@article{myers_casals_gauthier_hamdan_keebler_boyko_bustamante_piton_spiegelman_henrion_et al._2011, title={A population genetic approach to mapping neurological disorder genes using deep resequencing}, volume={7}, number={2}, journal={PLoS Genetics}, author={Myers, R. A. and Casals, F. and Gauthier, J. and Hamdan, F. F. and Keebler, J. and Boyko, A. R. and Bustamante, C. D. and Piton, A. M. and Spiegelman, D. and Henrion, E. and et al.}, year={2011} }
 @article{mu_myers_jiang_liu_ricklefs_waisberg_chotivanich_wilairatana_krudsood_white_et al._2010, title={Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs}, volume={42}, number={3}, journal={Nature Genetics}, author={Mu, J. B. and Myers, R. A. and Jiang, H. Y. and Liu, S. F. and Ricklefs, S. and Waisberg, M. and Chotivanich, K. and Wilairatana, P. and Krudsood, S. and White, N. J. and et al.}, year={2010}, pages={268–113} }
 @article{prugnolle_mcgee_keebler_awadalla_2008, title={Selection shapes malaria genomes and drives divergence between pathogens infecting hominids versus rodents}, volume={8}, journal={BMC Evolutionary Biology}, author={Prugnolle, F. and Mcgee, K. and Keebler, J. and Awadalla, P.}, year={2008} }
 @article{mu_awadalla_duan_mcgee_keebler_seydel_mcvean_su_2007, title={Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome}, volume={39}, ISSN={["1546-1718"]}, DOI={10.1038/ng1924}, abstractNote={One goal in sequencing the Plasmodium falciparum genome, the agent of the most lethal form of malaria, is to discover vaccine and drug targets. However, identifying those targets in a genome in which approximately 60% of genes have unknown functions is an enormous challenge. Because the majority of known malaria antigens and drug-resistant genes are highly polymorphic and under various selective pressures, genome-wide analysis for signatures of selection may lead to discovery of new vaccine and drug candidates. Here we surveyed 3,539 P. falciparum genes ( approximately 65% of the predicted genes) for polymorphisms and identified various highly polymorphic loci and genes, some of which encode new antigens that we confirmed using human immune sera. Our collections of genome-wide SNPs ( approximately 65% nonsynonymous) and polymorphic microsatellites and indels provide a high-resolution map (one marker per approximately 4 kb) for mapping parasite traits and studying parasite populations. In addition, we report new antigens, providing urgently needed vaccine candidates for disease control.}, number={1}, journal={NATURE GENETICS}, author={Mu, Jianbing and Awadalla, Philip and Duan, Junhui and McGee, Kate M. and Keebler, Jon and Seydel, Karl and McVean, Gilean A. T. and Su, Xin-zhuan}, year={2007}, month={Jan}, pages={126–130} }
 @article{bockhorst_lu_janes_keebler_gamain_awadalla_su_samudrala_jojica_smith_2007, title={Structural polymorphism and diversifying selection on the pregnancy malaria vaccine candidate VAR2CSA}, volume={155}, ISSN={["0166-6851"]}, DOI={10.1016/j.molbiopara.2007.06.007}, abstractNote={VAR2CSA is the main candidate for a pregnancy malaria vaccine, but vaccine development may be complicated by sequence polymorphism. Here, we obtained partial or full-length var2CSA sequences from 106 parasites and applied novel computational methods and three-dimensional modeling to investigate VAR2CSA geographic variation and selection pressure. Our analysis reveals structural patterns of VAR2CSA sequence variation in which polymorphic sites group into segments of limited diversity. Within these segments, two or three basic types characterize a substantial majority of the parasite samples. Comparison to the primate malaria Plasmodium reichenowi shows that these basic types have ancient origins. Globally, var2CSA genes are comprised of a mosaic of these ancestral polymorphic segments that have recombined extensively between var2CSA alleles. Three-dimensional modeling reveals that polymorphic segments concentrate in flexible loops at characteristic locations in the six VAR2CSA Duffy binding-like (DBL) adhesion domains. Individual DBL domain surfaces have distinct patterns of diversifying selection, suggesting that limited and differing portions of each DBL domain are targeted by host antibody. Since standard phylogenetic tree analysis is inadequate for highly recombining genes like var2CSA, we developed a novel phylogenetic approach that incorporates recombination and tracks new mutations in segment types. In the resulting tree, P. reichenowi is confirmed as an outlier and African and Asian P. falciparum isolates have slightly diverged. These findings validate a new approach to modeling protein evolution in the presence of frequent recombination and provide a clearer understanding of how var gene products function as immunoevasive binding ligands.}, number={2}, journal={MOLECULAR AND BIOCHEMICAL PARASITOLOGY}, author={Bockhorst, Joseph and Lu, Fangli and Janes, Joel H. and Keebler, Jon and Gamain, Benoit and Awadalla, Philip and Su, Xin-zhuan and Samudrala, Ram and Jojica, Nebojsa and Smith, Joseph D.}, year={2007}, month={Oct}, pages={103–112} }
 @article{jackson_watt_gautier_gilchrist_driehaus_graham_keebler_prugnolle_awadalla_forrester_2006, title={A murine specific expansion of the Rhox cluster involved in embryonic stem cell biology is under natural selection}, volume={7}, journal={BMC Genomics}, author={Jackson, M. and Watt, A. J. and Gautier, P. and Gilchrist, D. and Driehaus, J. and Graham, G. J. and Keebler, J. and Prugnolle, F. and Awadalla, P. and Forrester, L. M.}, year={2006} }
 @article{trimnell_kraemer_mukherjee_phippard_janes_flamoe_su_awadalla_smith_2006, title={Global genetic diversity and evolution of var genes associated with placental and severe childhood malaria}, volume={148}, ISSN={["1872-9428"]}, DOI={10.1016/j.molbiopara.2006.03.012}, abstractNote={In Plasmodium falciparum, var genes encode adhesive proteins that are transported to the surface of infected erythrocytes and act as major virulence determinants for infected erythrocyte binding and immune evasion. Var genes are highly diverse and can be classified into five major groups (UpsA, B, C, D, and E). Previous serological studies have suggested that the UpsA var group may contain common antigenic types that have important roles in severe childhood malaria. Here, our analysis found that UpsA vars are highly diverse between 22 world-wide parasite isolates, although they could be grouped into two broad clusters that may be separately recombining. By comparison, orthologs of the UpsA-linked Type 3 var and UpsE-linked var2csa were detected in nearly all parasite isolates, and a var2csa ortholog was also present in a chimpanzee malaria P. reichenowi that diverged from P. falciparum ∼5–7 million years ago. Although the specific function of Type 3 var genes is unknown, var2csa is a leading candidate for a pregnancy associated malaria vaccine. Compared to typical var genes, var2csa is unusually conserved but still had only 54–94% amino acid identity in extracellular binding regions. However, var2csa alleles have extensive gene mosaicism within polymorphic blocks that are shared between world-wide parasite isolates and recognizable in P. rechenowi suggesting a high rate of self–self recombination and an ancient and globally-related pool of var2csa polymorphism. These studies aid our understanding of the evolutionary mechanisms that shape var diversity and will be important to the development of vaccines against pregnancy associated malaria and severe malaria.}, number={2}, journal={MOLECULAR AND BIOCHEMICAL PARASITOLOGY}, author={Trimnell, Adama R. and Kraemer, Susan M. and Mukherjee, Susan and Phippard, David J. and Janes, Joel H. and Flamoe, Eric and Su, Xin-zhuan and Awadalla, Philip and Smith, Joseph D.}, year={2006}, month={Aug}, pages={169–180} }
 @article{carbone_jordan_lyman_harbison_leips_morgan_deluca_awadalla_mackay_2006, title={Phenotypic variation and natural selection at Catsup, a pleiotropic quantitative trait gene in Drosphila}, volume={16}, ISSN={["1879-0445"]}, DOI={10.1016/j.cub.2006.03.051}, abstractNote={Quantitative traits are shaped by networks of pleiotropic genes . To understand the mechanisms that maintain genetic variation for quantitative traits in natural populations and to predict responses to artificial and natural selection, we must evaluate pleiotropic effects of underlying quantitative trait genes and define functional allelic variation at the level of quantitative trait nucleotides (QTNs). Catecholamines up (Catsup), which encodes a negative regulator of tyrosine hydroxylase , the rate-limiting step in the synthesis of the neurotransmitter dopamine, is a pleiotropic quantitative trait gene in Drosophila melanogaster. We used association mapping to determine whether the same or different QTNs at Catsup are associated with naturally occurring variation in multiple quantitative traits. We sequenced 169 Catsup alleles from a single population and detected 33 polymorphisms with little linkage disequilibrium (LD). Different molecular polymorphisms in Catsup are independently associated with variation in longevity, locomotor behavior, and sensory bristle number. Most of these polymorphisms are potentially functional variants in protein coding regions, have large effects, and are not common. Thus, Catsup is a pleiotropic quantitative trait gene, but individual QTNs do not have pleiotropic effects. Molecular population genetic analyses of Catsup sequences are consistent with balancing selection maintaining multiple functional polymorphisms.}, number={9}, journal={CURRENT BIOLOGY}, author={Carbone, Mary Anna and Jordan, Katherine W. and Lyman, Richard F. and Harbison, Susan T. and Leips, Jeff and Morgan, Theodore J. and DeLuca, Maria and Awadalla, Philip and Mackay, Trudy F. C.}, year={2006}, month={May}, pages={912–919} }
 @article{mu_awadalla_duan_mcgee_joy_mcvean_su_2005, title={Recombination hotspots and population structure in Plasmodium falciparum}, volume={3}, ISSN={["1545-7885"]}, DOI={10.1371/journal.pbio.0030335}, abstractNote={Understanding the influences of population structure, selection, and recombination on polymorphism and linkage disequilibrium (LD) is integral to mapping genes contributing to drug resistance or virulence in Plasmodium falciparum. The parasite's short generation time, coupled with a high cross-over rate, can cause rapid LD break-down. However, observations of low genetic variation have led to suggestions of effective clonality: selfing, population admixture, and selection may preserve LD in populations. Indeed, extensive LD surrounding drug-resistant genes has been observed, indicating that recombination and selection play important roles in shaping recent parasite genome evolution. These studies, however, provide only limited information about haplotype variation at local scales. Here we describe the first (to our knowledge) chromosome-wide SNP haplotype and population recombination maps for a global collection of malaria parasites, including the 3D7 isolate, whose genome has been sequenced previously. The parasites are clustered according to continental origin, but alternative groupings were obtained using SNPs at 37 putative transporter genes that are potentially under selection. Geographic isolation and highly variable multiple infection rates are the major factors affecting haplotype structure. Variation in effective recombination rates is high, both among populations and along the chromosome, with recombination hotspots conserved among populations at chromosome ends. This study supports the feasibility of genome-wide association studies in some parasite populations.}, number={10}, journal={PLOS BIOLOGY}, author={Mu, JB and Awadalla, P and Duan, JH and McGee, KM and Joy, DA and McVean, GAT and Su, XZ}, year={2005}, month={Oct}, pages={1734–1741} }
 @article{shimizu_cork_caicedo_mays_moore_olsen_ruzsa_coop_bustamante_awadalla_et al._2004, title={Darwinian selection on a selfing locus (Retracted Article. See vol 320, pg 176, 2008)}, volume={306}, ISSN={["1095-9203"]}, DOI={10.1126/science.1103776}, abstractNote={
            The shift to self-pollination is one of the most prevalent evolutionary transitions in flowering plants. In the selfing plant
            Arabidopsis thaliana
            , pseudogenes at the
            SCR
            and
            SRK
            self-incompatibility loci are believed to underlie the evolution of self-fertilization. Positive directional selection has driven the evolutionary fixation of pseudogene alleles of
            SCR
            , leading to substantially reduced nucleotide variation. Coalescent simulations indicate that this adaptive event may have occurred very recently and is possibly associated with the post-Pleistocene expansion of
            A. thaliana
            from glacial refugia. This suggests that ancillary morphological innovations associated with self-pollination can evolve rapidly after the inactivation of the self-incompatibility response.
          }, number={5704}, journal={SCIENCE}, author={Shimizu, KK and Cork, JM and Caicedo, AL and Mays, CA and Moore, RC and Olsen, KM and Ruzsa, S and Coop, G and Bustamante, CD and Awadalla, P and et al.}, year={2004}, month={Dec}, pages={2081–2084} }
 @article{barbash_awadalla_tarone_2004, title={Functional divergence caused by ancient positive selection of a Drosophila hybrid incompatibility locus}, volume={2}, DOI={10.1371/journal.pbio.0020142}, abstractNote={Interspecific hybrid lethality and sterility are a consequence of divergent evolution between species and serve to maintain the discrete identities of species. The evolution of hybrid incompatibilities has been described in widely accepted models by Dobzhansky and Muller where lineage-specific functional divergence is the essential characteristic of hybrid incompatibility genes. Experimentally tractable models are required to identify and test candidate hybrid incompatibility genes. Several Drosophila melanogaster genes involved in hybrid incompatibility have been identified but none has yet been shown to have functionally diverged in accordance with the Dobzhansky-Muller model. By introducing transgenic copies of the X-linked Hybrid male rescue (Hmr) gene into D. melanogaster from its sibling species D. simulans and D. mauritiana, we demonstrate that Hmr has functionally diverged to cause F1 hybrid incompatibility between these species. Consistent with the Dobzhansky-Muller model, we find that Hmr has diverged extensively in the D. melanogaster lineage, but we also find extensive divergence in the sibling-species lineage. Together, these findings implicate over 13% of the amino acids encoded by Hmr as candidates for causing hybrid incompatibility. The exceptional level of divergence at Hmr cannot be explained by neutral processes because we use phylogenetic methods and population genetic analyses to show that the elevated amino-acid divergence in both lineages is due to positive selection in the distant past—at least one million generations ago. Our findings suggest that multiple substitutions driven by natural selection may be a general phenomenon required to generate hybrid incompatibility alleles.}, number={6}, journal={PLoS Biology}, author={Barbash, D. A. and Awadalla, P. and Tarone, A. M.}, year={2004}, pages={839–848} }
 @article{haydon_bastos_awadalla_2004, title={Low linkage disequilibrium indicative of recombination in foot-and-mouth disease virus gene sequence alignments}, volume={85}, ISSN={["0022-1317"]}, DOI={10.1099/vir.0.19588-0}, abstractNote={We have applied tests for detecting recombination to genes of foot-and-mouth disease virus (FMDV). Our approach estimated summary statistics of linkage disequilibrium (LD), which are sensitive to recombination. Using the genealogical relationships, rate heterogeneity and mutation parameters estimated from individual sets of aligned gene sequences, we simulated matching RNA sequence datasets without recombination. These simulated datasets allowed for recurrent mutations at any site to mimic homoplasy in virus sequence data and allow construction of null distributions for LD parameters expected in the absence of recombination. We tested for recombination in two ways: by comparing LD in observed data with corresponding null distributions obtained from simulated data; and by testing for a negative relationship between observed LD between pairs of polymorphic nucleotide sites and inter-site distance. We applied these tests to six FMDV datasets from four serotypes and found some evidence for recombination in all of them.}, journal={JOURNAL OF GENERAL VIROLOGY}, author={Haydon, DT and Bastos, ADS and Awadalla, P}, year={2004}, month={May}, pages={1095–1100} }