Coestimation of recombination, substitution and molecular adaptation rates by approximate Bayesian computation.

The estimation of parameters in molecular evolution may be biased when some processes are not considered. For example, the estimation of selection at the molecular level using codon-substitution models can have an upward bias when recombination is ignored. Here we address the joint estimation of recombination, molecular adaptation and substitution rates from coding sequences using approximate Bayesian computation (ABC). We describe the implementation of a regression-based strategy for choosing subsets of summary statistics for coding data, and show that this approach can accurately infer recombination allowing for intracodon recombination breakpoints, molecular adaptation and codon substitution rates. We demonstrate that our ABC approach can outperform other analytical methods under a variety of evolutionary scenarios. We also show that although the choice of the codon-substitution model is important, our inferences are robust to a moderate degree of model misspecification. In addition, we demonstrate that our approach can accurately choose the evolutionary model that best fits the data, providing an alternative for when the use of full-likelihood methods is impracticable. Finally, we applied our ABC method to co-estimate recombination, substitution and molecular adaptation rates from 24 published human immunodeficiency virus 1 coding data sets.

A modified bootscan algorithm for automated identification of recombinant sequences and recombination breakpoints.

We have developed a modified BOOTSCAN algorithm that may be used to screen nucleotide sequence alignments for evidence of recombination without prior identification of nonrecombinant reference sequences. The algorithm is fast and includes a Bonferroni corrected statistical test of recombination to circumvent the multiple testing problems encountered when using the BOOTSCAN method to explore alignments for evidence of recombination. Using both simulated and real datasets we demonstrate that the modified algorithm is more powerful than other phylogenetic recombination detection methods and performs almost as well as one of the best substitution distribution recombination detection methods.

Molecular systematics of European Hyalodaphnia: the role of contemporary hybridization in ancient species.

We examined phylogenetic relationships among Daphnia using mitochondrial DNA (mtDNA) sequences from the small subunit ribosomal RNA (12S), cytochrome c oxidase subunit I and nuclear DNA sequences from the first and second internal transcribed spacer representing 1612 base positions. Phylogenetic analyses using several species of the three main Daphnia subgenera, Ctenodaphnia, Hyalodaphnia and Daphnia, revealed that the Hyalodaphnia are a monophyletic sister group of the Daphnia. Most Hyalodaphnia species occur on one continent, whereas only three are found in North America and Europe. Endemicity of species is associated with variation in thermal tolerance and habitat differentiation. Although many species of the Hyalodaphnia are known to hybridize in nature, mtDNA divergence is relatively high ca. 9%) compared to other hybridizing arthropods (ca. 3%). Reproductive isolation in Daphnia seems to evolve significantly slower than genetic isolation. We related these findings to what is known about the ecology and genetics of Daphnia in order to better understand the evolutionary diversification of lineages. The relationship of these data to phylogenetic patterns is discussed in the context of speciation processes in Daphnia.

Mitochondrial DNA phylogeography and population history of the grey wolf canis lupus

The grey wolf (Canis lupus) and coyote (C. latrans) are highly mobile carnivores that disperse over great distances in search of territories and mates. Previous genetic studies have shown little geographical structure in either species. However, population genetic structure is also influenced by past isolation events and population fluctuations during glacial periods. In this study, control region sequence data from a worldwide sample of grey wolves and a more limited sample of coyotes were analysed. The results suggest that fluctuating population sizes during the late Pleistocene have left a genetic signature on levels of variation in both species. Genealogical measures of nucleotide diversity suggest that historical population sizes were much larger in both species and grey wolves were more numerous than coyotes. Currently, about 300 000 wolves and 7 million coyotes exist. In grey wolves, genetic diversity is greater than that predicted from census population size, reflecting recent historical population declines. By contrast, nucleotide diversity in coyotes is smaller than that predicted by census population size, reflecting a recent population expansion following the extirpation of wolves from much of North America. Both species show little partitioning of haplotypes on continental or regional scales. However, a statistical parsimony analysis indicates local genetic structure that suggests recent restricted gene flow.

[The conceptual revolutions about nature as imposed by 20th century physics]. / Las revoluciones conceptuales acerca de la naturaleza impuestas por la física del siglo XX.

A catalogue is offered of the thirteen conceptual--and observational--revolutions which took place in twentieth century Physics, those which should be considered the most revelant for their significance in the scientific and philosophical thought about Nature as established along that century. The are organized in the three areas where they were originated: Relativity, Quantum Physics and Cosmology. Several of these conceptual revolutions appeared in Physics explicitly, while the rest only happened to arise in a latent way. The ones and the others are remarked in this contribution with philosophical expressions and through the world horizon, a perspective which opens in a general manner each revolution to the whole of the scientific and philosophical of the past century.

Natural history of pyuria and microhematuria after prostate surgery.

OBJECTIVE: Urinalysis alterations are common after prostatic surgery. However, time to normalization has not been established. Presence of pyuria and microhematuria can lead to unnecessary diagnostic procedures. The objective of this study is to determine the time to normalization for both parameters. MATERIAL AND METHODS: We reviewed medical records of patients who underwent prostatic surgery without infectious complications during follow-up. We included patients who underwent transurethral resection of the prostate (TURP) with either monopolar or bipolar energy, or open prostatectomy (OP). Kaplan-Meier curves were used to determine the time of persistence of both parameters. ANOVA was used to compare the 3 groups according to the type of surgery. We analyzed the impact of preoperative use of 5-α-reductase inhibitors, and searched for a correlation between the weight of resected tissue and persistence of both parameters. RESULTS: 85 patients were analyzed: 44 underwent monopolar TURP, 27 bipolar TURP, and 14 OP. Persistence of pyuria was significantly longer than microhematuria with a median of 274 days vs. 176 days. Neither the use of monopolar or bipolar energy, nor the use of preoperative 5α-reductase inhibitors affected the persistence time. We found a positive correlation between the resected tissue weight and the persistence of leukocyturia after endoscopic surgery: 23 g was the best cut-off point. CONCLUSIONS: Pyuria persists longer than microhematuria regardless of the type of surgery. There is a correlation between the resected tissue weight and the persistence of pyuria. The presence of pyuria and microhematuria after prostatic surgery is not always a pathological finding.

[Prognostic factors in emphysematous pyelonephritis]. / Factores pronósticos en pielonefritis enfisematosa.

OBJECTIVES: The purpose of this study is to analyze our experience with 18 cases of Emphysematous pyelonephritis (EPN) in a tertiary care center and describe our treatment strategy. MATERIAL AND METHODS: Of 262 patients admitted with acute pyelonephritis, 18 had CT findings of EPN. The Wan and Huang classifications were used. We assessed the clinical, radiological, and therapeutic characteristics of these patients and investigated potential prognostic factors of mortality. RESULTS: Between 2005 and 2010, 17 women and 1 man with EPN were treated. Mean age was 52.4 years. Diabetes was found in 66% and hypertension in 72%. The most common clinical findings were tachycardia (11), fever (11) and flank pain (9); 66% (12) presented with severe sepsis and 2 had septic shock. Acute renal injury developed in 61%. Nine patients were treated exclusively with conservative management; 5 had double J stenting, 3 had CT-guided PCD and 1 required nephrectomy after unsuccessful medical management. Mortality was 11%. Altered consciousness (P=.0001), multiple organ failure (P=.0004), hyperglycemia (P=.003) and elevated leukocyte count (> 20000 K) (P=.01) were more frequent among patients dying from EPN. No difference in mortality was found between patients managed conservatively and those undergoing invasive therapy. CONCLUSIONS: Although rare, EPN should be suspected in patients with multiple comorbidities presenting with severe sepsis. Altered consciousness, multiple organ failure, hyperglycemia and elevated leukocyte count are poor prognosis indicators. Invasive management should be used judiciously and medical treatment can be a safe strategy in selected cases.

Gene expression analysis of clams Ruditapes philippinarum and Ruditapes decussatus following bacterial infection yields molecular insights into pathogen resistance and immunity.

The carpet shell clam (Ruditapes decussatus) and Manila clam (Ruditapes philippinarum), which are cultured bivalve species with important commercial value, are affected by diseases that result in large economic losses. Because the molecular mechanism of the immune response of bivalves, especially clams, is scarce and fragmentary, we have examined all Expressed Sequence Tags (EST) resources available in public databases for these two species in order to increase our knowledge on genes related with the immune function in these animals. After automatic annotation and classification of the 3784 not-annotated ESTs of R. decussatus and 4607 of R. philippinarum found in GenBank, 424 ESTs of R. decussatus and 464 of R. philippinarum were found to be putatively involved in immune response. These were carefully reviewed and reannotated. As a result, 13 immune-related ESTs were selected and studied to compare the immune response of R. decussatus and R. philippinarum following a Vibrio alginolyticus challenge. Quantitative PCR was performed, and the expression of each EST was determined. The results showed that, in R. philippinarum, the immune response seems to be faster than that in R. decussatus. Additionally, expression of NF-κB activating genes in R. decussatus did not seem to be sufficient to promote an immune response after Vibrio infection. R. philippinarum, however, was able to trigger and efficiently regulate the transcriptional activity of NF-κB, even when low expression values were reported.

Selección y evaluación de un estabilizante integrado de gomas sobre las propiedades de calidad en mezclas para helado duro / Selection and evaluation of a stabilizer composed of rubbers on quality properties in mixtures for hard ice cream

Antecedentes: El mercado actual demanda helados con excelentes características de textura y cuerpo, las cuales, en conjunto con el sabor, determinan en gran medida la aceptabilidad de estos. En esta industria es marcada la tendencia hacia el uso de estabilizantes integrados, que potencializan sinergismos entre componentes, obteniendo productos finales de mejor calidad. Objetivos: En el presente trabajo se evalúa el efecto de la adición de una mezcla de goma de algarrobo, goma guar y goma karaya como agentes estabilizantes sobre algunas características de calidad (bromatológicas, sensoriales y de estabilidad) de helados de crema duros. Métodos: La investigación se desarrolla en dos etapas; en la primera de ellas se evalúa el efecto de las gomas individualmente (100%), en mezclas binarias (50:50 %) y en mezclas ternarias (33.3: 33.3: 33.3 %), aplicadas en un nivel del 0.3% (p/p) en el sistema mezcla de helado duro. En la segunda etapa, se evalúa el efecto del nivel de aplicación en la mezcla de helado duro, ensayando niveles de 0,3, 0,35 y 0,4% (p/p) de la mezcla 50% goma de algarrobo y 50% de goma guar, comparándola contra un testigo que tuvo un estabilizante comercial aplicado al 0,3% (p/p), lo cual originó cuatro tratamientos. Resultados: Con los resultados de la primera fase se realiza la determinación de la tixotropía, lo cual permitió establecer como mejores mezclas las correspondientes a la proporción 50% goma de algarrobo / 50% goma guar y la mezcla 100% de goma guar, de acuerdo con la metodología de superficie de respuesta. La relación final de precios permitió seleccionar la mezcla goma guar: goma de algarrobo para aplicación, sumado a que dicha combinación posibilitó evaluar comportamientos e interacciones como mezcla. En la segunda etapa los resultados arrojan que el helado formado por la mezcla 50% goma de algarrobo y 50% goma guar, presenta un menor porcentaje de derretimiento y un menor tiempo en la caída de la primera gota frente al testigo.

Polymorphisms in the sequences of Marteilia internal transcribed spacer region of the ribosomal RNA genes (ITS-1) in Spain: genetic types are not related with bivalve hosts.

Marteilia refringens is a protozoan parasite causing a disease notifiable to the Office International des Epizooties (OIE) and its distribution has implications for the transfer of live animals. The internal transcribed spacer-1 (ITS-1) from Marteilia clones contains polymorphism. Digestion with HhaI reveals two different restriction profiles, previously referred as 'O' (Marteilia from oyster or Marteilia refringens) and 'M' (Marteilia from mussels or Marteilia maurini). The aim of the present work was to determine whether the two previously described Marteilia molecular types (O and M) exist in the Iberian Peninsula and the strictness of the association with their bivalve host species. The sequence variability in the ITS-1 of Marteilia species was studied in mussels, Mytilus galloprovincialis, and flat oysters, Ostrea edulis, from different geographical locations in Spain, to establish the existence and the distribution of different species or molecular types. Although there were two distinct evolutionary lineages that corresponded more or less strictly with the 'M' and 'O' types, it was evident from the estimated phylogeny that some 'O' types have switched to 'M' type, and vice versa. Moreover, 'O' types were found in mussels and 'M' types were found in oysters, which suggests that there have been several cross-species transmissions of Marteilia between mussels and oysters.

RDP2: recombination detection and analysis from sequence alignments.

UNLABELLED: RDP2 is a Windows 95/XP program that examines nucleotide sequence alignments and attempts to identify recombinant sequences and recombination breakpoints using 10 published recombination detection methods, including GENECONV, BOOTSCAN, MAXIMUM chi(2), CHIMAERA and SISTER SCANNING. The program enables fast automated analysis of large alignments (up to 300 sequences containing 13 000 sites), and interactive exploration, management and verification of results with different recombination detection and tree drawing methods. AVAILABILITY: RDP2 is available free from the RDP2 website (http://darwin.uvigo.es/rdp/rdp.html) CONTACT: darren@science.uct.ac.za SUPPLEMENTARY INFORMATION: Detailed descriptions of RDP2 and the methods it implements are included in the program manual, which can be downloaded from the RDP2 website.

Widespread recombination in published animal mtDNA sequences.

Mitochondrial DNA (mtDNA) recombination has been observed in several animal species, but there are doubts as to whether it is common or only occurs under special circumstances. Animal mtDNA sequences retrieved from public databases were unambiguously aligned and rigorously tested for evidence of recombination. At least 30 recombination events were detected among 186 alignments examined. Recombinant sequences were found in invertebrates and vertebrates, including primates. It appears that mtDNA recombination may occur regularly in the animal cell but rarely produces new haplotypes because of homoplasmy. Common animal mtDNA recombination would necessitate a reexamination of phylogenetic and biohistorical inference based on the assumption of clonal mtDNA transmission. Recombination may also have an important role in producing and purging mtDNA mutations and thus in mtDNA-based diseases and senescence.

The effect of branch length variation on the selection of models of molecular evolution.

Models of sequence evolution play an important role in molecular evolutionary studies. The use of inappropriate models of evolution may bias the results of the analysis and lead to erroneous conclusions. Several procedures for selecting the best-fit model of evolution for the data at hand have been proposed, like the likelihood ratio test (LRT) and the Akaike (AIC) and Bayesian (BIC) information criteria. The relative performance of these model-selecting algorithms has not yet been studied under a range of different model trees. In this study, the influence of branch length variation upon model selection is characterized. This is done by simulating sequence alignments under a known model of nucleotide substitution, and recording how often this true model is recovered by different model-fitting strategies. Results of this study agree with previous simulations and suggest that model selection is reasonably accurate. However, different model selection methods showed distinct levels of accuracy. Some LRT approaches showed better performance than the AIC or BIC information criteria. Within the LRTs, model selection is affected by the complexity of the initial model selected for the comparisons, and only slightly by the order in which different parameters are added to the model. A specific hierarchy of LRTs, which starts from a simple model of evolution, performed overall better than other possible LRT hierarchies, or than the AIC or BIC.

Selecting the best-fit model of nucleotide substitution.

Despite the relevant role of models of nucleotide substitution in phylogenetics, choosing among different models remains a problem. Several statistical methods for selecting the model that best fits the data at hand have been proposed, but their absolute and relative performance has not yet been characterized. In this study, we compare under various conditions the performance of different hierarchical and dynamic likelihood ratio tests, and of Akaike and Bayesian information methods, for selecting best-fit models of nucleotide substitution. We specifically examine the role of the topology used to estimate the likelihood of the different models and the importance of the order in which hypotheses are tested. We do this by simulating DNA sequences under a known model of nucleotide substitution and recording how often this true model is recovered by the different methods. Our results suggest that model selection is reasonably accurate and indicate that some likelihood ratio test methods perform overall better than the Akaike or Bayesian information criteria. The tree used to estimate the likelihood scores does not influence model selection unless it is a randomly chosen tree. The order in which hypotheses are tested, and the complexity of the initial model in the sequence of tests, influence model selection in some cases. Model fitting in phylogenetics has been suggested for many years, yet many authors still arbitrarily choose their models, often using the default models implemented in standard computer programs for phylogenetic estimation. We show here that a best-fit model can be readily identified. Consequently, given the relevance of models, model fitting should be routine in any phylogenetic analysis that uses models of evolution.

Selecting models of nucleotide substitution: an application to human immunodeficiency virus 1 (HIV-1).

The blind use of models of nucleotide substitution in evolutionary analyses is a common practice in the viral community. Typically, a simple model of evolution like the Kimura two-parameter model is used for estimating genetic distances and phylogenies, either because other authors have used it or because it is the default in various phylogenetic packages. Using two statistical approaches to model fitting, hierarchical likelihood ratio tests and the Akaike information criterion, we show that different viral data sets are better explained by different models of evolution. We demonstrate our results with the analysis of HIV-1 sequences from a hierarchy of samples; sequences within individuals, individuals within subtypes, and subtypes within groups. We also examine results for three different gene regions: gag, pol, and env. The Kimura two-parameter model was not selected as the best-fit model for any of these data sets, despite its widespread use in phylogenetic analyses of HIV-1 sequences. Furthermore, the model complexity increased with increasing sequence divergence. Finally, the molecular-clock hypothesis was rejected in most of the data sets analyzed, throwing into question clock-based estimates of divergence times for HIV-1. The importance of models in evolutionary analyses and their repercussions on the derived conclusions are discussed.

Evaluation of methods for detecting recombination from DNA sequences: computer simulations.

Recombination is a key evolutionary process that shapes the architecture of genomes and the genetic structure of populations. Although many statistical methods are available for the detection of recombination from DNA sequences, their absolute and relative performance is still unknown. Here we evaluated the performance of 14 different recombination detection algorithms. We used the coalescent with recombination to simulate DNA sequences with different levels of recombination, genetic diversity, and rate variation among sites. Recombination detection methods were applied to these data sets, and whether they detected or not recombination was recorded. Different recombination methods showed distinct performance depending on the amount of recombination, genetic diversity, and rate variation among sites. The model of nucleotide substitution under which the data were generated did not seem to have a significant effect. Most methods increase power with more sequence divergence. In general, recombination detection methods seem to capture the presence of recombination, but they are not very powerful. Methods that use substitution patterns or incompatibility among sites were more powerful than methods based on phylogenetic incongruence. Most methods do not seem to infer more false positives than expected by chance. Especially depending on the amount of diversity in the data, different methods could be used to attain maximum power while minimizing false positives. Results shown here will provide some guidance in the selection of the most appropriate method/s for the analysis of the particular data at hand.

MODELTEST: testing the model of DNA substitution.

SUMMARY: The program MODELTEST uses log likelihood scores to establish the model of DNA evolution that best fits the data. AVAILABILITY: The MODELTEST package, including the source code and some documentation is available at http://bioag.byu. edu/zoology/crandall_lab/modeltest.html.

Intraspecific gene genealogies: trees grafting into networks.

Intraspecific gene evolution cannot always be represented by a bifurcating tree. Rather, population genealogies are often multifurcated, descendant genes coexist with persistent ancestors and recombination events produce reticulate relationships. Whereas traditional phylogenetic methods assume bifurcating trees, several networking approaches have recently been developed to estimate intraspecific genealogies that take into account these population-level phenomena.