@article{shin_zhang_wu_2017, title={A Nonparametric survival function estimator via censored kernel quantile regressions}, volume={27}, number={1}, journal={Statistica Sinica}, author={Shin, S. J. and Zhang, H. H. and Wu, Y. C.}, year={2017}, pages={457–478} }
 @article{fraimout_debat_fellous_hufbauer_foucaud_pudlo_marin_price_cattel_chen_et al._2017, title={Deciphering the routes of invasion of Drosophila suzukii by means of ABC random forest}, volume={34}, number={4}, journal={Molecular Biology and Evolution}, author={Fraimout, A. and Debat, V. and Fellous, S. and Hufbauer, R. A. and Foucaud, J. and Pudlo, P. and Marin, J. M. and Price, D. K. and Cattel, J. and Chen, X. and et al.}, year={2017}, pages={980–996} }
 @misc{ritz_noor_singh_2017, title={Variation in Recombination Rate: Adaptive or Not?}, volume={33}, ISSN={["1362-4555"]}, DOI={10.1016/j.tig.2017.03.003}, abstractNote={Rates of meiotic recombination are widely variable both within and among species. However, the functional significance of this variation remains largely unknown. Is the observed within-species variation in recombination rate adaptive? Recent work has revealed new insight into the scale and scope of population-level variation in recombination rate. These data indicate that the magnitude of within-population variation in recombination is similar among taxa. The apparent similarity of the variance in recombination rate among individuals between distantly related species suggests that the relative costs and benefits of recombination that establish the upper and lower bounds may be similar across species. Here we review the current data on intraspecific variation in recombination rate and discuss the molecular and evolutionary costs and benefits of recombination frequency. We place this variation in the context of adaptation and highlight the need for more empirical studies focused on the adaptive value of variation in recombination rate.}, number={5}, journal={TRENDS IN GENETICS}, author={Ritz, Kathryn R. and Noor, Mohamed A. F. and Singh, Nadia D.}, year={2017}, month={May}, pages={364–374} }
 @misc{stone_singh_2016, title={Bias-Variance Tradeoffs in Recombination Rate Estimation}, volume={202}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.115.185561}, abstractNote={Abstract}, number={2}, journal={GENETICS}, author={Stone, Eric A. and Singh, Nadia D.}, year={2016}, month={Feb}, pages={857–859} }
 @article{kuzu_kaye_chery_siggers_yang_dobson_boor_bliss_liu_jogl_et al._2016, title={Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation}, volume={12}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1006120}, abstractNote={Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.}, number={7}, journal={PLOS GENETICS}, author={Kuzu, Guray and Kaye, Emily G. and Chery, Jessica and Siggers, Trevor and Yang, Lin and Dobson, Jason R. and Boor, Sonia and Bliss, Jacob and Liu, Wei and Jogl, Gerwald and et al.}, year={2016}, month={Jul} }
 @article{hunter_robinson_aylor_singh_2016, title={Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females}, volume={6}, ISSN={["2160-1836"]}, DOI={10.1534/g3.116.027631}, abstractNote={Abstract}, number={5}, journal={G3-GENES GENOMES GENETICS}, author={Hunter, Chad M. and Robinson, Matthew C. and Aylor, David L. and Singh, Nadia D.}, year={2016}, month={May}, pages={1409–1416} }
 @article{singh_criscoe_skolfield_kohl_keebaugh_schlenke_2015, title={Fruit flies diversify their offspring in response to parasite infection}, volume={349}, ISSN={["1095-9203"]}, DOI={10.1126/science.aab1768}, abstractNote={Helping the next generation diversify}, number={6249}, journal={SCIENCE}, author={Singh, Nadia D. and Criscoe, Dallas R. and Skolfield, Shelly and Kohl, Kathryn P. and Keebaugh, Erin S. and Schlenke, Todd A.}, year={2015}, month={Aug}, pages={747–750} }
 @article{jackson_nielsen_singh_2015, title={Increased exposure to acute thermal stress is associated with a non-linear increase in recombination frequency and an independent linear decrease in fitness in Drosophila}, volume={15}, ISSN={["1471-2148"]}, DOI={10.1186/s12862-015-0452-8}, abstractNote={Abstract}, journal={BMC EVOLUTIONARY BIOLOGY}, author={Jackson, Savannah and Nielsen, Dahlia M. and Singh, Nadia D.}, year={2015}, month={Aug} }
 @article{dumont_devlin_truempy_miller_singh_2015, title={No Evidence that Infection Alters Global Recombination Rate in House Mice}, volume={10}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0142266}, abstractNote={Recombination rate is a complex trait, with genetic and environmental factors shaping observed patterns of variation. Although recent studies have begun to unravel the genetic basis of recombination rate differences between organisms, less attention has focused on the environmental determinants of crossover rates. Here, we test the effect of one ubiquitous environmental pressure–bacterial infection–on global recombination frequency in mammals. We applied MLH1 mapping to assay global crossover rates in male mice infected with the pathogenic bacterium Borrelia burgdorferi, the causative agent of Lyme Disease, and uninfected control animals. Despite ample statistical power to identify biologically relevant differences between infected and uninfected animals, we find no evidence for a global recombination rate response to bacterial infection. Moreover, broad-scale patterns of crossover distribution, including the number of achiasmate bivalents, are not affected by infection status. Although pathogen exposure can plastically increase recombination in some species, our findings suggest that recombination rates in house mice may be resilient to at least some forms of infection stress. This negative result motivates future experiments with alternative house mouse pathogens to evaluate the generality of this conclusion.}, number={11}, journal={PLoS One}, author={Dumont, Beth L. and Devlin, Amy A. and Truempy, Dana M. and Miller, Jennifer C. and Singh, Nadia D.}, year={2015}, month={Nov} }
 @article{kaitlyn l. o'shea_singh_2015, title={Tetracycline-exposed Drosophila melanogaster males produce fewer offspring but a relative excess of sons}, volume={5}, ISSN={["2045-7758"]}, DOI={10.1002/ece3.1535}, abstractNote={Abstract}, number={15}, journal={ECOLOGY AND EVOLUTION}, author={Kaitlyn L. O'Shea and Singh, Nadia D.}, year={2015}, month={Aug}, pages={3130–3139} }
 @article{hunter_singh_2014, title={DO MALES MATTER? TESTING THE EFFECTS OF MALE GENETIC BACKGROUND ON FEMALE MEIOTIC CROSSOVER RATES IN DROSOPHILA MELANOGASTER}, volume={68}, ISSN={["1558-5646"]}, DOI={10.1111/evo.12455}, abstractNote={Meiotic recombination is a critical genetic process as well as a pivotal evolutionary force. Rates of crossing over are highly variable within and between species, due to both genetic and environmental factors. Early studies in Drosophila implicated female genetic background as a major determinant of crossover rate and recent work has highlighted male genetic background as a possible mediator as well. Our study employed classical genetics to address how female and male genetic backgrounds individually and jointly affect crossover rates. We measured rates of crossing over in a 33 cM region of the Drosophila melanogaster X chromosome using a two‐step crossing scheme exploiting visible markers. In total, we measured crossover rates of 10 inbred lines in a full diallel cross. Our experimental design facilitates measuring the contributions of female genetic background, male genetic background, and female by male genetic background interaction effects on rates of crossing over in females. Our results indicate that although female genetic background significantly affects female meiotic crossover rates in Drosophila, male genetic background and the interaction of female and male genetic backgrounds have no significant effect. These findings thus suggest that male‐mediated effects are unlikely to contribute greatly to variation in recombination rates in natural populations of Drosophila.}, number={9}, journal={EVOLUTION}, author={Hunter, Chad M. and Singh, Nadia D.}, year={2014}, month={Sep}, pages={2718–2726} }
 @article{adrion_kousathanas_pascual_burrack_haddad_bergland_machado_sackton_schlenke_watada_et al._2014, title={Drosophila suzukii: The Genetic Footprint of a Recent, Worldwide Invasion}, volume={31}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msu246}, abstractNote={Native to Asia, the soft-skinned fruit pest Drosophila suzukii has recently invaded the United States and Europe. The eastern United States represents the most recent expansion of their range, and presents an opportunity to test alternative models of colonization history. Here, we investigate the genetic population structure of this invasive fruit fly, with a focus on the eastern United States. We sequenced six X-linked gene fragments from 246 individuals collected from a total of 12 populations. We examine patterns of genetic diversity within and between populations and explore alternative colonization scenarios using approximate Bayesian computation. Our results indicate high levels of nucleotide diversity in this species and suggest that the recent invasions of Europe and the continental United States are independent demographic events. More broadly speaking, our results highlight the importance of integrating population structure into demographic models, particularly when attempting to reconstruct invasion histories. Finally, our simulation results illustrate the general challenge in reconstructing invasion histories using genetic data and suggest that genome-level data are often required to distinguish among alternative demographic scenarios.}, number={12}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Adrion, Jeffrey R. and Kousathanas, Athanasios and Pascual, Marta and Burrack, Hannah J. and Haddad, Nick M. and Bergland, Alan O. and Machado, Heather and Sackton, Timothy B. and Schlenke, Todd A. and Watada, Masayoshi and et al.}, year={2014}, month={Dec}, pages={3148–3163} }
 @article{robinson_stone_singh_2014, title={Population Genomic Analysis Reveals No Evidence for GC-Biased Gene Conversion in Drosophila melanogaster}, volume={31}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/mst220}, abstractNote={Gene conversion is the nonreciprocal exchange of genetic material between homologous chromosomes. Multiple lines of evidence from a variety of taxa strongly suggest that gene conversion events are biased toward GC-bearing alleles. However, in Drosophila, the data have largely been indirect and unclear, with some studies supporting the predictions of a GC-biased gene conversion model and other data showing contradictory findings. Here, we test whether gene conversion events are GC-biased in Drosophila melanogaster using whole-genome polymorphism and divergence data. Our results provide no support for GC-biased gene conversion and thus suggest that this process is unlikely to significantly contribute to patterns of polymorphism and divergence in this system.}, number={2}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Robinson, Matthew C. and Stone, Eric A. and Singh, Nadia D.}, year={2014}, month={Feb}, pages={425–433} }
 @article{singh_koerich_carvalho_clark_2014, title={Positive and Purifying Selection on the Drosophila Y Chromosome}, volume={31}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msu203}, abstractNote={Y chromosomes, with their reduced effective population size, lack of recombination, and male-limited transmission, present a unique collection of constraints for the operation of natural selection. Male-limited transmission may greatly increase the efficacy of selection for male-beneficial mutations, but the reduced effective size also inflates the role of random genetic drift. Together, these defining features of the Y chromosome are expected to influence rates and patterns of molecular evolution on the Y as compared with X-linked or autosomal loci. Here, we use sequence data from 11 genes in 9 Drosophila species to gain insight into the efficacy of natural selection on the Drosophila Y relative to the rest of the genome. Drosophila is an ideal system for assessing the consequences of Y-linkage for molecular evolution in part because the gene content of Drosophila Y chromosomes is highly dynamic, with orthologous genes being Y-linked in some species whereas autosomal in others. Our results confirm the expectation that the efficacy of natural selection at weakly selected sites is reduced on the Y chromosome. In contrast, purifying selection on the Y chromosome for strongly deleterious mutations does not appear to be compromised. Finally, we find evidence of recurrent positive selection for 4 of the 11 genes studied here. Our results thus highlight the variable nature of the mode and impact of natural selection on the Drosophila Y chromosome.}, number={10}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Singh, Nadia D. and Koerich, Leonardo B. and Carvalho, Antonio Bernardo and Clark, Andrew G.}, year={2014}, month={Oct}, pages={2612–2623} }
 @article{singh_stone_aquadro_clark_2013, title={Fine-scale heterogeneity in crossover rate in the garnet-scalloped region of the Drosophila melanogaster X chromosome}, volume={194}, number={2}, journal={Genetics}, author={Singh, N. D. and Stone, E. A. and Aquadro, C. F. and Clark, A. G.}, year={2013}, pages={375–112} }
 @article{singh_jensen_clark_aquadro_2013, title={Inferences of Demography and Selection in an African Population of Drosophila melanogaster}, volume={193}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.112.145318}, abstractNote={Abstract}, number={1}, journal={GENETICS}, author={Singh, Nadia D. and Jensen, Jeffrey D. and Clark, Andrew G. and Aquadro, Charles F.}, year={2013}, month={Jan}, pages={215–228} }
 @article{singh_2012, title={Classical Genetics Meets Next-Generation Sequencing: Uncovering a Genome-Wide Recombination Drosophila melanogaster}, volume={8}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.1003024}, abstractNote={Homologous recombination is a potent genetic force that impacts myriad aspects of genome evolution, from standing levels of nucleotide diversity to the efficacy of natural selection. Coarse-scale recombination rates have long been known to be variable, and much of the early work exploring this variation exploited Drosophila melanogaster as a model [1]–[5]. Yet, determining the scale and scope of intra- and inter-genomic variation in fine-scale recombination rate in Drosophila has proven quite challenging. Fine-scale recombination rate variation is well-described in humans, mice, and yeast, owing in part to techniques such as sperm typing and chromatin immunoprecipitation (for review, see [6]). However, the underlying biology of recombination in Drosophila (including the lack of crossing-over in males, a less punctate recombinational landscape, and the technical difficulties associated with isolating meiotically active cells from the female germline) has precluded the application of these techniques to Drosophila. Moreover, linkage disequilibrium–based approaches, which have enjoyed success in many systems (e.g., [7], [8]), have been hampered in Drosophila until recently by a lack of genome-wide polymorphism data. Though such data are increasingly available, the rapid decay of linkage disequilibrium in Drosophila (e.g., [9]) and possible rampant adaptation (e.g., [10]) may limit the accuracy and efficacy of such approaches. Consequently, previous work exploring fine-scale recombination rate variation in Drosophila has been limited to localized regions or one to two chromosomes (e.g., [11]–[14]). Not to be deterred, Comeron and colleagues couple the power of classical genetics with next-generation sequencing to provide for the first time a high-resolution recombination map of the D. melanogaster genome [15]. Both outcomes of the meiotic recombination process are captured therein: crossovers, which involve reciprocal exchange of genetic material, and noncrossovers, which result in non-reciprocal exchange (Figure 1). 
 
 
 
Figure 1 
 
Schematic representation of the double-strand break (DSB) repair pathway and recombination from Comeron et al. [15]. 
 
 
 
To create this landmark map, Comeron and colleagues generated recombinant advanced intercross lines (RAIL), derived from eight crosses among twelve wild-derived lines. To accurately identify crossover and noncrossover events, haplotype rather than genotype data are required, and Comeron and colleagues use a clever technique to recover haplotypes. RAIL females were individually crossed to D. simulans, and the genomes of single hybrid progeny were sequenced with Illumina technology. Reads mapping to D. simulans were removed bioinformatically to reveal a haploid, meiotically produced D. melanogaster genome. In all, over 100,000 recombination events were localized with kilobase-level precision. 
 
Certainly, this genome-wide recombination map will empower population genetic and molecular evolutionary studies in Drosophila for years to come. However, the sheer number of events catalogued combined with the resolution at which breakpoints could be mapped facilitates a great deal more than quantifying intra- and inter-genomic recombination rate variation. For instance, these data show that although crossover and noncrossover rates are both significantly variable genome-wide, rates of crossing-over are ten times more variable than noncrossover rates. In addition, crossing-over rates are variable among crosses, with the bulk of this variation being driven by regions of increased crossing-over revealed in some crosses but not in others. This is in contrast to previous work suggesting evolutionary conservation of fine-scale recombination rates in Drosophila [14]. Thus, the physical and temporal scales at which fine-scale recombination rates are conserved remain an open question. Another striking finding is that noncrossover and crossover rates are negatively correlated, and moreover, the noncrossover∶crossover ratio correlates negatively with nucleotide diversity. Indeed, the elegant simplicity of this experiment is in stark contrast to the rich complexity of the resulting data, with the results shedding unprecedented light on variation in the Drosophila recombinational landscape and providing new insights into the genetic and molecular bases of this variation. 
 
These data should also allow us to address multiple aspects of the recombination process in an evolutionary context, building on recent advances in other systems. For example, the noncrossover∶crossover ratio has a considerable range, from 0.73∶1 in yeast [16] to 4∶1–15∶1 in humans [17], with D. melanogaster showing a ratio of ∼4∶1 [15]. What determines this ratio? Are different double-strand break resolution pathways (Figure 1) employed to different degrees in different systems, or has divergence in the proteins involved in these pathways generated this variation? Similarly, tract lengths associated with noncrossovers show marked variability, with a median length of 1.8 kb in yeast but much shorter tract lengths in humans (200–1,000 bp) (for review, see [18]) and D. melanogaster (∼500 bp) [15]. Why should such a conserved genetic feature show these differences between taxa? 
 
One particularly interesting evolutionary question concerns the local distribution of crossovers. Recent work in humans and mice implicates histone methyltransferase PRDM9 as a major determinant of recombination hotspots [19]–[21], but several taxa including Drosophila lack a functional copy of this gene [22]. How are crossover locations determined in species lacking PRDM9? Are other histone methyltransferases playing a similar role or are crossover locations determined by other genetic features? With a detailed crossover map in D. melanogaster, we can begin to address this question. One motif associated with crossover locations in D. melanogaster is the simple repeat [CCN]n, which is noteworthy because the repeat [CCG]n and its reverse complement [CGG]n are enriched in dog recombination hotspots [7]. It is intriguing that the canine genome too lacks a functional copy of PRDM9 [7], [22]. Further comparative work exploring crossover distribution and associated sequence motifs in humans, dogs, and Drosophila will enable great progress in uncovering the genetic determinants of crossover distribution in species lacking PRDM9. 
 
These data have further implications yet, particularly for population genetic inference. Traditional population genetic models, such as those aimed at detecting selection by testing for departures from neutral expectation, rely on the fundamental assumption that recombination rate is constant within and between genomes. Violating this assumption may compromise evolutionary inferences. Previous work suggests that positive selection can lead to false inferences of recombination hotspots [23], [24], and it therefore seems reasonable to hypothesize that recombination rate heterogeneity could generate false signatures of positive selection. This hypothesis has not been tested to date, and data presented in this study informs parameter space such that we can investigate this question. Should this assumption adversely affect population genetic inference, these data will be instrumental for developing new models that accommodate recombination rate variation. Such new models have significant potential to enable robust population genetic inference of demography and adaptation.}, number={10}, journal={PLOS GENETICS}, author={Singh, Nadia D.}, year={2012}, month={Oct} }
 @article{connallon_singh_clark_2012, title={Impact of Genetic Architecture on the Relative Rates of X versus Autosomal Adaptive Substitution}, volume={29}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/mss057}, abstractNote={Molecular evolutionary theory predicts that the ratio of autosomal to X-linked adaptive substitution (K(A)/K(x)) is primarily determined by the average dominance coefficient of beneficial mutations. Although this theory has profoundly influenced analysis and interpretation of comparative genomic data, its predictions are based upon two unverified assumptions about the genetic basis of adaptation. The theory assumes that 1) the rate of adaptively driven molecular evolution is limited by the availability of beneficial mutations, and 2) the scaling of evolutionary parameters between the X and the autosomes (e.g., the beneficial mutation rate, and the fitness effect distribution of beneficial alleles, per X-linked versus autosomal locus) is constant across molecular evolutionary timescales. Here, we show that the genetic architecture underlying bouts of adaptive substitution can influence both assumptions, and consequently, the theoretical relationship between K(A)/K(x) and mean dominance. Quantitative predictions of prior theory apply when 1) many genomically dispersed genes potentially contribute beneficial substitutions during individual steps of adaptive walks, and 2) the population beneficial mutation rate, summed across the set of potentially contributing genes, is sufficiently small to ensure that adaptive substitutions are drawn from new mutations rather than standing genetic variation. Current research into the genetic basis of adaptation suggests that both assumptions are plausibly violated. We find that the qualitative positive relationship between mean dominance and K(A)/K(x) is relatively robust to the specific conditions underlying adaptive substitution, yet the quantitative relationship between dominance and K(A)/K(x) is quite flexible and context dependent. This flexibility may partially account for the puzzlingly variable X versus autosome substitution patterns reported in the empirical evolutionary genomics literature. The new theory unites the previously separate analysis of adaptation using new mutations versus standing genetic variation and makes several useful predictions about the interaction between genetic architecture, evolutionary genetic constraints, and effective population size in determining the ratio of adaptive substitution between autosomal and X-linked genes.}, number={8}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Connallon, Tim and Singh, Nadia D. and Clark, Andrew G.}, year={2012}, month={Aug}, pages={1933–1942} }
 @article{singh_shaw_2012, title={On the scent of pleiotropy}, volume={109}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.1118531109}, abstractNote={From bird songs to the great horn of the rhinoceros beetle, the gaudiest, and possibly most frequent, displays among animals occur in the context of sexual communication and reproduction. Testimony to the evolutionary importance of sexual communication is the recurring observation that signals are “tuned” to perception within species, and vice versa. The importance of sexual communication in coordinating mating interactions and determining successful outcomes has suggested to many that the mate recognition system of a species will be forever hovering around an optimally designed volley of information. A commonly held idea for how this coadaptation between signal and response might arise and be maintained has been dubbed the “coevolution” model, wherein genetically independent signal and response traits are mutually adjusted via selection on each component. An alternative model, often referred to as “genetic coupling,” surfaces regularly and hypothesizes a common genetic basis for both the signal and response. Under this model, both traits share genetic components. The appealing possibility that pleiotropic control assists the coordination of signaler and receiver traits, particularly during episodes of divergence and speciation, was fixed long ago within the scientific imagination (1–3) despite little evidence for it. The work presented in PNAS by Bousquet et al. (4) builds the best case to date for genetic coupling between signaler and receiver traits in sexual communication.}, number={1}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Singh, Nadia D. and Shaw, Kerry L.}, year={2012}, month={Jan}, pages={5–6} }
 @article{hunter_huang_mackay_singh, title={The genetic architecture of natural variation in recombination rate in Drosophila melanogaster}, volume={12}, number={4}, journal={PLoS Genetics}, author={Hunter, C. M. and Huang, W. and Mackay, T. F. C. and Singh, N. D.} }