@article{caicedo_richards_ehrenreich_purugganan_2009, title={Complex Rearrangements Lead to Novel Chimeric Gene Fusion Polymorphisms at the Arabidopsis thaliana MAF2-5 Flowering Time Gene Cluster}, volume={26}, ISSN={["1537-1719"]}, DOI={10.1093/molbev/msn300}, abstractNote={Tandem gene clusters of multigene families are rearrangement hotspots and may be a major source of novel gene formation. Here, we report on a molecular population genetic analysis of the MAF2-5 gene cluster of the model plant species, Arabidopsis thaliana. The MAF2-5 genes are a MADS-box multigene family cluster spanning approximately 24 kbp on chromosome 5. We find heterogeneous evolutionary dynamics among these genes, all of which are closely related to the floral repressor, FLC, and are believed to play a role in the control of flowering time in A. thaliana. Low levels of nonsynonymous single nucleotide polymorphism (SNP) observed for MAF4 and MAF5 suggest purifying selection and conservation of function. In contrast, high levels of nonsynonymous SNPs, insertion-deletion, and rearrangements are observed for MAF2 and MAF3, including novel gene fusions that persist as a moderate-frequency polymorphism in A. thaliana. These fused genes, involving MAF2 and portions of MAF3, are expressed, resulting in the production of chimeric, alternatively spliced transcripts of MAF2. Association studies support a correlation between the described MAF2-MAF3 gene rearrangements and flowering time variation in the species. The finding that complex rearrangements within gene clusters, such as those observed for MAF2, might play a role in the generation of ecologically important phenotypic variation, emphasize the need for emerging high throughput genotyping and sequencing techniques to correctly reconstruct gene chimeras and other complex polymorphisms.}, number={3}, journal={MOLECULAR BIOLOGY AND EVOLUTION}, author={Caicedo, Ana L. and Richards, Christina and Ehrenreich, Ian M. and Purugganan, Michael D.}, year={2009}, month={Mar}, pages={699–711} } @article{shimizu_reininga_caicedo_mays_moore_olsen_ruzsa_coop_bustamante_purugganan_2008, title={Darwinian selection on a selfing locus (vol 306, pg 2081, 2004)}, volume={320}, number={5873}, journal={Science}, author={Shimizu, K. K. and Reininga, J. M. and Caicedo, A. L. and Mays, C. A. and Moore, R. C. and Olsen, K. M. and Ruzsa, S. and Coop, G. and Bustamante, C. D. and Purugganan, M. D.}, year={2008}, pages={176–176} } @article{korves_schmid_caicedo_mays_stinchcombe_purugganan_schmitt_2007, title={Fitness effects associated with the major flowering time gene FRIGIDA in Arabidopsis thaliana in the field}, volume={169}, ISSN={["1537-5323"]}, DOI={10.1086/513111}, abstractNote={To date, the effect of natural selection on candidate genes underlying complex traits has rarely been studied experimentally, especially under ecologically realistic conditions. Here we report that the effect of selection on the flowering time gene FRIGIDA (FRI) reverses depending on the season of germination and allelic variation at the interacting gene FLOWERING LOCUS C (FLC). In field studies of 136 European accessions of Arabidopsis thaliana, accessions with putatively functional FRI alleles had higher winter survival in one FLC background in a fall‐germinating cohort, but accessions with deletion null FRI alleles had greater seed production in the other FLC background in a spring‐germinating cohort. Consistent with FRI’s role in flowering, selection analyses suggest that the difference in winter survival can be attributed to time to bolting. However, in the spring cohort, the fitness difference was associated with rosette size. Our analyses also reveal that controlling for population structure with estimates of inferred ancestry and a geographical restriction was essential for detecting fitness associations. Overall, our results suggest that the combined effects of seasonally varying selection and epistasis could explain the maintenance of variation at FRI and, more generally, may be important in the evolution of genes underlying complex traits.}, number={5}, journal={AMERICAN NATURALIST}, author={Korves, Tonia M. and Schmid, Karl J. and Caicedo, Ana L. and Mays, Charlotte and Stinchcombe, John R. and Purugganan, Michael D. and Schmitt, Johanna}, year={2007}, pages={E141–E157} } @article{caicedo_williamson_hernandez_boyko_fledel-alon_york_polato_olsen_nielsen_mccouch_et al._2007, title={Genome-wide patterns of nucleotide polymorphism in domesticated rice}, volume={3}, ISSN={["1553-7404"]}, DOI={10.1371/journal.pgen.0030163}, abstractNote={Domesticated Asian rice (Oryza sativa) is one of the oldest domesticated crop species in the world, having fed more people than any other plant in human history. We report the patterns of DNA sequence variation in rice and its wild ancestor, O. rufipogon, across 111 randomly chosen gene fragments, and use these to infer the evolutionary dynamics that led to the origins of rice. There is a genome-wide excess of high-frequency derived single nucleotide polymorphisms (SNPs) in O. sativa varieties, a pattern that has not been reported for other crop species. We developed several alternative models to explain contemporary patterns of polymorphisms in rice, including a (i) selectively neutral population bottleneck model, (ii) bottleneck plus migration model, (iii) multiple selective sweeps model, and (iv) bottleneck plus selective sweeps model. We find that a simple bottleneck model, which has been the dominant demographic model for domesticated species, cannot explain the derived nucleotide polymorphism site frequency spectrum in rice. Instead, a bottleneck model that incorporates selective sweeps, or a more complex demographic model that includes subdivision and gene flow, are more plausible explanations for patterns of variation in domesticated rice varieties. If selective sweeps are indeed the explanation for the observed nucleotide data of domesticated rice, it suggests that strong selection can leave its imprint on genome-wide polymorphism patterns, contrary to expectations that selection results only in a local signature of variation.}, number={9}, journal={PLOS GENETICS}, author={Caicedo, Ana L. and Williamson, Scott H. and Hernandez, Ryan D. and Boyko, Adam and Fledel-Alon, Adi and York, Thomas L. and Polato, Nicholas R. and Olsen, Kenneth M. and Nielsen, Rasmus and McCouch, Susan R. and et al.}, year={2007}, month={Sep}, pages={1745–1756} } @article{mather_caicedo_polato_olsen_mccouch_purugganan_2007, title={The extent of linkage disequilibrium in rice (Oryza sativa L.)}, volume={177}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.107.079616}, abstractNote={Abstract}, number={4}, journal={GENETICS}, author={Mather, Kristie A. and Caicedo, Ana L. and Polato, Nicholas R. and Olsen, Kenneth M. and McCouch, Susan and Purugganan, Michael D.}, year={2007}, month={Dec}, pages={2223–2232} } @article{olsen_caicedo_polato_mcclung_mccouch_purugganan_2006, title={Selection under domestication: Evidence for a sweep in the rice Waxy genomic region}, volume={173}, ISSN={["1943-2631"]}, DOI={10.1534/genetics.106.056473}, abstractNote={Abstract}, number={2}, journal={GENETICS}, author={Olsen, Kenneth M. and Caicedo, Ana L. and Polato, Nicholas and McClung, Anna and McCouch, Susan and Purugganan, Michael D.}, year={2006}, month={Jun}, pages={975–983} } @article{caicedo_purugganan_2005, title={Comparative plant genomics. Frontiers and prospects}, volume={138}, ISSN={["1532-2548"]}, DOI={10.1104/pp.104.900148}, abstractNote={Comparative methods have long been the cornerstone of studies that draw inferences about function and evolution at various levels of biological organization. The availability of whole-genome sequences as well as other genomic resources (e.g. microarray methods, expressed sequence tag [EST] libraries}, number={2}, journal={PLANT PHYSIOLOGY}, author={Caicedo, AL and Purugganan, MD}, year={2005}, month={Jun}, pages={545–547} } @article{stinchcombe_caicedo_hopkins_mays_boyd_purugganan_schmitt_2005, title={Vernalization sensitivity in Arabidopsis thaliana (brassicaceae): The effects of latitude and FLC variation}, volume={92}, ISSN={["1537-2197"]}, DOI={10.3732/ajb.92.10.1701}, abstractNote={Latitudinal variation in climate is predicted to select for latitudinal differentiation in sensitivity to the environmental cues that signal plants to flower at the appropriate time for a given climate. In Arabidopsis thaliana, flowering is promoted by exposure to cold temperatures (vernalization), and several vernalization pathway loci are known. To test whether natural variation in vernalization sensitivity could account for a previously observed latitudinal cline in flowering time in A. thaliana, we exposed 21 European accessions to 0, 10, 20, or 30 d of vernalization and observed leaf number at flowering under short days in a growth chamber. We observed a significant latitudinal cline in vernalization sensitivity: southern accessions were more sensitive to vernalization than northern accessions. In addition, accessions that were late flowering in the absence of vernalization were more sensitive to vernalization cues. Allelic variation at the flowering time regulatory gene FLC was not associated with mean vernalization sensitivity, but one allele class exhibited greater variance in vernalization sensitivity.}, number={10}, journal={AMERICAN JOURNAL OF BOTANY}, author={Stinchcombe, JR and Caicedo, AL and Hopkins, R and Mays, C and Boyd, EW and Purugganan, MD and Schmitt, J}, year={2005}, month={Oct}, pages={1701–1707} } @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{caicedo_stinchcombe_olsen_schmitt_purugganan_2004, title={Epistatic interaction between Arabidopsis FRI and FLC flowering time genes generates a latitudinal cline in a life history trait}, volume={101}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0406232101}, abstractNote={ Epistatic gene interactions are believed to be a major factor in the genetic architecture of evolutionary diversification. In Arabidopsis thaliana , the FRI and FLC genes mechanistically interact to control flowering time, and here we show that this epistatic interaction also contributes to a latitudinal cline in this life history trait within the species. Two major FLC haplogroups ( FLC A and FLC B ) are associated with flowering time variation in A. thaliana in field conditions, but only in the presence of putatively functional FRI alleles. Significant differences in latitudinal distribution of FLC haplogroups in Eurasia and North Africa also depend on the FRI genotype. There is significant linkage disequilibrium between FRI and FLC despite their location on separate chromosomes. Although no nonsynonymous polymorphisms differentiate FLC A and FLC B , vernalization induces the expression of an alternatively spliced FLC transcript that encodes a variant protein with a radical amino acid replacement associated with the two FLC haplogroups. Numerous polymorphisms differentiating the FLC haplogroups also occur in intronic regions implicated in the regulation of FLC expression. The features of the regulatory gene interaction between FRI and FLC in contributing to the latitudinal cline in A. thaliana flowering time are consistent with the maintenance of this interaction by epistatic selection. These results suggest that developmental genetic pathways and networks provide the molecular basis for epistasis, contributing to ecologically important phenotypic variation in natural populations and to the process of evolutionary diversification. }, number={44}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Caicedo, AL and Stinchcombe, JR and Olsen, KM and Schmitt, J and Purugganan, MD}, year={2004}, month={Nov}, pages={15670–15675} } @article{caicedo_schaal_2004, title={Heterogeneous evolutionary processes affect R gene diversity in natural populations of Solanum pimpinellifolium}, volume={101}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0407899101}, abstractNote={ Resistance ( R ) genes of plants are responsible for pathogen recognition and encode proteins that trigger a cascade of responses when a pathogen invades a plant. R genes are assumed to be under strong selection, but there is limited knowledge of the processes affecting R gene diversity in the wild. In this study, DNA sequence variation of Cf-2 homologs was surveyed in populations of Solanum pimpinellifolium , a wild relative of the cultivated tomato. The Cf-2 locus is involved in resistance to strains of the fungus Cladosporium fulvum . At least 26 different Cf-2 homologs were detected in natural populations of S. pimpinellifolium . These homologs differ by single base pair substitutions as well as indels in regions coding for leucine-rich repeats. Molecular population genetic analyses suggest that natural selection has acted heterogeneously on Cf-2 homologs, with selection against amino acid substitutions occurring in the 5′ portion of the genes, and possible restricted positive selection in the 3′ end. Balancing selection may have maintained haplotypes at the 5′ end of the genes. Limited sequence exchange between genes has also contributed to sequence variation. S. pimpinellifolium individuals differ in the number of Cf-2 homologs they contain, obscuring the relationships of orthology and paralogy. This survey of Cf-2 variation in S. pimpinellifolium illustrates the wealth of R gene diversity that exists in wild plant populations, as well as the complexity of interacting genetic and evolutionary processes that generate such diversity. }, number={50}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Caicedo, AL and Schaal, BA}, year={2004}, month={Dec}, pages={17444–17449} } @article{caicedo_schaal_2004, title={Population structure and phylogeography of Solanum pimpinellifolium inferred from a nuclear gene}, volume={13}, ISSN={["0962-1083"]}, DOI={10.1111/j.1365-294X.2004.02191.x}, abstractNote={Abstract}, number={7}, journal={MOLECULAR ECOLOGY}, author={Caicedo, AL and Schaal, BA}, year={2004}, month={Jul}, pages={1871–1882} }