@article{schwarzkopf_brandt_heil_2024, title={The recombination landscape of introgression in yeast}, url={https://doi.org/10.1101/2024.01.04.574263}, DOI={10.1101/2024.01.04.574263}, abstractNote={Abstract}, author={Schwarzkopf, Enrique J. and Brandt, Nathan and Heil, Caiti Smukowski}, year={2024}, month={Jan} } @article{schwarzkopf_brandt_heil_2024, title={The recombination landscape of introgression in yeast}, url={https://doi.org/10.7554/eLife.96184.1}, DOI={10.7554/eLife.96184.1}, abstractNote={Meiotic recombination is an important evolutionary force that acts by breaking up genomic linkage, thereby increasing the efficacy of selection. Meiotic recombination is initiated with a double-strand break which is resolved via a crossover, which involves the reciprocal exchange of genetic material between homologous chromosomes, or a non-crossover, which results in small tracts of non-reciprocal exchange of genetic material. While the meiotic process is largely conserved, crossover and non-crossover rates vary between species, populations, individuals, and across the genome. In recent years, recombination is observed to be positively associated with the distribution of ancestry derived from past interspecific hybridization (introgression) in a variety of species. This trend has been interpreted to signify that introgression carries genetic incompatibilities that are selected against, such that introgression is enriched in regions of high recombination. However, recombination is well known to be suppressed in divergent sequence to prevent non-homologous recombination. Since introgressed DNA is often divergent, we sought to explore this interaction of recombination and introgression by sequencing spores and detecting crossover and non-crossover events from two crosses of the budding yeast Saccharomyces uvarum . One cross is between strains isolated from natural environments, and the other cross is between strains from fermentation environments, in which each strain contains introgression from their sister species, S. eubayanus . We find that the recombination landscape is significantly different between S. uvarum crosses, and that most of these differences can be explained by the presence of heterozygous introgression in the fermentation cross. Crossovers are significantly reduced and non-crossovers are increased in heterozygous introgression compared to syntenic regions in the natural cross without introgression. This translates to reduced allele shuffling within introgressed regions, and an overall reduction of shuffling on most chromosomes with introgression compared to the syntenic regions and chromosomes without introgression. Our results indicate that recent hybridization can significantly influence the recombination landscape, and suggest that the reduction in allele shuffling contributes to the initial purging of introgressed ancestry in the generations following a hybridization event. }, author={Schwarzkopf, Enrique J. and Brandt, Nathan and Heil, Caiti Smukowski}, year={2024}, month={Mar} } @article{schwarzkopf_brandt_heil_2024, title={The recombination landscape of introgression in yeast}, url={https://doi.org/10.7554/eLife.96184}, DOI={10.7554/eLife.96184}, abstractNote={Meiotic recombination is an important evolutionary force that acts by breaking up genomic linkage, thereby increasing the efficacy of selection. Meiotic recombination is initiated with a double-strand break which is resolved via a crossover, which involves the reciprocal exchange of genetic material between homologous chromosomes, or a non-crossover, which results in small tracts of non-reciprocal exchange of genetic material. While the meiotic process is largely conserved, crossover and non-crossover rates vary between species, populations, individuals, and across the genome. In recent years, recombination is observed to be positively associated with the distribution of ancestry derived from past interspecific hybridization (introgression) in a variety of species. This trend has been interpreted to signify that introgression carries genetic incompatibilities that are selected against, such that introgression is enriched in regions of high recombination. However, recombination is well known to be suppressed in divergent sequence to prevent non-homologous recombination. Since introgressed DNA is often divergent, we sought to explore this interaction of recombination and introgression by sequencing spores and detecting crossover and non-crossover events from two crosses of the budding yeast Saccharomyces uvarum . One cross is between strains isolated from natural environments, and the other cross is between strains from fermentation environments, in which each strain contains introgression from their sister species, S. eubayanus . We find that the recombination landscape is significantly different between S. uvarum crosses, and that most of these differences can be explained by the presence of heterozygous introgression in the fermentation cross. Crossovers are significantly reduced and non-crossovers are increased in heterozygous introgression compared to syntenic regions in the natural cross without introgression. This translates to reduced allele shuffling within introgressed regions, and an overall reduction of shuffling on most chromosomes with introgression compared to the syntenic regions and chromosomes without introgression. Our results indicate that recent hybridization can significantly influence the recombination landscape, and suggest that the reduction in allele shuffling contributes to the initial purging of introgressed ancestry in the generations following a hybridization event. }, author={Schwarzkopf, Enrique J. and Brandt, Nathan and Heil, Caiti Smukowski}, year={2024}, month={Mar} } @article{heil_2023, title={Loss of Heterozygosity and Its Importance in Evolution}, volume={2}, ISSN={["1432-1432"]}, url={https://doi.org/10.1007/s00239-022-10088-8}, DOI={10.1007/s00239-022-10088-8}, abstractNote={Abstract}, journal={JOURNAL OF MOLECULAR EVOLUTION}, author={Heil, Caiti Smukowski}, year={2023}, month={Feb} } @article{madden_lahue_gordy_little_nichols_calvert_dunn_smukowski heil_2021, title={Sugar‐seeking insects as a source of diverse bread‐making yeasts with enhanced attributes}, volume={39}, ISSN={0749-503X 1097-0061}, url={http://dx.doi.org/10.1002/yea.3676}, DOI={10.1002/yea.3676}, abstractNote={Abstract}, number={1-2}, journal={Yeast}, publisher={Wiley}, author={Madden, Anne A. and Lahue, Caitlin and Gordy, Claire L. and Little, Joy L. and Nichols, Lauren M. and Calvert, Martha D. and Dunn, Robert R. and Smukowski Heil, Caiti}, year={2021}, month={Nov}, pages={108–127} } @inbook{heil_lahue_2021, title={The Evolutionary History of Bread and Beer Yeast}, url={http://dx.doi.org/10.52750/526619}, DOI={10.52750/526619}, abstractNote={She studies the evolution of yeasts (including their hybridization).Here she will tell the story of the evolution of the yeasts used in bread and wine and how those yeasts have changed as they've been domesticated.She'll also mention the ways in which the wild yeasts that colonize sourdough starters are likely to differ from commercial yeasts (and why).Caiti Heil will team up with her colleague Caiti LaHue for this talk.The Caitis will also consider the ways in which the evolution of yeast reminds us about and elucidates the workings of evolution and natural selection more generally.}, booktitle={Fermentology}, publisher={North Carolina State University Libraries}, author={Heil, Caiti and Lahue, Caiti}, editor={Dufresne, KelseyEditor}, year={2021}, month={May} } @article{heil_patterson_hickey_alcantara_dunham_2020, title={Transposable element mobilization in interspecific yeast hybrids}, volume={6}, url={https://doi.org/10.1101/2020.06.16.155218}, DOI={10.1101/2020.06.16.155218}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Heil, Caiti Smukowski and Patterson, Kira and Hickey, Angela Shang-Mei and Alcantara, Erica and Dunham, Maitreya J.}, year={2020}, month={Jun} } @article{lancaster_payen_heil_dunham_2019, title={Fitness benefits of loss of heterozygosity in Saccharomyces hybrids}, volume={29}, url={https://doi.org/10.1101/gr.245605.118}, DOI={10.1101/gr.245605.118}, abstractNote={With two genomes in the same organism, interspecific hybrids have unique fitness opportunities and costs. In both plants and yeasts, wild, pathogenic, and domesticated hybrids may eliminate portions of one parental genome, a phenomenon known as loss of heterozygosity (LOH). Laboratory evolution of hybrid yeast recapitulates these results, with LOH occurring in just a few hundred generations of propagation. In this study, we systematically looked for alleles that are beneficial when lost in order to determine how prevalent this mode of adaptation may be and to determine candidate loci that might underlie the benefits of larger-scale chromosome rearrangements. These aims were accomplished by mating Saccharomyces uvarum with the S. cerevisiae deletion collection to create hybrids such that each nonessential S. cerevisiae allele is deleted. Competitive fitness assays of these pooled, barcoded, hemizygous strains, and accompanying controls, revealed a large number of loci for which LOH is beneficial. We found that the fitness effects of hemizygosity are dependent on the species context, the selective environment, and the species origin of the deleted allele. Further, we found that hybrids have a wider distribution of fitness consequences versus matched S. cerevisiae hemizygous diploids. Our results suggest that LOH can be a successful strategy for adaptation of hybrids to new environments, and we identify candidate loci that drive the chromosomal rearrangements observed in evolution of yeast hybrids.}, number={10}, journal={Genome Research}, publisher={Cold Spring Harbor Laboratory}, author={Lancaster, Samuel M. and Payen, Celia and Heil, Caiti Smukowski and Dunham, Maitreya J.}, year={2019}, month={Oct}, pages={1685–1692} } @article{heil_large_patterson_hickey_yeh_dunham_2019, title={Temperature preference can bias parental genome retention during hybrid evolution}, volume={15}, url={https://doi.org/10.1371/journal.pgen.1008383}, DOI={10.1371/journal.pgen.1008383}, abstractNote={Interspecific hybridization can introduce genetic variation that aids in adaptation to new or changing environments. Here, we investigate how hybrid adaptation to temperature and nutrient limitation may alter parental genome representation over time. We evolved Saccharomyces cerevisiae x Saccharomyces uvarum hybrids in nutrient-limited continuous culture at 15°C for 200 generations. In comparison to previous evolution experiments at 30°C, we identified a number of responses only observed in the colder temperature regime, including the loss of the S. cerevisiae allele in favor of the cryotolerant S. uvarum allele for several portions of the hybrid genome. In particular, we discovered a genotype by environment interaction in the form of a loss of heterozygosity event on chromosome XIII; which species’ haplotype is lost or maintained is dependent on the parental species’ temperature preference and the temperature at which the hybrid was evolved. We show that a large contribution to this directionality is due to a temperature dependent fitness benefit at a single locus, the high affinity phosphate transporter gene PHO84. This work helps shape our understanding of what forces impact genome evolution after hybridization, and how environmental conditions may promote or disfavor the persistence of hybrids over time.}, number={9}, journal={PLOS Genetics}, publisher={Public Library of Science (PLoS)}, author={Heil, Caiti S. Smukowski and Large, Christopher R. L. and Patterson, Kira and Hickey, Angela Shang-Mei and Yeh, Chiann-Ling C. and Dunham, Maitreya J.}, editor={HITTINGER, CHRIS TODDEditor}, year={2019}, month={Sep}, pages={e1008383} } @article{lancaster_payen_heil_dunham_2018, title={Fitness Benefits of Loss of Heterozygosity in Saccharomyces Hybrids}, volume={10}, url={https://doi.org/10.1101/452748}, DOI={10.1101/452748}, abstractNote={ABSTRACT}, publisher={Cold Spring Harbor Laboratory}, author={Lancaster, Samuel M. and Payen, Celia and Heil, Caiti Smukowski and Dunham, Maitreya J.}, year={2018}, month={Oct} } @article{heil_large_patterson_dunham_2018, title={Temperature preference biases parental genome retention during hybrid evolution}, volume={9}, url={https://doi.org/10.1101/429803}, DOI={10.1101/429803}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Heil, Caiti Smukowski and Large, Christopher R. L. and Patterson, Kira and Dunham, Maitreya J.}, year={2018}, month={Sep} } @article{hope_amorosi_miller_dang_heil_dunham_2017, title={Experimental Evolution Reveals Favored Adaptive Routes to Cell Aggregation in Yeast}, volume={206}, DOI={10.1534/genetics.116.198895}, abstractNote={Abstract}, number={2}, journal={Genetics}, publisher={Genetics Society of America}, author={Hope, Elyse A. and Amorosi, Clara J. and Miller, Aaron W. and Dang, Kolena and Heil, Caiti Smukowski and Dunham, Maitreya J.}, year={2017}, month={Apr}, pages={1153–1167} } @article{heil_burton_liachko_friedrich_hanson_morris_schacherer_shendure_thomas_dunham_2017, title={Identification of a novel interspecific hybrid yeast from a metagenomic spontaneously inoculated beer sample using Hi-C}, volume={6}, DOI={10.1101/150722}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Heil, Caiti Smukowski and Burton, Joshua N. and Liachko, Ivan and Friedrich, Anne and Hanson, Noah A. and Morris, Cody L. and Schacherer, Joseph and Shendure, Jay and Thomas, James H. and Dunham, Maitreya J.}, year={2017}, month={Jun} } @article{heil_desevo_pai_tucker_hoang_dunham_2017, title={Loss of Heterozygosity Drives Adaptation in Hybrid Yeast}, volume={34}, DOI={10.1093/molbev/msx098}, abstractNote={Abstract Hybridization is often considered maladaptive, but sometimes hybrids can invade new ecological niches and adapt to novel or stressful environments better than their parents. The genomic changes that occur following hybridization that facilitate genome resolution and/or adaptation are not well understood. Here, we examine hybrid genome evolution using experimental evolution of de novo interspecific hybrid yeast Saccharomyces cerevisiae × Saccharomyces uvarum and their parentals. We evolved these strains in nutrient-limited conditions for hundreds of generations and sequenced the resulting cultures identifying numerous point mutations, copy number changes, and loss of heterozygosity (LOH) events, including species-biased amplification of nutrient transporters. We focused on a particularly interesting example, in which we saw repeated LOH at the high-affinity phosphate transporter gene PHO84 in both intra- and interspecific hybrids. Using allele replacement methods, we tested the fitness of different alleles in hybrid and S. cerevisiae strain backgrounds and found that the LOH is indeed the result of selection on one allele over the other in both S. cerevisiae and the hybrids. This is an example where hybrid genome resolution is driven by positive selection on existing heterozygosity and demonstrates that even infrequent outcrossing may have lasting impacts on adaptation.}, number={7}, journal={Molecular Biology and Evolution}, publisher={Oxford University Press (OUP)}, author={Heil, Caiti S. Smukowski and DeSevo, Christopher G. and Pai, Dave A. and Tucker, Cheryl M. and Hoang, Margaret L. and Dunham, Maitreya J.}, year={2017}, month={Mar}, pages={1596–1612} } @article{hope_amorosi_miller_dang_heil_dunham_2016, title={Experimental evolution reveals favored adaptive routes to cell aggregation in yeast}, volume={12}, DOI={10.1101/091876}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Hope, Elyse A. and Amorosi, Clara J. and Miller, Aaron W. and Dang, Kolena and Heil, Caiti Smukowski and Dunham, Maitreya J.}, year={2016} } @article{heil_ellison_dubin_noor_2015, title={Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species ofDrosophila}, volume={7}, DOI={10.1093/gbe/evv182}, abstractNote={Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in Metazoans by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present what may be the most comprehensive portrait of recombination to date, combining contemporary recombination estimates from each of two sister species along with historic estimates of recombination using linkage-disequilibrium-based approaches derived from sequence data from both species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we replicate the pattern seen in human-chimpanzee that recombination rate is conserved at broad scales and more divergent at finer scales. We also find evidence of a species-wide recombination modifier, resulting in both a present and historic genome wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inter-species inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. Author Summary Recombination, or crossing over, describes an essential exchange of genetic material that occurs during egg and sperm development and has consequences for the proper segregation of chromosomes, and for the evolution of genomes and genomic features. In our study, we compare genome wide recombination rate in two closely related species of the fruit fly Drosophila to understand if and how recombination changes over time. We find that recombination does indeed change, we observe globally increased recombination in one species, and differences in regional recombination likely reflecting the result of a chromosomal rearrangement in both species. Moreover, we show that the extent that recombination changes is dependent on the physical scale at which recombination is measured, likely reflecting selection pressures on recombination distribution and replicating a pattern seen in human-chimpanzee recombination. Apart from between-species differences, we note several ways in which the Drosophila recombination landscape has changed since Drosophila diverged from other organisms. In contrast to species of fungi, plants, and animals, Drosophila recombination is not concentrated in discrete regions known as hotspots, nor is it increased near the start of genes, suggesting that despite the importance of the recombination process, the determinants of recombination have been shifting over evolutionary time.}, number={10}, journal={Genome Biology and Evolution}, publisher={Oxford University Press (OUP)}, author={Heil, Caiti S. Smukowski and Ellison, Chris and Dubin, Matthew and Noor, Mohamed A.F.}, year={2015}, month={Oct}, pages={2829–2842} } @article{heil_ellison_dubin_noor_2015, title={Recombining without hotspots: A comprehensive evolutionary portrait of recombination in two closely related species of Drosophila}, volume={3}, DOI={10.1101/016972}, abstractNote={Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in Metazoans by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present what may be the most comprehensive portrait of recombination to date, combining contemporary recombination estimates from each of two sister species along with historic estimates of recombination using linkage-disequilibrium-based approaches derived from sequence data from both species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we replicate the pattern seen in human-chimpanzee that recombination rate is conserved at broad scales and more divergent at finer scales. We also find evidence of a species-wide recombination modifier, resulting in both a present and historic genome wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inter-species inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms.}, publisher={Cold Spring Harbor Laboratory}, author={Heil, Caiti Smukowski and Ellison, Chris and Dubin, Matthew and Noor, Mohamed}, year={2015}, month={Mar} } @article{heil_2014, title={ No Detectable Effect of the DNA Methyltransferase DNMT2 on Drosophila Meiotic Recombination }, volume={4}, DOI={10.1534/g3.114.012393}, abstractNote={Abstract}, number={11}, journal={G3: Genes|Genomes|Genetics}, publisher={Genetics Society of America}, author={Heil, Caiti S. Smukowski}, year={2014}, month={Aug}, pages={2095–2100} } @article{heil_noor_2012, title={Mentor vs. Monolith}, volume={100}, DOI={10.1511/2012.99.450}, number={6}, journal={American Scientist}, publisher={Sigma Xi}, author={Heil, Caiti and Noor, Mohamed}, year={2012}, pages={450} } @article{mcgaugh_heil_manzano-winkler_loewe_goldstein_himmel_noor_2012, title={Recombination Modulates How Selection Affects Linked Sites in Drosophila}, volume={10}, DOI={10.1371/journal.pbio.1001422}, abstractNote={Recombination rate in Drosophila species shapes the impact of selection in the genome and is positively correlated with nucleotide diversity.}, number={11}, journal={PLoS Biology}, publisher={Public Library of Science (PLoS)}, author={McGaugh, Suzanne E. and Heil, Caiti S. S. and Manzano-Winkler, Brenda and Loewe, Laurence and Goldstein, Steve and Himmel, Tiffany L. and Noor, Mohamed A. F.}, editor={Barton, Nick H.Editor}, year={2012}, month={Nov}, pages={e1001422} } @article{heil_hunter_noor_miglia_manzano-winkler_mcdermott_noor_2012, title={Witnessing Phenotypic and Molecular Evolution in the Fruit Fly}, volume={5}, DOI={10.1007/s12052-012-0447-5}, abstractNote={Abstract}, number={4}, journal={Evolution: Education and Outreach}, publisher={Springer Nature}, author={Heil, Caiti S. S. and Hunter, Mika J. and Noor, Juliet K. F. and Miglia, Kathleen and Manzano-Winkler, Brenda and McDermott, Shannon R. and Noor, Mohamed A. F.}, year={2012}, month={Sep}, pages={629–634} } @article{heil_noor_2012, title={Zinc Finger Binding Motifs Do Not Explain Recombination Rate Variation within or between Species of Drosophila}, volume={7}, DOI={10.1371/journal.pone.0045055}, abstractNote={In humans and mice, the Cys2His2 zinc finger protein PRDM9 binds to a DNA sequence motif enriched in hotspots of recombination, possibly modifying nucleosomes, and recruiting recombination machinery to initiate Double Strand Breaks (DSBs). However, since its discovery, some researchers have suggested that the recombinational effect of PRDM9 is lineage or species specific. To test for a conserved role of PRDM9-like proteins across taxa, we use the Drosophila pseudoobscura species group in an attempt to identify recombination associated zinc finger proteins and motifs. We leveraged the conserved amino acid motifs in Cys2His2 zinc fingers to predict nucleotide binding motifs for all Cys2His2 zinc finger proteins in Drosophila pseudoobscura and identified associations with empirical measures of recombination rate. Additionally, we utilized recombination maps from D. pseudoobscura and D. miranda to explore whether changes in the binding motifs between species can account for changes in the recombination landscape, analogous to the effect observed in PRDM9 among human populations. We identified a handful of potential recombination-associated sequence motifs, but the associations are generally tenuous and their biological relevance remains uncertain. Furthermore, we found no evidence that changes in zinc finger DNA binding explains variation in recombination rate between species. We therefore conclude that there is no protein with a DNA sequence specific human-PRDM9-like function in Drosophila. We suggest these findings could be explained by the existence of a different recombination initiation system in Drosophila.}, number={9}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Heil, Caiti S. S. and Noor, Mohamed A. F.}, editor={Singh, NadiaEditor}, year={2012}, month={Sep}, pages={e45055} } @article{smukowski_noor_2011, title={Recombination rate variation in closely related species}, volume={107}, DOI={10.1038/hdy.2011.44}, abstractNote={Despite their importance to successful meiosis and various evolutionary processes, meiotic recombination rates sometimes vary within species or between closely related species. For example, humans and chimpanzees share virtually no recombination hotspot locations in the surveyed portion of the genomes. However, conservation of recombination rates between closely related species has also been documented, raising an apparent contradiction. Here, we evaluate how and why conflicting patterns of recombination rate conservation and divergence may be observed, with particular emphasis on features that affect recombination, and the scale and method with which recombination is surveyed. Additionally, we review recent studies identifying features influencing fine-scale and broad-scale recombination patterns and informing how quickly recombination rates evolve, how changes in recombination impact selection and evolution in natural populations, and more broadly, which forces influence genome evolution.}, number={6}, journal={Heredity}, publisher={Springer Nature}, author={Smukowski, C S and Noor, M A F}, year={2011}, month={Jun}, pages={496–508} }