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‣ Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology

Delport, Wayne; Poon, Art F. Y.; Frost, Simon D. W.; Kosakovsky Pond, Sergei L.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
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Summary: Datamonkey is a popular web-based suite of phylogenetic analysis tools for use in evolutionary biology. Since the original release in 2005, we have expanded the analysis options to include recently developed algorithmic methods for recombination detection, evolutionary fingerprinting of genes, codon model selection, co-evolution between sites, identification of sites, which rapidly escape host-immune pressure and HIV-1 subtype assignment. The traditional selection tools have also been augmented to include recent developments in the field. Here, we summarize the analyses options currently available on Datamonkey, and provide guidelines for their use in evolutionary biology.

‣ Emergence, hierarchy and top-down causation in evolutionary biology

Okasha, Samir
Fonte: The Royal Society Publicador: The Royal Society
Tipo: Artigo de Revista Científica
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The concept of emergence and the related notion of ‘downward causation’ have arisen in numerous branches of science, and have also been extensively discussed in philosophy. Here, I examine emergence and downward causation in relation to evolutionary biology. I focus on the old, but ongoing discussion in evolutionary biology over the ‘levels of selection’ question: which level(s) of the biological hierarchy natural selection acts at, e.g. the gene, individual, group or species level? The concept of emergence has arisen in the levels-of-selection literature as a putative way of distinguishing between ‘true’ selection at a higher level from cases where selection acts solely at the lower level but has effects that percolate up the biological hierarchy, generating the appearance of higher level selection. At first blush, this problem seems to share a common structure with debates about emergence in other areas, but closer examination shows that it turns on issues that are sui generis to biology.

‣ Evolutionary biology and the avoidance of antimicrobial resistance

Read, Andrew F; Huijben, Silvie
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em /02/2009 Português
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Evolutionary biologists have largely left the search for solutions to the drug resistance crisis to biomedical scientists, physicians, veterinarians and public health specialists. We believe this is because the vast majority of professional evolutionary biologists consider the evolutionary science of drug resistance to be conceptually uninteresting. Using malaria as case study, we argue that it is not. We review examples of evolutionary thinking that challenge various fallacies dominating antimalarial therapy, and discuss open problems that need evolutionary insight. These problems are unlikely to be resolved by biomedical scientists ungrounded in evolutionary biology. Involvement by evolutionary biologists in the science of drug resistance requires no intellectual compromises: the problems are as conceptually challenging as they are important.

‣ A Careful Look at Binding Site Reorganization in the even-skipped Enhancers of Drosophila and Sepsids

Hare, Emily E.; Eisen, Michael B.; Peterson, Brant K.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Organismic and Evolutionary Biology

‣ Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation

Hare, Emily E.; Iyer, Venky N.; Meier, Rudolf; Eisen, Michael B.; Peterson, Brant K.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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The gene expression pattern specified by an animal regulatory sequence is generally viewed as arising from the particular arrangement of transcription factor binding sites it contains. However, we demonstrate here that regulatory sequences whose binding sites have been almost completely rearranged can still produce identical outputs. We sequenced the even-skipped locus from six species of scavenger flies (Sepsidae) that are highly diverged from the model species Drosophila melanogaster, but share its basic patterns of developmental gene expression. Although there is little sequence similarity between the sepsid eve enhancers and their well-characterized D. melanogaster counterparts, the sepsid and Drosophila enhancers drive nearly identical expression patterns in transgenic D. melanogaster embryos. We conclude that the molecular machinery that connects regulatory sequences to the transcription apparatus is more flexible than previously appreciated. In exploring this diverse collection of sequences to identify the shared features that account for their similar functions, we found a small number of short (20–30 bp) sequences nearly perfectly conserved among the species. These highly conserved sequences are strongly enriched for pairs of overlapping or adjacent binding sites. Together...

‣ Functional Evolution of cis-Regulatory Modules at a Homeotic Gene in Drosophila

Ho, Margaret C. W.; Goetz, Sara E.; Schiller, Benjamin J.; Bae, Esther; Tran, Diana A.; Shur, Andrey S.; Rau, Christoph; Celniker, Susan E.; Drewell, Robert A.; Johnsen, Holly; Allen, John M; Bender, Welcome W.; Fisher, William W.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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It is a long-held belief in evolutionary biology that the rate of molecular evolution for a given DNA sequence is inversely related to the level of functional constraint. This belief holds true for the protein-coding homeotic (Hox) genes originally discovered in Drosophila melanogaster. Expression of the Hox genes in Drosophila embryos is essential for body patterning and is controlled by an extensive array of cis-regulatory modules (CRMs). How the regulatory modules functionally evolve in different species is not clear. A comparison of the CRMs for the Abdominal-B gene from different Drosophila species reveals relatively low levels of overall sequence conservation. However, embryonic enhancer CRMs from other Drosophila species direct transgenic reporter gene expression in the same spatial and temporal patterns during development as their D. melanogaster orthologs. Bioinformatic analysis reveals the presence of short conserved sequences within defined CRMs, representing gap and pair-rule transcription factor binding sites. One predicted binding site for the gap transcription factor KRUPPEL in the IAB5 CRM was found to be altered in Superabdominal (Sab) mutations. In Sab mutant flies, the third abdominal segment is transformed into a copy of the fifth abdominal segment. A model for KRUPPEL-mediated repression at this binding site is presented. These findings challenge our current understanding of the relationship between sequence evolution at the molecular level and functional activity of a CRM. While the overall sequence conservation at Drosophila CRMs is not distinctive from neighboring genomic regions...

‣ Fetal Programming and Fetal Psychology

Ellison, Peter T.
Fonte: John Wiley & Sons, Ltd. Publicador: John Wiley & Sons, Ltd.
Tipo: Artigo de Revista Científica
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The introduction of the ‘fetal programming hypothesis’, first in epidemiology, subsequently in a broad range of disciplines concerned with developmental biology, has generated new interest in phenotypic plasticity, the mechanisms that govern it, and its place in evolutionary biology. A number of epidemiological studies link small size at birth, assumed to be a consequence of constrained prenatal energy availability, with adverse effects on the risk of chronic diseases later in life. The cluster of chronic diseases associated with the metabolic syndrome and alterations of glucose metabolism are particularly implicated. Recent evidence suggests that epigenetic modification of gene expression affecting the hypothalamic-pituitary-adrenal (HPA) axis may be involved in these effects. In animal studies epigenetic alteration of HPA axis activity and responsiveness is associated with changes in adult behaviour and stress responsiveness. The potential for similar effects to contribute to psychological and psychiatric outcomes in humans has been explored in a number of contexts, including famine exposure, observed covariance with birth weight, and prenatal dexamethasone treatment of fetuses at risk of congenital adrenal hyperplasia. While fetal programming effects have now been widely demonstrated across species and human populations...

‣ Terrestrialization, Miniaturization and Rates of Diversification in African Puddle Frogs (Anura: Phrynobatrachidae)

Lawson, Lucinda; Loader, Simon P.; Zimkus, Breda Marie; Hanken, James
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Terrestrialization, the evolution of non-aquatic oviposition, and miniaturization, the evolution of tiny adult body size, are recurring trends in amphibian evolution, but the relationships among the traits that characterize these phenomena are not well understood. Furthermore, these traits have been identified as possible “key innovations” that are predicted to increase rates of speciation in those lineages in which they evolve. We examine terrestrialization and miniaturization in sub-Saharan puddle frogs (Phrynobatrachidae) in a phylogenetic context to investigate the relationship between adaptation and diversification through time. We use relative dating techniques to ascertain if character trait shifts are associated with increased diversification rates, and we evaluate the likelihood that a single temporal event can explain the evolution of those traits. Results indicate alternate reproductive modes evolved independently in Phrynobatrachus at least seven times, including terrestrial deposition of eggs and terrestrial, non-feeding larvae. These shifts towards alternate reproductive modes are not linked to a common temporal event. Contrary to the “key innovations” hypothesis, clades that exhibit alternate reproductive modes have lower diversification rates than those that deposit eggs aquatically. Adult habitat...

‣ Repeated, Selection-Driven Genome Reduction of Accessory Genes in Experimental Populations

Lee, Ming-Chun; Marx, Christopher J
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Genome reduction has been observed in many bacterial lineages that have adapted to specialized environments. The extreme genome degradation seen for obligate pathogens and symbionts appears to be dominated by genetic drift. In contrast, for free-living organisms with reduced genomes, the dominant force is proposed to be direct selection for smaller, streamlined genomes. Most variation in gene content for these free-living species is of “accessory” genes, which are commonly gained as large chromosomal islands that are adaptive for specialized traits such as pathogenicity. It is generally unclear, however, whether the process of accessory gene loss is largely driven by drift or selection. Here we demonstrate that selection for gene loss, and not a shortened genome, per se, drove massive, rapid reduction of accessory genes. In just 1,500 generations of experimental evolution, 80% of populations of Methylobacterium extorquens AM1 experienced nearly parallel deletions removing up to 10% of the genome from a megaplasmid present in this strain. The absence of these deletion events in a mutation accumulation experiment suggested that selection, rather than drift, has dominated the process. Reconstructing these deletions confirmed that they were beneficial in their selective regimes...

‣ Expression and Putative Function of Innate Immunity Genes under In Situ Conditions in the Symbiotic Hydrothermal Vent Tubeworm Ridgeia piscesae

Nyholm, Spencer V.; Song, Pengfei; Dang, Jeanne; Bunce, Corey; Girguis, Peter R.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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The relationships between hydrothermal vent tubeworms and sulfide-oxidizing bacteria have served as model associations for understanding chemoautotrophy and endosymbiosis. Numerous studies have focused on the physiological and biochemical adaptations that enable these symbioses to sustain some of the highest recorded carbon fixation rates ever measured. However, far fewer studies have explored the molecular mechanisms underlying the regulation of host and symbiont interactions, specifically those mediated by the innate immune system of the host. To that end, we conducted a series of studies where we maintained the tubeworm, Ridgeia piscesae, in high-pressure aquaria and examined global and quantitative changes in gene expression via high-throughput transcriptomics and quantitative real-time PCR (qPCR). We analyzed over 32,000 full-length expressed sequence tags as well as 26 Mb of transcript sequences from the trophosome (the organ that houses the endosymbiotic bacteria) and the plume (the gas exchange organ in contact with the free-living microbial community). R. piscesae maintained under conditions that promote chemoautotrophy expressed a number of putative cell signaling and innate immunity genes, including pattern recognition receptors (PRRs)...

‣ A Phylogenomic Approach to Vertebrate Phylogeny Supports a Turtle-Archosaur Affinity and a Possible Paraphyletic Lissamphibia

Fong, Jonathan J.; Brown, Jeremy M.; Fujita, Matthew; Boussau, Bastien
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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In resolving the vertebrate tree of life, two fundamental questions remain: 1) what is the phylogenetic position of turtles within amniotes, and 2) what are the relationships between the three major lissamphibian (extant amphibian) groups? These relationships have historically been difficult to resolve, with five different hypotheses proposed for turtle placement, and four proposed branching patterns within Lissamphibia. We compiled a large cDNA/EST dataset for vertebrates (75 genes for 129 taxa) to address these outstanding questions. Gene-specific phylogenetic analyses revealed a great deal of variation in preferred topology, resulting in topologically ambiguous conclusions from the combined dataset. Due to consistent preferences for the same divergent topologies across genes, we suspected systematic phylogenetic error as a cause of some variation. Accordingly, we developed and tested a novel statistical method that identifies sites that have a high probability of containing biased signal for a specific phylogenetic relationship. After removing putatively biased sites, support emerged for a sister relationship between turtles and either crocodilians or archosaurs, as well as for a caecilian-salamander sister relationship within Lissamphibia...

‣ Inferring Predator Behavior from Attack Rates on Prey-Replicas That Differ in Conspicuousness

Stuart, Yoel Eli; Dappen, Nathan; Losin, Neil
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Behavioral ecologists and evolutionary biologists have long studied how predators respond to prey items novel in color and pattern. Because a predatory response is influenced by both the predator’s ability to detect the prey and a post-detection behavioral response, variation among prey types in conspicuousness may confound inference about post-prey-detection predator behavior. That is, a relatively high attack rate on a given prey type may result primarily from enhanced conspicuousness and not predators’ direct preference for that prey. Few studies, however, account for such variation in conspicuousness. In a field experiment, we measured predation rates on clay replicas of two aposematic forms of the poison dart frog Dendrobates pumilio, one novel and one familiar, and two cryptic controls. To ask whether predators prefer or avoid a novel aposematic prey form independently of conspicuousness differences among replicas, we first modeled the visual system of a typical avian predator. Then, we used this model to estimate replica contrast against a leaf litter background to test whether variation in contrast alone could explain variation in predator attack rate. We found that absolute predation rates did not differ among color forms. Predation rates relative to conspicuousness did...

‣ Genetic Surveillance Detects Both Clonal and Epidemic Transmission of Malaria following Enhanced Intervention in Senegal

Daniels, Rachel Fath; Chang, Hsiao-Han; Séne, Papa Diogoye; Park, Danny C.; Neafsey, Daniel Edward; Schaffner, Stephen; Hamilton, Elizabeth Julia; Lukens, Amanda Kathleen; Van Tyne, Daria Natalie; Mboup, Souleymane; Sabeti, Pardis Christine; Ndiaye, Daou
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically identical parasite strains, coincident with increased deployment of malaria control interventions and decreased malaria deaths. Parasite genotypes in some cases persisted clonally across dry seasons. The increase in frequency of genetically identical parasite strains corresponded with decrease in the probability of multiple infections. Further, these observations support evidence of both clonal and epidemic population structures. These data provide the first evidence of a temporal correlation between the appearance of identical parasite types and increased malaria control efforts in Africa, which here included distribution of insecticide treated nets (ITNs), use of rapid diagnostic tests (RDTs) for malaria detection, and deployment of artemisinin combination therapy (ACT). Our results imply that genetic surveillance can be used to evaluate the effectiveness of disease control strategies and assist a rational global malaria eradication campaign.; Human Evolutionary Biology; Organismic and Evolutionary Biology

‣ Evolution after Introduction of a Novel Metabolic Pathway Consistently Leads to Restoration of Wild-Type Physiology

Carroll, Sean; Marx, Christopher J
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Organisms cope with physiological stressors through acclimatizing mechanisms in the short-term and adaptive mechanisms over evolutionary timescales. During adaptation to an environmental or genetic perturbation, beneficial mutations can generate numerous physiological changes: some will be novel with respect to prior physiological states, while others might either restore acclimatizing responses to a wild-type state, reinforce them further, or leave them unchanged. We examined the interplay of acclimatizing and adaptive responses at the level of global gene expression in Methylobacterium extorquens AM1 engineered with a novel central metabolism. Replacing central metabolism with a distinct, foreign pathway resulted in much slower growth than wild-type. After 600 generations of adaptation, however, eight replicate populations founded from this engineered ancestor had improved up to 2.5-fold. A comparison of global gene expression in wild-type, engineered, and all eight evolved strains revealed that the vast majority of changes during physiological adaptation effectively restored acclimatizing processes to wild-type expression states. On average, 93% of expression perturbations from the engineered strain were restored, with 70% of these occurring in perfect parallel across all eight replicate populations. Novel changes were common but typically restricted to one or a few lineages...

‣ Potential use of low-copy nuclear genes in DNA barcoding: a comparison with plastid genes in two Hawaiian plant radiations

Pillon, Yohan; Johansen, Jennifer; Sakishima, Tomoko; Chamala, Srikar; Barbazuk, W Brad; Roalson, Eric H.; Price, Donald K.; Stacy, Elizabeth A.
Fonte: BioMed Central (BMC Evolutionary Biology); BioMed Central (BMC Evolutionary Biology) Publicador: BioMed Central (BMC Evolutionary Biology); BioMed Central (BMC Evolutionary Biology)
Tipo: mixed material
Publicado em //2013 Português
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Publication of this article was funded in part bu the University of Florida Open-Access publishing Fund. In addition, requestors receiving funding through the UFOAP project are expected to submit a post-review, final draft of the article to UF 's institutional repository, IR@UF, (www.uflib.ufl.edu/UFir) at the time of funding. The institutional Repository at the University of Florida community, with research, news, outreach, and educational materials. ; Pillon et al. BMC Evolutionary Biology 2013, 13:35 http://www.biomedcentral.com/1471-2148/13/35; Pages 1-10; doi:10.1186/1471-2148-13-35 Cite this article as: Pillon et al.: Potential use of low-copy nuclear genes in DNA barcoding: a comparison with plastid genes in two Hawaiian plant radiations. BMC Evolutionary Biology 2013 13:35.

‣ Phylogenetic analysis of symbionts in feather-feeding lice of the genus Columbicola: evidence for repeated symbiont replacements

Smith, Wendy A.; Oaksen, Kelly F.; Johnson, Kevin P.; Reed, David L.; Carter, Tamar; Smith, Kari L.; Koga, Ryuichi
Fonte: BioMed Central (BMC Evolutionary Biology); BioMed Central (BMC Evolutionary Biology) Publicador: BioMed Central (BMC Evolutionary Biology); BioMed Central (BMC Evolutionary Biology)
Tipo: mixed material
Publicado em //2013 Português
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Publication of this article was funded in part by the University of Florida Open Access publishing Fund. In addition, requestors receiving funding through the UFOAP project are expected to submit a post-review, final draft of the article to UF's institutional repository, IR@UF, (www.uflib.ufl.edu/UFir) at the time of funding. The institutional Repository at the University of Florida community, with research, news, outreach, and educational materials.; Smith et al. BMC Evolutionary Biology 2013, 13:109 http://www.biomedcentral.com/1471-2148/13/109; Pages 1-15; doi:10.1186/1471-2148-13-109 Cite this article as: Smith et al.: Phylogenetic analysis of symbionts in feather-feeding lice of the genus Columbicola: evidence for repeated symbiont replacements. BMC Evolutionary Biology 2013 13:109.

‣ Probing entry inhibitors' activity on HIV and development of new fusion inhibitors : integrating evolutionary biology with virology

Borrego, Pedro José Vieira Borga Martins, 1980-
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Tese de Doutorado
Publicado em //2011 Português
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Tese de doutoramento, Farmácia (Microbiologia), Universidade de Lisboa, Faculdade de Farmácia, 2011; The general aims of this thesis were: 1) to examine the C2, V3 and C3 envelope regions ofHIV-1 and HIV-2 at the molecular, evolutionary and structural levels; 2) to compare HIV-1and HIV-2 susceptibility to entry inhibitors and assess their potential value in HIV-2therapy; 3) to produce a new fusion inhibitor peptide using evolutionary biology basedstrategies.In the first study (Chapter 2), HIV-1 and HIV-2 were compared at the molecular,evolutionary and structural levels in the C2, V3 and C3 envelope regions. We identifiedsignificant structural and functional constrains to the diversification and evolution of C2,V3 and C3 in the HIV-2 envelope but not in HIV-1. In particular, we found that V3 in HIV-2is less exposed and more conserved than in HIV-1, suggesting fundamental differences inthe biology and infection of these viruses as well as in their susceptibility to entryinhibitors.In the second study (Chapter 3) we measured the baseline susceptibility of HIV-1 and HIV-2primary isolates to different fusion inhibitors and coreceptor antagonists, includingenfuvirtide (T-20) and maraviroc (MVC). MVC inhibited HIV-2 R5 variants at significantlyhigher IC90 concentrations than HIV-1 variants. Moreover...

‣ Indirect Evolution of Hybrid Lethality due to Linkage with Selected Locus in Mimulus guttatus

Wright, Kevin M.; Lloyd, Deborah; Lowry, David B.; Macnair, Mark R.; Willis, John H.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Most species are superbly and intricately adapted to the environments in which they live. Adaptive evolution by natural selection is the primary force shaping biological diversity. Differences between closely related species in ecologically selected characters such as habitat preference, reproductive timing, courtship behavior, or pollinator attraction may prevent interbreeding in nature, causing reproductive isolation. But does ecological adaptation cause reproductive incompatibilities such as hybrid sterility or lethality? Although several genes causing hybrid incompatibilities have been identified, there is intense debate over whether the genes that contribute to ecological adaptations also cause hybrid incompatibilities. Thirty years ago, a genetic study of local adaptation to copper mine soils in the wildflower Mimulus guttatus identified a locus that appeared to cause copper tolerance and hybrid lethality in crosses to other populations. But do copper tolerance and hybrid lethality have the same molecular genetic basis? Here we show, using high-resolution genome mapping, that copper tolerance and hybrid lethality are not caused by the same gene but are in fact separately controlled by two tightly linked loci. We further show that selection on the copper tolerance locus indirectly caused the hybrid incompatibility allele to go to high frequency in the copper mine population because of hitchhiking. Our results provide a new twist on Darwin's original supposition that hybrid incompatibilities evolve as an incidental by-product of ordinary adaptation to the environment.; Organismic and Evolutionary Biology

‣ Short Lesson Plan Associated with Increased Acceptance of Evolutionary Theory and Potential Change in Three Alternate Conceptions of Macroevolution in Undergraduate Students

Abraham, Joel K.; Perez, Kathryn E.; Downey, Nicholas; Herron, Jon C.; Meir, Eli
Fonte: American Society for Cell Biology Publicador: American Society for Cell Biology
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
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Undergraduates commonly harbor alternate conceptions about evolutionary biology; these alternate conceptions often persist, even after intensive instruction, and may influence acceptance of evolution. We interviewed undergraduates to explore their alternate conceptions about macroevolutionary patterns and designed a 2-h lesson plan to present evidence that life has evolved. We identified three alternate conceptions during our interviews: that newly derived traits would be more widespread in extant species than would be ancestral traits, that evolution proceeds solely by anagenesis, and that lineages must become more complex over time. We also attempted to measure changes in the alternate conceptions and levels of acceptance of evolutionary theory in biology majors and nonmajors after exposure to the lesson plan. The instrument used to assess understanding had flaws, but our results are suggestive of mixed effects: we found a reduction in the first alternate conception, no change in the second, and reinforcement of the third. We found a small, but significant, increase in undergraduate acceptance of evolutionary theory in two trials of the lesson plan (Cohen's d effect sizes of 0.51 and 0.19). These mixed results offer guidance on how to improve the lesson and show the potential of instructional approaches for influencing acceptance of evolution.

‣ Cancer research meets evolutionary biology

Pepper, John W; Scott Findlay, C; Kassen, Rees; Spencer, Sabrina L; Maley, Carlo C
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em /02/2009 Português
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There is increasing evidence that Darwin's theory of evolution by natural selection provides insights into the etiology and treatment of cancer. On a microscopic scale, neoplastic cells meet the conditions for evolution by Darwinian selection: cell reproduction with heritable variability that affects cell survival and replication. This suggests that, like other areas of biological and biomedical research, Darwinian theory can provide a general framework for understanding many aspects of cancer, including problems of great clinical importance. With the availability of raw molecular data increasing rapidly, this theory may provide guidance in translating data into understanding and progress. Several conceptual and analytical tools from evolutionary biology can be applied to cancer biology. Two clinical problems may benefit most from the application of Darwinian theory: neoplastic progression and acquired therapeutic resistance. The Darwinian theory of cancer has especially profound implications for drug development, both in terms of explaining past difficulties, and pointing the way toward new approaches. Because cancer involves complex evolutionary processes, research should incorporate both tractable (simplified) experimental systems...