim, B. Y., Wang, J., Miller, D. E., Barmina, O., Delaney, E. K., Thompson, A., Comeault, A. A., Peede, D., D'Agostino, E. R., Pelaez, J., Aguilar, J. M., Haji, D., Matsunaga, T., Armstrong, E., Zych, M., Ogawa, Y., Stamenkovic-Radak, M., Jelic, M., Veselinovic, M. S., Tanaskovic, M., Eric, P., Gao, J., Katoh, T. K., Toda, M. J., Watabe, H., Watada, M., Davis, J. S., Moyle, L., Manoli, G., Bertolini, E., Kostal, V., Hawley, R. S., Takahashi, A., Jones, C. D., Price, D. K., Whiteman, N. K., Kopp, A., Matute, D. R., Petrov, D. A. 2021; 10

    Abstract

    Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. We show that Nanopore-based assemblies are highly accurate in coding regions, particularly with respect to coding insertions and deletions. These assemblies, along with a detailed laboratory protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution at the scale of hundreds of species.

    View details for DOI 10.7554/eLife.66405

    View details for PubMedID 34279216

  • Broad geographic sampling reveals the shared basis and environmental correlates of seasonal adaptation in Drosophila. eLife Machado, H. E., Bergland, A., Taylor, R. W., Tilk, S., Behrman, E., Dyer, K., Fabian, D. K., Flatt, T., Gonzalez, J., Karasov, T. L., Kim, B. Y., Kozeretska, I., Lazzaro, B. P., Merritt, T., Pool, J. E., O'Brien, K., Rajpurohit, S., Roy, P. R., Schaeffer, S. W., Serga, S., Schmidt, P., Petrov, D. A. 2021; 10

    Abstract

    To advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel among Drosophila melanogaster populations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched in large chromosomal inversions and we find a broad concordance between seasonal and spatial allele frequency change. The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling, linking the environment and the genomic response to selection. Our results suggest that fluctuating selection is an important evolutionary force affecting patterns of genetic variation in Drosophila.

    View details for DOI 10.7554/eLife.67577

    View details for PubMedID 34155971

  • Widespread introgression across a phylogeny of 155 Drosophila genomes. Current biology : CB Suvorov, A., Kim, B. Y., Wang, J., Armstrong, E. E., Peede, D., D'Agostino, E. R., Price, D. K., Waddell, P., Lang, M., Courtier-Orgogozo, V., David, J. R., Petrov, D., Matute, D. R., Schrider, D. R., Comeault, A. A. 2021

    Abstract

    Genome-scale sequence data have invigorated the study of hybridization and introgression, particularly in animals. However, outside of a few notable cases, we lack systematic tests for introgression at a larger phylogenetic scale across entire clades. Here, we leverage 155 genome assemblies from 149 species to generate a fossil-calibrated phylogeny and conduct multilocus tests for introgression across 9 monophyletic radiations within the genus Drosophila. Using complementary phylogenomic approaches, we identify widespread introgression across the evolutionary history of Drosophila. Mapping gene-tree discordance onto the phylogeny revealed that both ancient and recent introgression has occurred across most of the 9 clades that we examined. Our results provide the first evidence of introgression occurring across the evolutionary history of Drosophila and highlight the need to continue to study the evolutionary consequences of hybridization and introgression in this genus and across the tree of life.

    View details for DOI 10.1016/j.cub.2021.10.052

    View details for PubMedID 34788634

  • A community-maintained standard library of population genetic models. eLife Adrion, J. R., Cole, C. B., Dukler, N., Galloway, J. G., Gladstein, A. L., Gower, G., Kyriazis, C. C., Ragsdale, A. P., Tsambos, G., Baumdicker, F., Carlson, J., Cartwright, R. A., Durvasula, A., Gronau, I., Kim, B. Y., McKenzie, P., Messer, P. W., Noskova, E., Ortega Del Vecchyo, D., Racimo, F., Struck, T. J., Gravel, S., Gutenkunst, R. N., Lohmueller, K. E., Ralph, P. L., Schrider, D. R., Siepel, A., Kelleher, J., Kern, A. D. 2020; 9

    Abstract

    The explosion in population genomic data demands ever more complex modes of analysis, and increasingly these analyses depend on sophisticated simulations. Re-cent advances in population genetic simulation have made it possible to simulate large and complex models, but specifying such models for a particular simulation engine remains a difficult and error-prone task. Computational genetics researchers currently re-implement simulation models independently, leading to inconsistency and duplication of effort. This situation presents a major barrier to empirical researchers seeking to use simulations for power analyses of upcoming studies or sanity checks on existing genomic data. Population genetics, as a field, also lacks standard benchmarks by which new tools for inference might be measured. Here we describe a new resource, stdpopsim, that attempts to rectify this situation. Stdpopsim is a community-driven open source project, which provides easy access to a growing catalog of published simulation models from a range of organisms and supports multiple simulation engine backends. This resource is available as a well-documented python library with a simple command-line interface. We share some examples demonstrating how stdpopsim can be used to systematically compare demographic inference methods, and we encourage a broader community of developers to contribute to this growing resource.

    View details for DOI 10.7554/eLife.54967

    View details for PubMedID 32573438

  • The Impact of Recessive Deleterious Variation on Signals of Adaptive Introgression in Human Populations. Genetics Zhang, X., Kim, B., Lohmueller, K. E., Huerta-Sanchez, E. 2020

    Abstract

    Admixture with archaic hominins has altered the landscape of genomic variation in modern human populations. Several gene regions have been previously identified as candidates of adaptive introgression (AI) that facilitated human adaptation to specific environments. However, simulation-based studies have suggested that population genetic processes other than adaptive mutations, such as heterosis from recessive deleterious variants private to populations before admixture, can also lead to patterns in genomic data that resemble adaptive introgression. The extent to which the presence of deleterious variants affect the false-positive rate and the power of current methods to detect AI has not been fully assessed. Here, we used extensive simulations under parameters relevant for human evolution to show that recessive deleterious mutations can increase the false positive rates of tests for AI compared to models without deleterious variants, especially when the recombination rates are low. We next examined candidates of AI in modern humans identified from previous studies and show that 24 out of 26 candidate regions remain significant even when deleterious variants are included in the null model. However, two AI candidate genes, HYAL2 and HLA, are particularly susceptible to high false positive signals of AI due to recessive deleterious mutations. These genes are located in regions of the human genome with high exon density together with low recombination rate, factors that we show increase the rate of false-positives due to recessive deleterious mutations. Although the combination of such parameters is rare in the human genome, caution is warranted in such regions as well as in other species with more compact genomes and/or lower recombination rates. In sum, our results suggest that recessive deleterious mutations cannot account for the signals of AI in most, but not all, of the top candidates for AI in humans, suggesting they may be genuine signals of adaptation.

    View details for DOI 10.1534/genetics.120.303081

    View details for PubMedID 32487519

  • Population genetic models of GERP scores suggest pervasive turnover of constrained sites across mammalian evolution PLOS GENETICS Huber, C. D., Kim, B. Y., Lohmueller, K. E. 2020; 16 (5)

    View details for DOI 10.1371/journal.pgen.1008827.r004

    View details for Web of Science ID 000538052400038

  • Population genetic models of GERP scores suggest pervasive turnover of constrained sites across mammalian evolution. PLoS genetics Huber, C. D., Kim, B. Y., Lohmueller, K. E. 2020; 16 (5): e1008827

    Abstract

    Comparative genomic approaches have been used to identify sites where mutations are under purifying selection and of functional consequence by searching for sequences that are conserved across distantly related species. However, the performance of these approaches has not been rigorously evaluated under population genetic models. Further, short-lived functional elements may not leave a footprint of sequence conservation across many species. We use simulations to study how one measure of conservation, the Genomic Evolutionary Rate Profiling (GERP) score, relates to the strength of selection (Nes). We show that the GERP score is related to the strength of purifying selection. However, changes in selection coefficients or functional elements over time (i.e. functional turnover) can strongly affect the GERP distribution, leading to unexpected relationships between GERP and Nes. Further, we show that for functional elements that have a high turnover rate, adding more species to the analysis does not necessarily increase statistical power. Finally, we use the distribution of GERP scores across the human genome to compare models with and without turnover of sites where mutations under purifying selection. We show that mutations in 4.51% of the noncoding human genome are under purifying selection and that most of this sequence has likely experienced changes in selection coefficients throughout mammalian evolution. Our work reveals limitations to using comparative genomic approaches to identify deleterious mutations. Commonly used GERP score thresholds miss over half of the noncoding sites in the human genome where mutations are under purifying selection.

    View details for DOI 10.1371/journal.pgen.1008827

    View details for PubMedID 32469868

  • Identification and Characterization of Breakpoints and Mutations on Drosophila melanogaster Balancer Chromosomes. G3 (Bethesda, Md.) Miller, D. E., Kahsai, L. n., Buddika, K. n., Dixon, M. J., Kim, B. Y., Calvi, B. R., Sokol, N. S., Hawley, R. S., Cook, K. R. 2020

    Abstract

    Balancers are rearranged chromosomes used in Drosophila melanogaster to maintain deleterious mutations in stable populations, preserve sets of linked genetic elements and construct complex experimental stocks. Here, we assess the phenotypes associated with breakpoint-induced mutations on commonly used third chromosome balancers and show remarkably few deleterious effects. We demonstrate that a breakpoint in p53 causes loss of radiation-induced apoptosis and a breakpoint in Fucosyltransferase A causes loss of fucosylation in nervous and intestinal tissue-the latter study providing new markers for intestinal cell identity and challenging previous conclusions about the regulation of fucosylation. We also describe thousands of potentially harmful mutations shared among X or third chromosome balancers, or unique to specific balancers, including an Ankyrin 2 mutation present on most TM3 balancers, and reiterate the risks of using balancers as experimental controls. We used long-read sequencing to confirm or refine the positions of two inversions with breakpoints lying in repetitive sequences and provide evidence that one of the inversions, In(2L)Cy, arose by ectopic recombination between foldback transposon insertions and the other, In(3R)C, cleanly separates subtelomeric and telomeric sequences and moves the subtelomeric sequences to an internal chromosome position. In addition, our characterization of In(3R)C shows that balancers may be polymorphic for terminal deletions. Finally, we present evidence that extremely distal mutations on balancers can add to the stability of stocks whose purpose is to maintain homologous chromosomes carrying mutations in distal genes. Overall, these studies add to our understanding of the structure, diversity and effectiveness of balancer chromosomes.

    View details for DOI 10.1534/g3.120.401559

    View details for PubMedID 32972999