Identifying and removing fast-evolving sites using compatibility analysis: an example from the Arthropoda.
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Animals↗
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Results for “Models of evolution”
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Using novel phylogenetic methods to evaluate mammalian mtDNA, including amino acid-invariant sites-LogDet plus site stripping, to detect internal conflicts in the data, with special reference to the positions of hedgehog, armadillo, and elephant.
We look at the higher-order phylogeny of mammals, analyzing in detail the complete mtDNA sequences of more than 40 species. We test the support for several proposed superordinal relationships. To this end, we apply a number of recently programmed methods and approaches, plus better-established methods. New pairwise tests show highly significant evidence that amino acid frequencies are changing among nearly all the genomes studied when unvaried sites are ignored. LogDet amino acid distances, with modifications to take into account invariant sites, are combined with bootstrapping and the Neighbor Joining algorithm to account for these violations of standard models. To weight the more slowly evolving sites, we exclude the more rapidly evolving sites from the data by using "site stripping". This leads to changing optimal trees with nearly all methods. The bootstrap support for many hypotheses varies widely between methods, and few hypotheses can claim unanimous support from these data. Rather, we uncover good evidence that many of the earlier branching patterns in the placental subtree could be incorrect, including the placement of the root. The tRNA genes, for example, favor a split between the group hedgehog, rodents, and primates versus all other sequenced placentals. Such a grouping is not ruled out by the amino acid sequence data. A grouping of all rodents plus rabbit, the old Glires hypothesis, is also feasible with stripped amino acid data, and rodent monophyly is also common. The elephant sequence allows confident rejection of the older taxon Ferungulata (Simpson, 1945). In its place, the new taxa Scrotifera and Fereuungulata are defined. A new likelihood ratio test is used to detect differences between the optimal tree for tRNA versus that for amino acids. While not clearly significant as made, some results indicate the test is tending towards significance with more general models of evolution. Individual placement tests suggest alternative positions for hedgehog and elephant. Congruence arguments to support elephant and armadillo together are striking, suggesting a superordinal group composed of Xenarthra and African endemic mammals, which in turn may be near the root of the placental subtree. Thus, while casting doubt on some recent conclusions, the analyses are also unveiling some interesting new possibilities.
Animals↗
Phase space evolution distribution functions for high energy electron beams.
The phase space evolution (PSE) model is a 3D electron beam dose calculation model for radiation oncology. The PSE model is based upon the transport of electrons with a specific energy and direction over short distances (typically 0.3-1 cm). The result of the transport of these electrons is described by an energy and direction distribution of the electrons, which is stored in a database. The database is used by the PSE model at the time of the actual electron transport simulation. A good agreement between dose distributions calculated by the PSE model and EGS4 Monte Carlo code for mono-energetic, mono-directional electron beams was found. The differences in point dose are within 1-2% of the maximum dose. These differences can be caused by errors in the database used, or by assumptions made in the PSE model. The aim of this paper is to get more insight into the possible errors introduced by the database. Results show that the data in the database are in good agreement with EGS4 calculated data. Also the influence of the database on a PSE calculated dose distribution has been investigated. The differences between a PSE calculated dose distribution and an EGS4 calculated dose distribution can be reduced to < 0.5% if the database is replaced by a database partly created by EGS4. This shows that small errors in the database have a distinct effect on the dose distribution, and that this dose distribution can be calculated accurately by the PSE model if the right database is used.
Computer Simulation↗
Nuclear medicine dosimetry.
A brief overview is provided of the history of the development of internal dose methods for use in nuclear medicine. Basic methods of internal dosimetry and the systems that have been developed for use in nuclear medicine are described. The development of the MIRD system and the International Radiopharmaceutical Dosimetry Symposium series is outlined. The evolution of models and tools for calculating dose estimates is reviewed. Current efforts in developing more patient-specific methods, particularly for use in therapy calculations, development of small scale and microdosimetry techniques, and of relating internal radiation doses to observed biological effects are described and evaluated.
Algorithms↗
Comparison of additive trees using circular orders.
It has been postulated that existing species have been linked in the past in a way that can be described using an additive tree structure. Any such tree structure reflecting species relationships is associated with a matrix of distances between the species considered which is called a distance matrix or a tree metric matrix. A circular order of elements of X corresponds to a circular (clockwise) scanning of the subset X of vertices of a tree drawn on a plane. This paper describes an optimal algorithm using circular orders to compare the topology of two trees given by their distance matrices. This algorithm allows us to compute the Robinson and Foulds topologic distance between two trees. It employs circular order tree reconstruction to compute an ordered bipartition table of the tree edges for both given distance matrices. These bipartition tables are then compared to determine the Robinson and Foulds topologic distance, known to be an important criterion of tree similarity. The described algorithm has optimal time complexity, requiring O(n(2)) time when performed on two n x n distance matrices. It can be generalized to get another optimal algorithm, which enables the strict consensus tree of k unrooted trees, given their distance matrices, to be constructed in O(kn(2)) time.
Algorithms↗
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.
Algorithms↗
PAQ: Partition Analysis of Quasispecies.
MOTIVATION: The complexities of genetic data may not be accurately described by any single analytical tool. Phylogenetic analysis is often used to study the genetic relationship among different sequences. Evolutionary models and assumptions are invoked to reconstruct trees that describe the phylogenetic relationship among sequences. Genetic databases are rapidly accumulating large amounts of sequences. Newly acquired sequences, which have not yet been characterized, may require preliminary genetic exploration in order to build models describing the evolutionary relationship among sequences. There are clustering techniques that rely less on models of evolution, and thus may provide nice exploratory tools for identifying genetic similarities. Some of the more commonly used clustering methods perform better when data can be grouped into mutually exclusive groups. Genetic data from viral quasispecies, which consist of closely related variants that differ by small changes, however, may best be partitioned by overlapping groups. RESULTS: We have developed an intuitive exploratory program, Partition Analysis of Quasispecies (PAQ), which utilizes a non-hierarchical technique to partition sequences that are genetically similar. PAQ was used to analyze a data set of human immunodeficiency virus type 1 (HIV-1) envelope sequences isolated from different regions of the brain and another data set consisting of the equine infectious anemia virus (EIAV) regulatory gene rev. Analysis of the HIV-1 data set by PAQ was consistent with phylogenetic analysis of the same data, and the EIAV rev variants were partitioned into two overlapping groups. PAQ provides an additional tool which can be used to glean information from genetic data and can be used in conjunction with other tools to study genetic similarities and genetic evolution of viral quasispecies.
Algorithms↗
Evolution of selective neutrality: further considerations.
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Animals↗
More on the overdispersed molecular clock.
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Alleles↗
Measures of synteny conservation between species pairs.
Measures of conserved synteny are important for estimating the relative rates of chromosomal evolution in various lineages. We present a natural way to view the synteny conservation between two species from an Oxford grid--an r x c table summarizing the number of orthologous genes on each of the chromosomes 1 through r of the first species that are on each of the chromosomes 1 through c of the second species. This viewpoint suggests a natural statistic, which we denote by rho and call syntenic correlation, designed to measure the amount of synteny conservation between two species. This measure allows syntenic conservation to be compared across many pairs of species. We improve the previous methods for estimating the true number of conserved syntenies given the observed number of conserved syntenies by taking into account the dependency of the numbers of orthologues observed in the chromosome pairings between the two species and by determining both point and interval estimators. We also discuss the application of our methods to genomes that contain chromosomes of highly variable lengths and to estimators of the true number of conserved segments between species pairs.
Biological Evolution↗
The problem of counting sites in the estimation of the synonymous and nonsynonymous substitution rates: implications for the correlation between the synonymous substitution rate and codon usage bias.
Most methods for estimating the rate of synonymous and nonsynonymous substitution per site define a site as a mutational opportunity: the proportion of sites that are synonymous is equal to the proportion of mutations that would be synonymous under the model of evolution being considered. Here we demonstrate that this definition of a site can give misleading results and that a physical definition of site should be used in some circumstances. We illustrate our point by reexamining the relationship between codon usage bias and the synonymous substitution rate. It has recently been shown that the rate of synonymous substitution, calculated using the Goldman-Yang method, which encapsulates the mutational-opportunity definition of a site at a high level of sophistication, is either positively correlated or uncorrelated to synonymous codon bias in Drosophila. Using other methods, which account for synonymous codon bias but define a site physically, we show that there is a negative correlation between the synonymous substitution rate and codon bias and that the lack of a negative correlation using the Goldman-Yang method is due to the way in which the number of synonymous sites is counted. We also show that there is a positive correlation between the synonymous substitution rate and third position GC content in mammals, but that the relationship is considerably weaker than that obtained using the Goldman-Yang method. We argue that the Goldman-Yang method is misleading in this context and conclude that methods that rely on a mutational-opportunity definition of a site should be used with caution.
Animals↗
Recombination modification in a flucturating environment.
This paper examines the theory of the evolution of increased recombination between two loci subjected to interactive selection in a temporally fluctuating environment. Both cyclical and stochastic environments are considered. It is shown that temporal variation in the linkage disequilibrium coefficient for the pair of selected loci, due to fluctuations in the selective values of the genotypes at these loci, can give rise to selection in favor of modifier genes increasing recombination. The equilibrium level of recombination established in a given population depends on several factors; it is highest for intermediate values of the environmental periodicity or autocorrelation, for cases when the modifier genes are themselves linked to the selected loci, and for high levels of environmental variation. In general, it seems that the rate of modification of recombination values by this process will be low except when the modifiers are tightly linked to the selected loci. The possible evolutionary significance of this process is discussed in relation to observations on genetic systems of plants and animals.
Biological Evolution↗
Dietary restriction and aging: comparative tests of evolutionary hypotheses.
Dietary restriction (DR) increases life span in many types of animals. The response to chronic DR may be an adaptation to environments with variable food levels. This study uses the comparative method to test evolutionary predictions about the origin of the response to DR, using data from 10 species of rotifers. Most species, but not all, responded to DR by increasing mean life span, maximum life span, reproductive life span, mortality rate doubling time, and initial mortality rate. Interspecific comparisons did not show the predicted correlations between the strength of the response to DR and either reproductive life span, age of first reproduction, or total reproduction. There was support for the idea that the response to chronic DR is associated with changes in reproductive allocation during short-term periods of starvation: species that reduced reproduction when starved increased their life spans under DR, whereas species that continued to reproduce when starved decreased their life spans under DR.
Aging↗
Salivary progesterone levels and rate of ovulation are significantly lower in poorer than in better-off urban-dwelling Bolivian women.
BACKGROUND: Agriculturalists in less-developed countries (LDC) have lower progesterone levels than urban industrialized populations. However, it is unknown if urban LDC populations are also relatively lower. We tested whether urban Bolivia samples-poorer (Bol-p) and better-off (Bol-b)-have lower progesterone than a Chicago (USA) sample, and whether progesterone and rate of ovulation are lower in Bol-p than in Bol-b. METHODS: Serial salivary samples collected from Bolivians, screened according to strict exclusion criteria during two complete menstrual cycles, were radioimmunoassayed for progesterone; anthropometrics were collected at mid-follicular and mid-luteal phases. RESULTS: Progesterone levels are lower in the Bolivia samples, and higher in the Bol-b than Bol-p; ovulation rate is greater in Bol-b than Bol-p. For only ovulatory cycles, mean-follicular-P (pmol/l), mean-luteal-P (pmol/l), and mean-peak-P (pmol/l) are respectively 65, 142 and 208 in Bol-p; 76, 167 and 232 in Bol-b; and 96, 240 and 330 in Chicago. Principal components representing body-size and progesterone level are positively correlated (r = 0.404, P = 0.005). CONCLUSIONS: Progesterone levels appear to be influenced by chronic and acute ecological conditions, evidenced by the association with body-size and the probability of ovulation respectively. These findings have implications for understanding cancer aetiology, developing population-appropriate hormonal contraceptives, and modelling the evolution and functioning of the reproductive system.
Adult↗
Cross-talk between RNA and prions.
As concepts evolve in mammalian and yeast prion biology, rather preliminary research investigating the interplay between prion and RNA processes are gaining momentum. The yeast prion [PSI+] represents an aggregated state of the translation termination factor Sup35 resulting in the tendency of ribosomes to readthrough stop codons. This "nonsense suppression" activity is investigated for its possible physiological role to engender on Saccharomyces cerevisiae the ability to respond to stress or variable growth conditions and thereby act as a capacitor to evolve. The interaction between prion and RNA is a two way street--the cell may have adopted RNA processes in translation to govern the presence of prions and the [PSI+] prion's nonsense suppressor phenotype may exhibit different growth phenotypes by its control of translation termination. RNA processes in the mammalian cell also effect and are affected by prions.
Animals↗
Early life origins of insulin resistance and type 2 diabetes in India and other Asian countries.
There is a rapidly increasing epidemic of type 2 diabetes in India and other Asian countries. The thrifty genotype and the thrifty phenotype are two nonexclusive explanations. People in the Indian subcontinent have faced undernutrition for many generations, and Indian babies are among the smallest in the world. However, the diabetes epidemic is of recent origin, and diabetes is more common among urban than rural Indians despite the higher birth weight of urban babies. This suggests that postnatal factors must also contribute. Thus, a life-course model of evolution of insulin resistance and type 2 diabetes, incorporating fetal, postnatal and adult components, seems most appropriate. For a given BMI, Indians have a higher percentage of body fat and more visceral fat than members of other populations. This thin-fat phenotype is present at birth. Neonatal size and body composition are influenced by parental size, maternal food intake, physical activity and circulating concentrations of nutrients and metabolites (folate, glucose, triglycerides, cholesterol etc.). Maternal insulin resistance promotes transfer of nutrients to the fetus. Accelerated childhood growth is another risk factor for adiposity and insulin resistance, especially in children born small. Childhood growth seems to be more influenced by paternal genetic factors, whereas intrauterine growth is more influenced by maternal factors (intrauterine environment). Urban lifestyles, including poor diet and sedentary habits, promote further obesity, insulin resistance and type 2 diabetes. These factors may be amenable to correction. Prevention of type 2 diabetes must begin in utero and continue throughout the life course.
Adipose Tissue↗
Application of phylogenetic networks in evolutionary studies.
The evolutionary history of a set of taxa is usually represented by a phylogenetic tree, and this model has greatly facilitated the discussion and testing of hypotheses. However, it is well known that more complex evolutionary scenarios are poorly described by such models. Further, even when evolution proceeds in a tree-like manner, analysis of the data may not be best served by using methods that enforce a tree structure but rather by a richer visualization of the data to evaluate its properties, at least as an essential first step. Thus, phylogenetic networks should be employed when reticulate events such as hybridization, horizontal gene transfer, recombination, or gene duplication and loss are believed to be involved, and, even in the absence of such events, phylogenetic networks have a useful role to play. This article reviews the terminology used for phylogenetic networks and covers both split networks and reticulate networks, how they are defined, and how they can be interpreted. Additionally, the article outlines the beginnings of a comprehensive statistical framework for applying split network methods. We show how split networks can represent confidence sets of trees and introduce a conservative statistical test for whether the conflicting signal in a network is treelike. Finally, this article describes a new program, SplitsTree4, an interactive and comprehensive tool for inferring different types of phylogenetic networks from sequences, distances, and trees.
Animals↗
Novel ceftazidime-resistance beta-lactamases generated by a codon-based mutagenesis method and selection.
Four known and nine new ceftazidime-resistance beta-lactamases were generated by a novel, contaminating codon-based mutagenesis approach. In this method, wild-type codons are spiked with a set of mutant codons during oligonucleotide synthesis, generating random combinatorial libraries of primers that contain few codon replacements per variant. Mutant codons are assembled by tandem addition of a diluted mixture of five Fmoc-dimer amidites to the growing oligo and a mixture of four DMTr-monomer amidites to generate 20 trinucleotides that encode a set of 18 amino acids. Wild-type codons are assembled with conventional chemistry and the whole process takes place in only one synthesis column, making its automation feasible. The random and binomial behavior of this approach was tested in the polylinker region of plasmid pUC19 by the synthesis of three oligonucleotide libraries mutagenized at different rates and cloned as mutagenic cassettes. Additionally, the method was biologically assessed by mutating six contiguous codons that encode amino acids 237-243 (ABL numbering) of the TEM(pUC19) beta-lactamase, which is functionally equivalent to the clinically important TEM-1 beta-lactamase. The best ceftazidime-recognizing variant was a triple mutant, R164H:E240K: R241A, displaying a 333-fold higher resistance than the wild-type enzyme.
Amino Acid Substitution↗