@article{jain_bakolitsa_brenner_radivojac_moult_repo_hoskins_andreoletti_barsky_chellapan_et al._2024, title={CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods}, volume={25}, ISSN={["1474-760X"]}, DOI={10.1186/s13059-023-03113-6}, abstractNote={Abstract}, number={1}, journal={GENOME BIOLOGY}, author={Jain, Shantanu and Bakolitsa, Constantina and Brenner, Steven E. and Radivojac, Predrag and Moult, John and Repo, Susanna and Hoskins, Roger A. and Andreoletti, Gaia and Barsky, Daniel and Chellapan, Ajithavalli and et al.}, year={2024}, month={Feb} }
 @article{ogbunugafor_guerrero_miller-dickson_shakhnovich_shoulders_2023, title={Epistasis and pleiotropy shape biophysical protein subspaces associated with drug resistance}, volume={108}, ISSN={["2470-0053"]}, url={https://doi.org/10.1103/PhysRevE.108.054408}, DOI={10.1103/PhysRevE.108.054408}, abstractNote={Protein space is a rich analogy for genotype-phenotype maps, where amino acid sequence is organized into a high-dimensional space that highlights the connectivity between protein variants. It is a useful abstraction for understanding the process of evolution, and for efforts to engineer proteins towards desirable phenotypes. Few mentions of protein space consider how protein phenotypes can be described in terms of their biophysical components, nor do they rigorously interrogate how forces like epistasis-describing the nonlinear interaction between mutations and their phenotypic consequences-manifest across these components. In this study, we deconstruct a low-dimensional protein space of a bacterial enzyme (dihydrofolate reductase; DHFR) into "subspaces" corresponding to a set of kinetic and thermodynamic traits [k_{cat}, K_{M}, K_{i}, and T_{m} (melting temperature)]. We then examine how combinations of three mutations (eight alleles in total) display pleiotropy, or unique effects on individual subspace traits. We examine protein spaces across three orthologous DHFR enzymes (Escherichia coli, Listeria grayi, and Chlamydia muridarum), adding a genotypic context dimension through which epistasis occurs across subspaces. In doing so, we reveal that protein space is a deceptively complex notion, and that future applications to bioengineering should consider how interactions between amino acid substitutions manifest across different phenotypic subspaces.}, number={5}, journal={PHYSICAL REVIEW E}, author={Ogbunugafor, C. Brandon and Guerrero, Rafael F. and Miller-Dickson, Miles D. and Shakhnovich, Eugene I. and Shoulders, Matthew D.}, year={2023}, month={Nov} }
 @article{ogbunugafor_guerrero_shakhnovich_shoulders_2023, title={Epistasis meets pleiotropy in shaping biophysical protein subspaces associated with antimicrobial resistance}, url={https://doi.org/10.1101/2023.04.09.535490}, DOI={10.1101/2023.04.09.535490}, abstractNote={Abstract}, author={Ogbunugafor, C. Brandon and Guerrero, Rafael F. and Shakhnovich, Eugene I. and Shoulders, Matthew D.}, year={2023}, month={Apr} }
 @article{guerrero_dorji_harris_shoulders_ogbunugafor_2023, title={Evolutionary druggability: leveraging low-dimensional fitness landscapes towards new metrics for antimicrobial applications}, url={https://doi.org/10.1101/2023.04.08.536116}, DOI={10.1101/2023.04.08.536116}, abstractNote={Abstract}, author={Guerrero, Rafael F. and Dorji, Tandin and Harris, Ra’Mal M. and Shoulders, Matthew D. and Ogbunugafor, C. Brandon}, year={2023}, month={Apr} }
 @article{guerrero_dorji_harris_shoulders_ogbunugafor_2023, title={Evolutionary druggability: leveraging low-dimensional fitness landscapes towards new metrics for antimicrobial applications}, url={https://doi.org/10.7554/eLife.88480.1}, DOI={10.7554/eLife.88480.1}, abstractNote={The term “druggability” describes the molecular properties of drugs or targets in pharmacological interventions and is commonly used in work involving drug development for clinical applications. There are no current analogues for this notion that quantify the drug-target interaction with respect to a given target variant’s sensitivity across a breadth of drugs in a panel, or a given drug’s range of effectiveness across alleles of a target protein. Using data from low-dimensional empirical fitness landscapes composed of 16 β-lactamase alleles and seven β-lactam drugs, we introduce two metrics that capture (i) the average susceptibility of an allelic variant of a drug target to any available drug in a given panel (“variant vulnerability”), and (ii) the average applicability of a drug (or mixture) across allelic variants of a drug target (“drug applicability”). Finally, we (iii) disentangle the quality and magnitude of interactions between loci in the drug target and the seven drug environments in terms of their mutation by mutation by environment (G x G x E) interactions, offering mechanistic insight into the variant variability and drug applicability metrics. Summarizing, we propose that our framework can be applied to other datasets and pathogen-drug systems to understand which pathogen variants in a clinical setting are the most concerning (low variant vulnerability), and which drugs in a panel are most likely to be effective in an infection defined by standing genetic variation in the pathogen drug target (high drug applicability).}, author={Guerrero, Rafael F. and Dorji, Tandin and Harris, Ra’Mal M. and Shoulders, Matthew D. and Ogbunugafor, C. Brandon}, year={2023}, month={Aug} }
 @article{guerrero_dorji_harris_shoulders_ogbunugafor_2023, title={Evolutionary druggability: leveraging low-dimensional fitness landscapes towards new metrics for antimicrobial applications}, url={https://doi.org/10.7554/eLife.88480.2}, DOI={10.7554/eLife.88480.2}, abstractNote={The term “druggability” describes the molecular properties of drugs or targets in pharmacological interventions and is commonly used in work involving drug development for clinical applications. There are no current analogues for this notion that quantify the drug-target interaction with respect to a given target variant’s sensitivity across a breadth of drugs in a panel, or a given drug’s range of effectiveness across alleles of a target protein. Using data from low-dimensional empirical fitness landscapes composed of 16 β-lactamase alleles and seven β-lactam drugs, we introduce two metrics that capture (i) the average susceptibility of an allelic variant of a drug target to any available drug in a given panel (“variant vulnerability”), and (ii) the average applicability of a drug (or mixture) across allelic variants of a drug target (“drug applicability”). Finally, we (iii) disentangle the quality and magnitude of interactions between loci in the drug target and the seven drug environments in terms of their mutation by mutation by environment (G x G x E) interactions, offering mechanistic insight into the variant variability and drug applicability metrics. Summarizing, we propose that our framework can be applied to other datasets and pathogen-drug systems to understand which pathogen variants in a clinical setting are the most concerning (low variant vulnerability), and which drugs in a panel are most likely to be effective in an infection defined by standing genetic variation in the pathogen drug target (high drug applicability).}, author={Guerrero, Rafael F. and Dorji, Tandin and Harris, Ra’Mal M. and Shoulders, Matthew D. and Ogbunugafor, C. Brandon}, year={2023}, month={Nov} }
 @article{yan_blue_truong_zhang_guerrero_liu_honigberg_parry_mcneil_mercer_et al._2023, title={Genetic Associations with Dynamic Placental Proteins Identify Causal Biomarkers for Hypertension in Pregnancy}, url={https://doi.org/10.1101/2023.05.25.23290460}, DOI={10.1101/2023.05.25.23290460}, abstractNote={ABSTRACT}, author={Yan, Qi and Blue, Nathan R. and Truong, Buu and Zhang, Yu and Guerrero, Rafael F. and Liu, Nianjun and Honigberg, Michael C. and Parry, Samuel and McNeil, Rebecca B. and Mercer, Brian M. and et al.}, year={2023}, month={May} }
 @article{honigberg_truong_khan_xiao_bhatta_vy_guerrero_schuermans_selvaraj_patel_et al._2023, title={Polygenic prediction of preeclampsia and gestational hypertension}, volume={5}, ISSN={["1546-170X"]}, DOI={10.1038/s41591-023-02374-9}, abstractNote={Preeclampsia and gestational hypertension are common pregnancy complications associated with adverse maternal and child outcomes. Current tools for prediction, prevention and treatment are limited. Here we tested the association of maternal DNA sequence variants with preeclampsia in 20,064 cases and 703,117 control individuals and with gestational hypertension in 11,027 cases and 412,788 control individuals across discovery and follow-up cohorts using multi-ancestry meta-analysis. Altogether, we identified 18 independent loci associated with preeclampsia/eclampsia and/or gestational hypertension, 12 of which are new (for example, MTHFR-CLCN6, WNT3A, NPR3, PGR and RGL3), including two loci (PLCE1 and FURIN) identified in the multitrait analysis. Identified loci highlight the role of natriuretic peptide signaling, angiogenesis, renal glomerular function, trophoblast development and immune dysregulation. We derived genome-wide polygenic risk scores that predicted preeclampsia/eclampsia and gestational hypertension in external cohorts, independent of clinical risk factors, and reclassified eligibility for low-dose aspirin to prevent preeclampsia. Collectively, these findings provide mechanistic insights into the hypertensive disorders of pregnancy and have the potential to advance pregnancy risk stratification.}, journal={NATURE MEDICINE}, author={Honigberg, Michael C. and Truong, Buu and Khan, Raiyan R. and Xiao, Brenda and Bhatta, Laxmi and Vy, Ha My T. and Guerrero, Rafael F. and Schuermans, Art and Selvaraj, Margaret Sunitha and Patel, Aniruddh P. and et al.}, year={2023}, month={May} }
 @article{yan_guerrero_khan_surujnarine_wapner_hahn_raja_sallebaouissi_grobman_simhan_et al._2023, title={Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b}, url={https://doi.org/10.1101/2023.05.25.23290500}, DOI={10.1101/2023.05.25.23290500}, abstractNote={Abstract}, author={Yan, Qi and Guerrero, Rafael F. and Khan, Raiyan R. and Surujnarine, Andy A. and Wapner, Ronald J. and Hahn, Matthew W. and Raja, Anita and SallebAouissi, Ansaf and Grobman, William A. and Simhan, Hyagriv and et al.}, year={2023}, month={Jun} }
 @article{yan_guerrero_khan_surujnarine_wapner_hahn_raja_salleb-aouissi_grobman_simhan_et al._2023, title={Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b}, volume={225}, ISSN={["1943-2631"]}, DOI={10.1093/genetics/iyad151}, abstractNote={Abstract}, number={2}, journal={GENETICS}, author={Yan, Qi and Guerrero, Rafael F. and Khan, Raiyan R. and Surujnarine, Andy A. and Wapner, Ronald J. and Hahn, Matthew W. and Raja, Anita and Salleb-Aouissi, Ansaf and Grobman, William A. and Simhan, Hyagriv and et al.}, year={2023}, month={Oct} }
 @article{pagel_chu_ramola_guerrero_chung_parry_reddy_silver_steller_yee_et al._2022, title={Association of Genetic Predisposition and Physical Activity With Risk of Gestational Diabetes in Nulliparous Women}, volume={5}, ISSN={["2574-3805"]}, DOI={10.1001/jamanetworkopen.2022.29158}, abstractNote={Key Points Question Are genetic predisposition to diabetes and physical activity in early pregnancy cooperatively associated with risk of gestational diabetes (GD) among nulliparous women? Findings In this cohort study of 3533 women, a high polygenic risk score (PRS) and low level of physical activity were associated with increased risk of GD. The estimated odds for participants with high PRS and low level of physical activity was 3.4 but was near or less than the baseline level of 1.0 with either low PRS or high activity. Meaning These findings suggest that physical activity in early pregnancy is associated with reduced risk of GD and reversal of excess risk in genetically predisposed individuals, and PRS may have utility in identifying women for targeted interventions.}, number={8}, journal={JAMA NETWORK OPEN}, author={Pagel, Kymberleigh A. and Chu, Hoyin and Ramola, Rashika and Guerrero, Rafael F. and Chung, Judith H. and Parry, Samuel and Reddy, Uma M. and Silver, Robert M. and Steller, Jonathan G. and Yee, Lynn M. and et al.}, year={2022}, month={Aug} }
 @article{guerrero_khan_wapner_hahn_raja_salleb-aouissi_grobman_simhan_silver_chung_et al._2022, title={Genetic Polymorphisms Associated with Adverse Pregnancy Outcomes in Nulliparas}, url={https://doi.org/10.1101/2022.02.28.22271641}, DOI={10.1101/2022.02.28.22271641}, abstractNote={ABSTRACT}, author={Guerrero, Rafael F. and Khan, Raiyan R. and Wapner, Ronald J. and Hahn, Matthew W. and Raja, Anita and Salleb-Aouissi, Ansaf and Grobman, William A. and Simhan, Hyagriv and Silver, Robert and Chung, Judith H. and et al.}, year={2022}, month={Mar} }
 @article{honigberg_truong_khan_xiao_bhatta_vy_guerrero_schuermans_selvaraj_patel_et al._2022, title={Genome-wide meta-analysis identifies novel maternal risk variants and enables polygenic prediction of preeclampsia and gestational hypertension}, url={https://doi.org/10.1101/2022.11.30.22282929}, DOI={10.1101/2022.11.30.22282929}, abstractNote={Abstract}, author={Honigberg, Michael C. and Truong, Buu and Khan, Raiyan R. and Xiao, Brenda and Bhatta, Laxmi and Vy, Thi Ha and Guerrero, Rafael F. and Schuermans, Art and Selvaraj, Margaret Sunitha and Patel, Aniruddh P. and et al.}, year={2022}, month={Dec} }
 @article{pagel_chu_ramola_guerrero_chung_parry_reddy_silver_steller_yee_et al._2022, title={The influence of genetic predisposition and physical activity on risk of Gestational Diabetes Mellitus in the nuMoM2b cohort}, url={https://doi.org/10.1101/2022.03.08.22271868}, DOI={10.1101/2022.03.08.22271868}, abstractNote={Abstract}, author={Pagel, Kymberleigh A. and Chu, Hoyin and Ramola, Rashika and Guerrero, Rafael F. and Chung, Judith H. and Parry, Samuel and Reddy, Uma M. and Silver, Robert M. and Steller, Jonathan G. and Yee, Lynn M. and et al.}, year={2022}, month={Mar} }
 @article{wu_haak_anderson_hahn_moyle_guerrero_2021, title={Inferring the Genetic Basis of Sex Determination from the Genome of a Dioecious Nightshade}, volume={38}, ISSN={["1537-1719"]}, url={https://doi.org/10.1093/molbev/msab089}, DOI={10.1093/molbev/msab089}, abstractNote={Abstract}, number={7}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, publisher={Oxford University Press (OUP)}, author={Wu, Meng and Haak, David C. and Anderson, Gregory J. and Hahn, Matthew W. and Moyle, Leonie C. and Guerrero, Rafael F.}, editor={Purugganan, MichaelEditor}, year={2021}, month={Jul}, pages={2946–2957} }
 @article{stamboulian_guerrero_hahn_radivojac_2020, title={The ortholog conjecture revisited: the value of orthologs and paralogs in function prediction}, volume={36}, ISSN={["1460-2059"]}, DOI={10.1093/bioinformatics/btaa468}, abstractNote={Abstract}, journal={BIOINFORMATICS}, author={Stamboulian, Moses and Guerrero, Rafael F. and Hahn, Matthew W. and Radivojac, Predrag}, year={2020}, month={Jul}, pages={219–226} }
 @article{kasak_hunter_udani_bakolitsa_hu_adhikari_babbi_casadio_gough_guerrero_et al._2019, title={CAGI SickKids challenges: Assessment of phenotype and variant predictions derived from clinical and genomic data of children with undiagnosed diseases}, volume={40}, url={https://doi.org/10.1002/humu.23874}, DOI={10.1002/humu.23874}, abstractNote={Whole‐genome sequencing (WGS) holds great potential as a diagnostic test. However, the majority of patients currently undergoing WGS lack a molecular diagnosis, largely due to the vast number of undiscovered disease genes and our inability to assess the pathogenicity of most genomic variants. The CAGI SickKids challenges attempted to address this knowledge gap by assessing state‐of‐the‐art methods for clinical phenotype prediction from genomes. CAGI4 and CAGI5 participants were provided with WGS data and clinical descriptions of 25 and 24 undiagnosed patients from the SickKids Genome Clinic Project, respectively. Predictors were asked to identify primary and secondary causal variants. In addition, for CAGI5, groups had to match each genome to one of three disorder categories (neurologic, ophthalmologic, and connective), and separately to each patient. The performance of matching genomes to categories was no better than random but two groups performed significantly better than chance in matching genomes to patients. Two of the ten variants proposed by two groups in CAGI4 were deemed to be diagnostic, and several proposed pathogenic variants in CAGI5 are good candidates for phenotype expansion. We discuss implications for improving in silico assessment of genomic variants and identifying new disease genes.}, number={9}, journal={Human Mutation}, publisher={Wiley}, author={Kasak, Laura and Hunter, Jesse M. and Udani, Rupa and Bakolitsa, Constantina and Hu, Zhiqiang and Adhikari, Aashish N. and Babbi, Giulia and Casadio, Rita and Gough, Julian and Guerrero, Rafael F. and et al.}, year={2019}, month={Sep}, pages={1373–1391} }
 @article{guerrero_scarpino_rodrigues_hartl_ogbunugafor_2019, title={Proteostasis Environment Shapes Higher-Order Epistasis Operating on Antibiotic Resistance}, volume={212}, url={https://doi.org/10.1534/genetics.119.302138}, DOI={10.1534/genetics.119.302138}, abstractNote={Abstract}, number={2}, journal={Genetics}, publisher={Genetics Society of America}, author={Guerrero, Rafael F. and Scarpino, Samuel V. and Rodrigues, João V. and Hartl, Daniel L. and Ogbunugafor, C. Brandon}, year={2019}, month={Jun}, pages={565–575} }
 @article{berrio_guerrero_aglyamova_okhovat_matz_phelps_2018, title={Complex selection on a regulator of social cognition: Evidence of balancing selection, regulatory interactions and population differentiation in the prairie vole Avpr1a locus}, url={https://doi.org/10.1111/mec.14455}, DOI={10.1111/mec.14455}, abstractNote={Abstract}, journal={Molecular Ecology}, author={Berrio, Alejandro and Guerrero, Rafael F. and Aglyamova, Galina V. and Okhovat, Mariam and Matz, Mikhail V. and Phelps, Steven M.}, year={2018}, month={Jan} }
 @article{guerrero_hahn_2018, title={Quantifying the risk of hemiplasy in phylogenetic inference}, volume={115}, url={https://doi.org/10.1073/pnas.1811268115}, DOI={10.1073/pnas.1811268115}, abstractNote={Significance}, number={50}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Guerrero, Rafael F. and Hahn, Matthew W.}, year={2018}, month={Dec}, pages={12787–12792} }
 @article{guerrero_muir_josway_moyle_2017, title={Pervasive antagonistic interactions among hybrid incompatibility loci}, volume={13}, DOI={10.1371/journal.pgen.1006817}, abstractNote={Species barriers, expressed as hybrid inviability and sterility, are often due to epistatic interactions between divergent loci from two lineages. Theoretical models indicate that the strength, direction, and complexity of these genetic interactions can strongly affect the expression of interspecific reproductive isolation and the rates at which new species evolve. Nonetheless, empirical analyses have not quantified the frequency with which loci are involved in interactions affecting hybrid fitness, and whether these loci predominantly interact synergistically or antagonistically, or preferentially involve loci that have strong individual effects on hybrid fitness. We systematically examined the prevalence of interactions between pairs of short chromosomal regions from one species (Solanum habrochaites) co-introgressed into a heterospecific genetic background (Solanum lycopersicum), using lines containing pairwise combinations of 15 chromosomal segments from S. habrochaites in the background of S. lycopersicum (i.e., 95 double introgression lines). We compared the strength of hybrid incompatibility (either pollen sterility or seed sterility) expressed in each double introgression line to the expected additive effect of its two component single introgressions. We found that epistasis was common among co-introgressed regions. Interactions for hybrid dysfunction were substantially more prevalent in pollen fertility compared to seed fertility phenotypes, and were overwhelmingly antagonistic (i.e., double hybrids were less unfit than expected from additive single introgression effects). This pervasive antagonism is expected to attenuate the rate at which hybrid infertility accumulates among lineages over time (i.e., giving diminishing returns as more reproductive isolation loci accumulate), as well as decouple patterns of accumulation of sterility loci and hybrid incompatibility phenotypes. This decoupling effect might explain observed differences between pollen and seed fertility in their fit to theoretical predictions of the accumulation of isolation loci, including the ‘snowball’ effect.}, number={6}, journal={PLOS Genetics}, publisher={Public Library of Science (PLoS)}, author={Guerrero, Rafael F. and Muir, Christopher D. and Josway, Sarah and Moyle, Leonie C.}, editor={Köhler, ClaudiaEditor}, year={2017}, month={Jun}, pages={e1006817} }
 @article{guerrero_hahn_2017, title={Speciation as a Sieve for Ancestral Polymorphism}, volume={8}, url={https://doi.org/10.1111/mec.14290}, DOI={10.1111/mec.14290}, abstractNote={Abstract}, journal={Molecular Ecology}, publisher={Wiley-Blackwell}, author={Guerrero, Rafael F. and Hahn, Matthew W.}, year={2017}, month={Aug} }
 @article{marais_guerrero_lasky_scarpino_2017, title={Topological features of a gene co-expression network predict patterns of natural diversity in environmental response}, volume={284}, url={https://doi.org/10.1098/rspb.2017.0914}, DOI={10.1098/rspb.2017.0914}, abstractNote={
            Molecular interactions affect the evolution of complex traits. For instance, adaptation may be constrained by pleiotropic or epistatic effects, both of which can be reflected in the structure of molecular interaction networks. To date, empirical studies investigating the role of molecular interactions in phenotypic evolution have been idiosyncratic, offering no clear patterns. Here, we investigated the network topology of genes putatively involved in local adaptation to two abiotic stressors—drought and cold—in
            Arabidopsis thaliana
            . Our findings suggest that the gene-interaction topologies for both cold and drought stress response are non-random, with genes that show genetic variation in drought expression response (eGxE) being significantly more peripheral and cold response genes being significantly more central than genes which do not show GxE. We suggest that the observed topologies reflect different constraints on the genetic pathways involved in environmental response. The approach presented here may inform predictive models linking genetic variation in molecular signalling networks with phenotypic variation, specifically traits involved in environmental response.
          }, number={1856}, journal={Proceedings of the Royal Society B: Biological Sciences}, publisher={The Royal Society}, author={Marais, David L. Des and Guerrero, Rafael F. and Lasky, Jesse R. and Scarpino, Samuel V.}, year={2017}, month={Jun}, pages={20170914} }
 @article{transcriptomic analysis links gene expression to unilateral pollen-pistil reproductive barriers._2017, volume={4}, url={http://europepmc.org/abstract/med/28438120}, DOI={10.1186/s12870-017-1032-4}, abstractNote={Unilateral incompatibility (UI) is an asymmetric reproductive barrier that unidirectionally prevents gene flow between species and/or populations. UI is characterized by a compatible interaction between partners in one direction, but in the reciprocal cross fertilization fails, generally due to pollen tube rejection by the pistil. Although UI has long been observed in crosses between different species, the underlying molecular mechanisms are only beginning to be characterized. The wild tomato relative Solanum habrochaites provides a unique study system to investigate the molecular basis of this reproductive barrier, as populations within the species exhibit both interspecific and interpopulation UI. Here we utilized a transcriptomic approach to identify genes in both pollen and pistil tissues that may be key players in UI.We confirmed UI at the pollen-pistil level between a self-incompatible population and a self-compatible population of S. habrochaites. A comparison of gene expression between pollinated styles exhibiting the incompatibility response and unpollinated controls revealed only a small number of differentially expressed transcripts. Many more differences in transcript profiles were identified between UI-competent versus UI-compromised reproductive tissues. A number of intriguing candidate genes were highly differentially expressed, including a putative pollen arabinogalactan protein, a stylar Kunitz family protease inhibitor, and a stylar peptide hormone Rapid ALkalinization Factor. Our data also provide transcriptomic evidence that fundamental processes including reactive oxygen species (ROS) signaling are likely key in UI pollen-pistil interactions between both populations and species.Gene expression analysis of reproductive tissues allowed us to better understand the molecular basis of interpopulation incompatibility at the level of pollen-pistil interactions. Our transcriptomic analysis highlighted specific genes, including those in ROS signaling pathways that warrant further study in investigations of UI. To our knowledge, this is the first report to identify candidate genes involved in unilateral barriers between populations within a species.}, journal={BMC plant biology}, year={2017}, month={Apr} }
 @article{guerrero_posto_moyle_hahn_2016, title={Genome-wide patterns of regulatory divergence revealed by introgression lines}, volume={70}, DOI={10.1111/evo.12875}, abstractNote={Understanding the genetic basis for changes in transcriptional regulation is an important aspect of understanding phenotypic evolution. Using interspecific introgression lines, we infer the mechanisms of divergence in genome-wide patterns of gene expression between the nightshades Solanum pennellii and S. lycopersicum (domesticated tomato). We find that cis- and frans-regulatory changes have had qualitatively similar contributions to divergence in this clade, unlike results from other systems. Additionally, expression data from four tissues (shoot apex, ripe fruit, pollen, and seed) suggest that introgressed regions in these hybrid lines tend to be down-regulated, while background (non-introgressed) genes tend to be up-regulated. Finally, we find no evidence for an association between the magnitude of differential expression in NILs and previously determined sterility phenotypes. Our results contradict previous predictions of the predominant role of cis- over frans-regulatory divergence between species, and do not support a major role for gross genome-wide misregulation in reproductive isolation between these species.}, number={3}, journal={Evolution}, publisher={Wiley-Blackwell}, author={Guerrero, Rafael F. and Posto, Amanda L. and Moyle, Leonie C. and Hahn, Matthew W.}, year={2016}, month={Feb}, pages={696–706} }
 @article{pease_guerrero_sherman_hahn_moyle_2016, title={Molecular mechanisms of postmating prezygotic reproductive isolation uncovered by transcriptome analysis}, volume={25}, url={https://doi.org/10.1111/mec.13679}, DOI={10.1111/mec.13679}, abstractNote={Abstract}, number={11}, journal={Molecular Ecology}, publisher={Wiley}, author={Pease, James B. and Guerrero, Rafael F. and Sherman, Natasha A. and Hahn, Matthew W. and Moyle, Leonie C.}, year={2016}, month={Jun}, pages={2592–2608} }
 @article{guerrero_kirkpatrick_2014, title={LOCAL ADAPTATION AND THE EVOLUTION OF CHROMOSOME FUSIONS}, volume={68}, DOI={10.1111/evo.12481}, abstractNote={We use forward and coalescent models of population genetics to study chromosome fusions that reduce the recombination between two locally adapted loci. Under a continent–island model, a fusion spreads and reaches a polymorphic equilibrium when it causes recombination between locally adapted alleles to be less than their selective advantage. In contrast, fusions in a two‐deme model always spread; whether it reaches a polymorphic equilibrium or becomes fixed depends on the relative recombination rates of fused homozygotes and heterozygotes. Neutral divergence around fusion polymorphisms is markedly increased, showing peaks at the point of fusion and at the locally adapted loci. Local adaptation could explain the evolution of many of chromosome fusions, which are some of the most common chromosome rearrangements in nature.}, number={10}, journal={Evolution}, publisher={Wiley-Blackwell}, author={Guerrero, Rafael F. and Kirkpatrick, Mark}, year={2014}, month={Aug}, pages={2747–2756} }
 @article{matrix inversions for chromosomal inversions: a method to construct summary statistics in complex coalescent models_2014, DOI={10.1016/j.tpb.2014.07.005}, abstractNote={Chromosomal inversions allow genetic divergence of locally adapted populations by reducing recombination between chromosomes with different arrangements. While patterns of genetic variation within inverted regions are increasingly documented, inferential methods are largely missing to analyze such data. Previous work has provided expectations for coalescence patterns of neutral sites linked to an inversion polymorphism in two locally adapted populations. Here, we define a method to construct summary statistics in such complex population structure models. Under a scenario of selection on the inversion breakpoints, we first construct estimators of the migration rate between the two habitats, and of the recombination rate of a nucleotide site between the two inversion backgrounds. Next, we analyze the disequilibrium between two sites within an inversion and provide an estimator of the distinct recombination rate between these two sites in homokaryotypes and heterokaryotypes. These estimators should be suitable summary statistics for simulation-based methods that can handle the complex dependences in the data.}, journal={Theoretical Population Biology}, year={2014}, month={Nov} }
 @article{signatures of sex-antagonistic selection on recombining sex chromosomes._2014, volume={6}, url={http://europepmc.org/abstract/med/24578352}, DOI={10.1534/genetics.113.156026}, abstractNote={Abstract}, journal={Genetics}, year={2014}, month={Jun} }
 @article{strong reinforcing selection in a texas wildflower._2014, volume={9}, url={http://europepmc.org/abstract/med/25155503}, DOI={10.1016/j.cub.2014.07.027}, abstractNote={Reinforcement, the process of increased reproductive isolation due to selection against hybrids, is an important mechanism by which natural selection contributes to speciation [1Howard D.J. Reinforcement: origin, dynamics and fate of an evolutionary hypothesis.in: Harrison R.G. Hybrid Zones and the Evolutionary Process. Oxford University Press, New York1993: 46-69Google Scholar]. Empirical studies suggest that reinforcement has generated reproductive isolation in many taxa (reviewed in [2Hopkins R. Reinforcement in plants.New Phytol. 2013; 197: 1095-1103Crossref PubMed Scopus (122) Google Scholar, 3Ortiz-Barrientos D. Grealy A. Nosil P. The genetics and ecology of reinforcement: implications for the evolution of prezygotic isolation in sympatry and beyond.Ann. N Y Acad. Sci. 2009; 1168: 156-182Crossref PubMed Scopus (114) Google Scholar, 4Servedio M.R. Noor M.A.F. The role of reinforcement in speciation: theory and data.Annu. Rev. Ecol. Evol. Syst. 2003; 34: 339-364Crossref Scopus (694) Google Scholar]), and theoretical work shows it can act under broad selective conditions [5Kirkpatrick M. Ravigné V. Speciation by natural and sexual selection: models and experiments.Am. Nat. 2002; 159: S22-S35Crossref PubMed Google Scholar, 6Kirkpatrick M. Reinforcement and divergence under assortative mating.Proc. Biol. Sci. 2000; 267: 1649-1655Crossref PubMed Scopus (135) Google Scholar, 7Kirkpatrick M. Reinforcement during ecological speciation.Proc. Biol. Sci. 2001; 268: 1259-1263Crossref PubMed Scopus (73) Google Scholar, 8Kirkpatrick M. Servedio M.R. The reinforcement of mating preferences on an island.Genetics. 1999; 151: 865-884PubMed Google Scholar, 9Liou L.W. Price T.D. Speciation by reinforcement of premating isolation.Evolution. 1994; 48: 1451-1459Crossref Google Scholar, 10Bank C. Hermisson J. Kirkpatrick M. Can reinforcement complete speciation?.Evolution. 2012; 66: 229-239Crossref PubMed Scopus (40) Google Scholar, 11Servedio M.R. The evolution of premating isolation: local adaptation and natural and sexual selection against hybrids.Evolution. 2004; 58: 913-924Crossref PubMed Scopus (106) Google Scholar]. However, the strength of selection driving reinforcement has never been measured in nature. Here, we quantify the strength of reinforcing selection in the Texas wildflower Phlox drummondii using a strategy that weds a population genetic model with field data. Reinforcement in this system is caused by variation in two loci that affect flower color [12Hopkins R. Rausher M.D. Identification of two genes causing reinforcement in the Texas wildflower Phlox drummondii.Nature. 2011; 469: 411-414Crossref PubMed Scopus (135) Google Scholar]. We quantify sharp clines in flower color where this species comes into contact with its congener, Phlox cuspidata. We develop a spatially explicit population genetic model for these clines based on the known genetics of flower color. We fit our model to the data using likelihood, and we searched parameter space using Markov chain Monte Carlo methods. We find that selection on flower color genes generated by reinforcement is exceptionally strong. Our findings demonstrate that natural selection can play a decisive role in the evolution of reproductive isolation through the process of reinforcement.}, journal={Current biology : CB}, year={2014}, month={Sep} }
 @article{a sequential coalescent algorithm for chromosomal inversions._2013, volume={9}, url={http://europepmc.org/abstract/med/23632894}, DOI={10.1038/hdy.2013.38}, abstractNote={Chromosomal inversions are common in natural populations and are believed to be involved in many important evolutionary phenomena, including speciation, the evolution of sex chromosomes and local adaptation. While recent advances in sequencing and genotyping methods are leading to rapidly increasing amounts of genome-wide sequence data that reveal interesting patterns of genetic variation within inverted regions, efficient simulation methods to study these patterns are largely missing. In this work, we extend the sequential Markovian coalescent, an approximation to the coalescent with recombination, to include the effects of polymorphic inversions on patterns of recombination. Results show that our algorithm is fast, memory-efficient and accurate, making it feasible to simulate large inversions in large populations for the first time. The SMC algorithm enables studies of patterns of genetic variation (for example, linkage disequilibria) and tests of hypotheses (using simulation-based approaches) that were previously intractable.}, journal={Heredity}, year={2013}, month={Sep} }
 @article{coalescent patterns for chromosomal inversions in divergent populations._2012, volume={2}, url={http://europepmc.org/abstract/med/22201172}, DOI={10.1098/rstb.2011.0246}, abstractNote={Chromosomal inversions allow genetic divergence of locally adapted populations by reducing recombination between chromosomes with different arrangements. Divergence between populations (or hybridization between species) is expected to leave signatures in the neutral genetic diversity of the inverted region. Quantitative expectations for these patterns, however, have not been obtained. Here, we develop coalescent models of neutral sites linked to an inversion polymorphism in two locally adapted populations. We consider two scenarios of local adaptation: selection on the inversion breakpoints and selection on alleles inside the inversion. We find that ancient inversion polymorphisms cause genetic diversity to depart dramatically from neutral expectations. Other situations, however, lead to patterns that may be difficult to detect; important determinants are the age of the inversion and the rate of gene flux between arrangements. We also study inversions under genetic drift, finding that they produce patterns similar to locally adapted inversions of intermediate age. Our results are consistent with empirical observations, and provide the foundation for quantitative analyses of the roles that inversions have played in speciation.}, journal={Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, year={2012}, month={Feb} }
 @article{cryptic recombination in the ever-young sex chromosomes of hylid frogs._2012, volume={10}, url={http://europepmc.org/abstract/med/22901240}, DOI={10.1111/j.1420-9101.2012.02591.x}, abstractNote={Abstract}, journal={Journal of evolutionary biology}, year={2012}, month={Oct} }
 @article{ayala_guerrero_kirkpatrick_2012, title={REPRODUCTIVE ISOLATION AND LOCAL ADAPTATION QUANTIFIED FOR A CHROMOSOME INVERSION IN A MALARIA MOSQUITO}, volume={67}, DOI={10.1111/j.1558-5646.2012.01836.x}, abstractNote={Chromosome inversions have long been thought to be involved in speciation and local adaptation. We have little quantitative information, however, about the effects that inversion polymorphisms have on reproductive isolation and viability. Here we provide the first estimates from any organism for the total amount of reproductive isolation associated with an inversion segregating in natural populations. We sampled chromosomes from 751 mosquitoes of the malaria vector Anopheles funestus along a 1421 km transect in Cameroon that traverses savannah, highland, and rainforest ecological zones. We then developed a series of population genetic models that account for selection, migration, and assortative mating, and fit the models to the data using likelihood. Results from the best‐fit models suggest there is strong local adaptation, with relative viabilities of homozygotes ranging from 25% to 130% compared to heterozygotes. Viabilities vary qualitatively between regions: the inversion is underdominant in the savannah, whereas in the highlands it is overdominant. The inversion is also implicated in strong assortative mating. In the savannah, the two homozygote forms show 92% reproductive isolation, suggesting that this one inversion can generate most of the genetic barriers needed for speciation.}, number={4}, journal={Evolution}, publisher={Wiley-Blackwell}, author={Ayala, Diego and Guerrero, Rafael F. and Kirkpatrick, Mark}, year={2012}, month={Nov}, pages={946–958} }
 @article{about par: the distinct evolutionary dynamics of the pseudoautosomal region._2011, volume={9}, url={http://europepmc.org/abstract/med/21962971}, DOI={10.1016/j.tig.2011.05.001}, abstractNote={Sex chromosomes differ from other chromosomes in the striking divergence they often show in size, structure, and gene content. Not only do they possess genes controlling sex determination that are restricted to either the X or Y (or Z or W) chromosomes, but in many taxa they also include recombining regions. In these 'pseudoautosomal regions' (PARs), sequence homology is maintained by meiotic pairing and exchange in the heterogametic sex. PARs are unique genomic regions, exhibiting some features of autosomes, but they are also influenced by their partial sex linkage. Here we review the distribution and structure of PARs among animals and plants, the theoretical predictions concerning their evolutionary dynamics, the reasons for their persistence, and the diversity and content of genes that reside within them. It is now clear that the evolution of the PAR differs in important ways from that of genes in either the non-recombining regions of sex chromosomes or the autosomes.}, journal={Trends in genetics : TIG}, year={2011}, month={Sep} }
 @article{patterns of neutral genetic variation on recombining sex chromosomes._2010, volume={4}, url={http://europepmc.org/abstract/med/20124026}, DOI={10.1534/genetics.109.113555}, abstractNote={Abstract}, journal={Genetics}, year={2010}, month={Apr} }