Bernard Youngsoo Kim

All Publications

• 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