Pre-rRNA processing and the path from the RNA world.
Explore the source record for details and available documents.
Biological Evolution↗
Biomedical subjects
D Penny
Publications and source records attributed to D Penny.
Use of spectral analysis to test hypotheses on the origin of pinnipeds.
The evolutionary origin of the pinnipeds (seals, sea lions, and walruses) is still uncertain. Most authors support a hypothesis of a monophyletic origin of the pinnipeds from a caniform carnivore. A minority view suggests a diphyletic origin with true seals being related to the mustelids (otters and ferrets). The phylogenetic relationships of the walrus to other pinniped and carnivore families are also still particularly problematic. Here we examined the relative support for mono- and diphyletic hypotheses using DNA sequence data from the mitochondrial small subunit (12S) rRNA and cytochrome b genes. We first analyzed a small group of taxa representing the three pinniped families (Phocidae, Otariidae, and Odobenidae) and caniform carnivore families thought to be related to them. We inferred phylogenetic reconstructions from DNA sequence data using standard parsimony and neighbor-joining algorithms for phylogenetic inference as well as a new method called spectral analysis (Hendy and Penny) in which phylogenetic information is displayed independently of any selected tree. We identified and compensated for potential sources of error known to lead to selection of incorrect phylogenetic trees. These include sampling error, unequal evolutionary rates on lineages, unequal nucleotide composition among lineages, unequal rates of change at different sites, and inappropriate tree selection criteria. To correct for these errors, we performed additional transformations of the observed substitution patterns in the sequence data, applied more stringent structural constraints to the analyses, and included several additional taxa to help resolve long, unbranched lineages in the tree. We find that there is strong support for a monophyletic origin of the pinnipeds from within the caniform carnivores, close to the bear/raccoon/panda radiation. Evidence for a diphyletic origin was very weak and can be partially attributed to unequal nucleotide compositions among the taxa analyzed. Subsequently, there is slightly more evidence for grouping the walrus with the eared seals versus the true seals. A more conservative interpretation, however, is that the walrus is an early, but not the first, independent divergence from the common pinniped ancestor.
Algorithms↗
Improved analyses of human mtDNA sequences support a recent African origin for Homo sapiens.
New quantitative methods are applied to the 135 human mitochondrial sequences from the Vigilant et al. data set. General problems in analyzing large numbers of short sequences are discussed, and an improved strategy is suggested. A key feature is to focus not on individual trees but on the general "landscape" of trees. Over 1,000 searches were made from random starting trees with only one tree (a local optimum) being retained each time, thereby ensuring optima were found independently. A new tree comparison metric was developed that is unaffected by rearrangements of trees around many very short internal edges. Use of this metric showed that downweighting hypervariable sites revealed more evolutionary structure than studies that weighted all sites equally. Our results are consistent with convergence toward a global optimum. Crucial features are that the best optima show very strong regional differentiation, a common group of 49 African sequences is found in all the best optima, and the best optima contain the 16 !Kung sequences in a separate group of San people. The other 86 sequences form a heterogeneous mixture of Africans, Europeans, Australopapuans, and Asians. Thus all major human lineages occur in Africa, but only a subset occurs in the rest of the world. The existence of these African-only groups strongly contradicts multiregional theories for the origin of Homo sapiens that require widespread migration and interbreeding over the entire range of H. erectus. Only when the multiregional model is rejected is it appropriate to consider the root, based on a single locus, to be the center of origin of a population (otherwise different loci could give alternative geographic positions for the root). For this data, several methods locate the root within the group of 49 African sequences and are thus consistent with the recent African origin of H. sapiens. We demonstrate that the time of the last common ancestor cannot be the time of major expansion in human numbers, and our results are thus also consistent with recent models that differentiate between the last common ancestor, expansion out of Africa, and the major expansion in human populations. Such a two-phase model is consistent with a wide range of molecular and archeological evidence.
Africa↗
A discrete Fourier analysis for evolutionary trees.
Discrete Fourier transformations have recently been developed to model the evolution of two-state characters (the Cavender/Farris model). We report here the extension of these transformations to provide invertible relationships between a phylogenetic tree T (with three probability parameters of nucleotide substitution on each edge corresponding to Kimura's 3ST model) and the expected frequencies of the nucleotide patterns in the sequences. We refer to these relationships as spectral analysis. In either model with independent and identically distributed site substitutions, spectral analysis allows a global correction for all multiple substitutions (second- and higher-order interactions), independent of any particular tree. From these corrected data we use a least-squares selection procedure, the closest tree algorithm, to infer an evolutionary tree. Other selection criteria such as parsimony or compatibility analysis could also be used; each of these criteria will be statistically consistent for these models. The closest tree algorithm selects a unique best-fit phylogenetic tree together with independent edge length parameters for each edge. The method is illustrated with an analysis of some primate hemoglobin sequences.
Animals↗
Regional ventricular wall motion abnormalities in tricuspid atresia after the Fontan procedure: flawed methodology may lead to a spurious finding of hypokinesia.
We believe that the two-frame method described by Akagi et al. cannot adequately describe the highly abnormal wall motion characteristics of these post-Fontan ventricles, and the systolic hypokinesia they describe may be spurious. Our data show that the predominant abnormality is incoordinate relaxation of the ventricular wall, which in turn prolongs the time constant of relaxation and the isovolumetric relaxation time and leads to reduced early rapid filling. Indeed, it was these abnormalities of diastolic, not systolic, function that were the strongest predictor of poor exercise performance in our study of patients late after the Fontan procedure. We strongly believe that the analysis of ventricular wall motion requires sequential data throughout the cardiac cycle, with well defined reference points concerning the timing of cardiac events, so that misinterpretation can be avoided.
Heart↗
The effects of sequence length, tree topology, and number of taxa on the performance of phylogenetic methods.
Simulations were used to study the performance of several character-based and distance-based phylogenetic methods in obtaining the correct tree from pseudo-randomly generated input data. The study included all the topologies of unrooted binary trees with from 4 to 10 pendant vertices (taxa) inclusive. The length of the character sequences used ranged from 10 to 10(5) characters exponentially. The methods studied include Closest Tree, Compatibility, Li's method, Maximum Parsimony, Neighbor-joining, Neighborliness, and UPGMA. We also provide a modification to Li's method (SimpLi) which is consistent with additive data. We give estimations of the sequence lengths required for given confidence in the output of these methods under the assumptions of molecular evolution used in this study. A notation for characterizing all tree topologies is described. We show that when the number of taxa, the maximum path length, and the minimum edge length are held constant, there it little but significant dependence of the performance of the methods on the tree topology. We show that those methods that are consistent with the model used perform similarly, whereas the inconsistent methods, UPGMA and Li's method, perform very poorly.
Base Sequence↗
Confidence in evolutionary trees from biological sequence data.
The reliable construction of evolutionary trees from nucleotide sequences often depends on randomization tests such as the bootstrap and PTP (cladistic permutation tail probability) tests. The genomes of bacteria, viruses, animals and plants, however, vary widely in their nucleotide frequencies. Where genomes have independently acquired similar G+C base compositions, signals in the data arise that cause methods of evolutionary tree reconstruction to estimate the wrong tree by grouping together sequences with similar G+C content. Under these conditions randomization tests can lead to both the rejection of the correct evolutionary hypothesis and acceptance of an incorrect hypothesis (such as with the contradictory inferences from the photosynthetic rbcS and rbcL sequences). We have proposed one approach to testing for G+C content problem. Here we present a formalization of this method, a frequency-dependent significance test, which has general application.
Base Sequence↗
Neighbor-joining uses the optimal weight for net divergence.
A class of phylogenetic clustering methods which calculate net divergences from distance data, but assign differing weights to the net divergences, is defined. The class includes the Neighbor-Joining Method and the Unweighted Pair-Group Method with Arithmetic Mean. The accuracy of some of these methods is studied by computer simulation for the case of four taxa under the additive tree hypothesis. Of these methods and under this hypothesis, it is proved that Neighbor-Joining uses the only weighting for net divergence which is consistent, so that it is the only method in the class which is expected to converge to the correct tree as more data are added. Neighbor-Joining is then compared with Closest Tree on Distances for five taxa by simulation. It is proved that Closest Tree on Distances is equivalent to Neighbor-Joining for four taxa, though it is not when more than four taxa are considered.
Cluster Analysis↗
A multidisciplinary investigation of a cluster of deaths on a paediatric intensive care unit.
During late December 1989 and early January 1990, a cluster of six unexplained deaths occurred on a paediatric intensive care unit (PICU) among children with congenital heart disease who had undergone cardiac surgical procedures. The children were all aged three years or less. In each case death was preceded by an unexpected increase in ventilatory pressure requirement followed by the development of a similar pulmonary shadowing on chest radiography. The radiological abnormality was felt to be consistent with a pneumonitis associated with some small airway disease. The clustering of these deaths, occurring in a similar unusual manner, was felt to constitute an outbreak warranting investigation. An Incident Committee was established to plan and manage a large multidisciplinary investigation during which the unit was temporarily closed. Following extensive investigation no bacterium, virus, fungus or other pathogen, toxic agent, or any other explanation for the cluster of deaths could be found. The possibility that the cluster occurred by chance remains although this was felt to be unlikely.
Cause of Death↗
Controversy on chloroplast origins.
Controversy exists over the origins of photosynthetic organelles in that contradictory trees arise from different sequence, biochemical and ultrastructural data sets. We propose a testable hypothesis which explains this inconsistency as a result of the differing GC contents of sequences. We report that current methods of tree reconstruction tend to group sequences with similar GC contents irrespective of whether the similar GC content is due to common ancestry or is independently acquired. Nuclear encoded sequences (high GC) give different trees from chloroplast encoded sequences (low GC). We find that current data is consistent with the hypothesis of multiple origins for photosynthetic organelles and single origins for each type of light harvesting complex.
Base Composition↗
Genetic characterization of pathogenic Leptospira species by DNA hybridization.
A total of 66 serovars of potentially pathogenic Leptospira species were examined by slot blot hybridization, and 57 of these serovars were classified in six DNA homology groups. In cases in which common serovars were studied, the results were in general agreement with the results of previous workers, who used different DNA homology methods. However, we propose a new species, Leptospira kirschneri, comprising the following serovars: bulgarica, butembo, cynopteri, dania, grippotyphosa, kabura, kambale, ramisi, and tsaratsovo. Seven of these serovars have not had their DNAs studied by other workers.
DNA, Bacterial↗
Eukaryote origins. Seeds of a universal tree.
Explore the source record for details and available documents.
Animals↗
Right ventricular diastolic function in children.
Explore the source record for details and available documents.
Child↗
Pulmonary blood flow after total cavopulmonary shunt.
The pattern of pulmonary blood flow was studied in three patients after a total cavopulmonary shunt procedure. Doppler studies showed a phasic pattern of flow which varied with the respiratory cycle. Pulmonary blood flow was increased with normal inspiration, and was much augmented by the Mueller manoeuvre. This suggests that flow was occurring when a negative intrathoracic pressure was generated. During a brief Valsalva manoeuvre blood flowed away from the lungs. With a sustained Valsalva manoeuvre there was no spontaneous forward flow; instead there was low velocity pulsatile pulmonary blood flow that coincided with ventricular systole. Left ventricular cavity dimensions decreased, reflecting a considerably reduced pulmonary blood flow. Pulmonary blood flow after the total cavopulmonary shunt operation is critically dependent on changes in intrathoracic pressure. This has important implications in terms of the immediate postoperative management of these patients.
Adolescent↗
Distribution of the number of matches between nucleotide sequences.
When two strings of symbols are aligned it is important to know whether the observed number of matches is better than that expected between two independent sequences with the same frequency of symbols. When strings are of different lengths, nulls need to be inserted in order to align the sequences. One approach is to use simple approximations of sampling for replacement. We describe an algorithm for exactly determining the frequencies of given numbers of matches, sampling without replacement. This does not lead to a simple closed form expression. However, we show examples where sampling with, or without, replacement give very similar results and the simple approach may be adequate for all but the smallest cases.
Base Sequence↗
Minimally colored trees.
Each edge in a weighted colored tree has a nonnegative weight corresponding to the colors of its incident vertices. The sum of these weights is the weight of the tree. Algorithms of O(n) are known to find minimal colorings, that is, to assign colors from a given finite set to the vertices of a tree so as to minimize the weight of the tree. In this paper generating functions are used to find the number of minimal colorings and the average weight of each edge over such colorings, also using O(n) operations. Applications to evolutionary trees are given.
Algorithms↗
Influenza viruses, comets and the science of evolutionary trees.
The study of phylogeny is becoming increasing scientific in that hypotheses can be tested quantitatively. We report a method of estimating the probabilities of obtaining a tree of a given length from nucleic acid sequence data. The method is applied to the hypothesis of Hoyle & Wickramasinghe that the earth is being continually bombarded by influenza (and other) viruses which originate from comets. A quantitative analysis of sequences from the H1 strain of human influenza viruses contradicts three versions of the Hoyle-Wickramasinghe model. One non-evolutionary version of their model has less than one chance in 10(66) of being correct. A version that allowed extraterrestrial evolution has less than one change in 10(6) of being correct. The sequence data is in agreement with the biological (evolutionary) model. The results are discussed from the aspect of the falsifiability of evolutionary theory.
Base Sequence↗
What, if anything, is Prochloron?
Explore the source record for details and available documents.
Biological Evolution↗