Mutation accumulation in <Emphasis Type="Italic">Tetrahymena</Emphasis>

Background  

The rate and fitness effects of mutations are key in understanding the evolution of every species. Traditionally, these parameters are estimated in mutation accumulation experiments where replicate lines are propagated in conditions that allow mutations to randomly accumulate without the purging effect of natural selection. These experiments have been performed with many model organisms but we still lack empirical estimates of the rate and effects of mutation in the protists.     

The relationship between the error catastrophe, survival of the flattest, and natural selection

Background  

The quasispecies model is a general model of evolution that is generally applicable to replication up to high mutation rates. It predicts that at a sufficiently high mutation rate, quasispecies with higher mutational robustness can displace quasispecies with higher replicative capacity, a phenomenon called "survival of the flattest". In some fitness landscapes it also predicts the existence of a maximum mutation rate, called the error threshold, beyond which the quasispecies enters into error catastrophe, losing its genetic information. The aim of this paper is to study the relationship between survival of the flattest and the transition to error catastrophe, as well as the connection between these concepts and natural selection.     

Codon usage in twelve species of <Emphasis Type="Italic">Drosophila</Emphasis>

Background  

Codon usage bias (CUB), the uneven use of synonymous codons, is a ubiquitous observation in virtually all organisms examined. The pattern of codon usage is generally similar among closely related species, but differs significantly among distantly related organisms, e.g., bacteria, yeast, and Drosophila. Several explanations for CUB have been offered and some have been supported by observations and experiments, although a thorough understanding of the evolutionary forces (random drift, mutation bias, and selection) and their relative importance remains to be determined. The recently available complete genome DNA sequences of twelve phylogenetically defined species of Drosophila offer a hitherto unprecedented opportunity to examine these problems. We report here the patterns of codon usage in the twelve species and offer insights on possible evolutionary forces involved.     

Barriers to antigenic escape by pathogens: trade-off between reproductive rate and antigenic mutability

Background  

A single measles vaccination provides lifelong protection. No antigenic variants that escape immunity have been observed. By contrast, influenza continually evolves new antigenic variants, and the vaccine has to be updated frequently with new strains. Both measles and influenza are RNA viruses with high mutation rates, so the mutation rate alone cannot explain the differences in antigenic variability.     

Viruses and thyroiditis: an update

Background

Despite the demonstration that geminiviruses, like many other single stranded DNA viruses, are evolving at rates similar to those of RNA viruses, a recent study has suggested that grass-infecting species in the genus Mastrevirus may have co-diverged with their hosts over millions of years. This "co-divergence hypothesis" requires that long-term mastrevirus substitution rates be at least 100,000-fold lower than their basal mutation rates and 10,000-fold lower than their observable short-term substitution rates. The credibility of this hypothesis, therefore, hinges on the testable claim that negative selection during mastrevirus evolution is so potent that it effectively purges 99.999% of all mutations that occur.

Results

We have conducted long-term evolution experiments lasting between 6 and 32 years, where we have determined substitution rates of between 2 and 3 × 10^-4 substitutions/site/year for the mastreviruses Maize streak virus (MSV) and Sugarcane streak Réunion virus (SSRV). We further show that mutation biases are similar for different geminivirus genera, suggesting that mutational processes that drive high basal mutation rates are conserved across the family. Rather than displaying signs of extremely severe negative selection as implied by the co-divergence hypothesis, our evolution experiments indicate that MSV and SSRV are predominantly evolving under neutral genetic drift.

Conclusion

The absence of strong negative selection signals within our evolution experiments and the uniformly high geminivirus substitution rates that we and others have reported suggest that mastreviruses cannot have co-diverged with their hosts.     

Measuring the prevalence of regional mutation rates: an analysis of silent substitutions in mammals,fungi, and insects

Background  

The patterns of mutation vary both within and across genomes. It has been shown for a few mammals that mutation rates vary within the genome, while for unknown reasons, the sensu stricto yeasts have uniform rates instead. The generality of these observations has been unknown. Here we examine silent site substitutions in a more expansive set (20 mammals, 27 fungi, 4 insects) to determine why some genomes demonstrate this mosaic distribution and why others are uniform.     

Development and experimental verification of a genome-scale metabolic model for Corynebacterium glutamicum

Background  

In silico genome-scale metabolic models enable the analysis of the characteristics of metabolic systems of organisms. In this study, we reconstructed a genome-scale metabolic model of Corynebacterium glutamicum on the basis of genome sequence annotation and physiological data. The metabolic characteristics were analyzed using flux balance analysis (FBA), and the results of FBA were validated using data from culture experiments performed at different oxygen uptake rates.     

GeneBins: a database for classifying gene expression data,with application to plant genome arrays

Background  

To interpret microarray experiments, several ontological analysis tools have been developed. However, current tools are limited to specific organisms.     

Codon usage is associated with the evolutionary age of genes in metazoan genomes

Background  

Codon usage may vary significantly between different organisms and between genes within the same organism. Several evolutionary processes have been postulated to be the predominant determinants of codon usage: selection, mutation, and genetic drift. However, the relative contribution of each of these factors in different species remains debatable. The availability of complete genomes for tens of multicellular organisms provides an opportunity to inspect the relationship between codon usage and the evolutionary age of genes.     

A genome-wide view of mutation rate co-variation using multivariate analyses

Background  

While the abundance of available sequenced genomes has led to many studies of regional heterogeneity in mutation rates, the co-variation among rates of different mutation types remains largely unexplored, hindering a deeper understanding of mutagenesis and genome dynamics. Here, utilizing primate and rodent genomic alignments, we apply two multivariate analysis techniques (principal components and canonical correlations) to investigate the structure of rate co-variation for four mutation types and simultaneously explore the associations with multiple genomic features at different genomic scales and phylogenetic distances.     

Large scale comparison of global gene expression patterns in human and mouse

Background  

It is widely accepted that orthologous genes between species are conserved at the sequence level and perform similar functions in different organisms. However, the level of conservation of gene expression patterns of the orthologous genes in different species has been unclear. To address the issue, we compared gene expression of orthologous genes based on 2,557 human and 1,267 mouse samples with high quality gene expression data, selected from experiments stored in the public microarray repository ArrayExpress.     

Stone age diseases and modern AIDS

Background

Recent reports have indicated that single-stranded DNA (ssDNA) viruses in the taxonomic families Geminiviridae, Parvoviridae and Anellovirus may be evolving at rates of ~10^-4 substitutions per site per year (subs/site/year). These evolution rates are similar to those of RNA viruses and are surprisingly high given that ssDNA virus replication involves host DNA polymerases with fidelities approximately 10 000 times greater than those of error-prone viral RNA polymerases. Although high ssDNA virus evolution rates were first suggested in evolution experiments involving the geminivirus maize streak virus (MSV), the evolution rate of this virus has never been accurately measured. Also, questions regarding both the mechanistic basis and adaptive value of high geminivirus mutation rates remain unanswered.

Results

We determined the short-term evolution rate of MSV using full genome analysis of virus populations initiated from cloned genomes. Three wild type viruses and three defective artificial chimaeric viruses were maintained in planta for up to five years and displayed evolution rates of between 7.4 × 10^-4 and 7.9 × 10^-4 subs/site/year.

Conclusion

These MSV evolution rates are within the ranges observed for other ssDNA viruses and RNA viruses. Although no obvious evidence of positive selection was detected, the uneven distribution of mutations within the defective virus genomes suggests that some of the changes may have been adaptive. We also observed inter-strand nucleotide substitution imbalances that are consistent with a recent proposal that high mutation rates in geminiviruses (and possibly ssDNA viruses in general) may be due to mutagenic processes acting specifically on ssDNA molecules.     

Expression breadth and expression abundance behave differently in correlations with evolutionary rates

Background  

One of the main objectives of the molecular evolution and evolutionary systems biology field is to reveal the underlying principles that dictate protein evolutionary rates. Several studies argue that expression abundance is the most critical component in determining the rate of evolution, especially in unicellular organisms. However, the expression breadth also needs to be considered for multicellular organisms.     

Sexual selection does not influence minisatellite mutation rate

Background  

Moller and Cuervo report a significant trend between minisatellite mutation rate and the frequency of extra-pair copulations in birds. This is interpreted as evidence that the high rate of evolution demanded by sexual selection has itself selected for a higher mutation rate in species where selection is strongest. However, there are good a priori reasons for believing that their method of calculating minisatellite mutation rates will be highly error prone and a poor surrogate measure of the evolutionary rate of genes. I therefore attempted to replicate their results using both their data and an independent data set based on papers they failed to locate.     

A survey of motif discovery methods in an integrated framework

Background  

There has been a growing interest in computational discovery of regulatory elements, and a multitude of motif discovery methods have been proposed. Computational motif discovery has been used with some success in simple organisms like yeast. However, as we move to higher organisms with more complex genomes, more sensitive methods are needed. Several recent methods try to integrate additional sources of information, including microarray experiments (gene expression and ChlP-chip). There is also a growing awareness that regulatory elements work in combination, and that this combinatorial behavior must be modeled for successful motif discovery. However, the multitude of methods and approaches makes it difficult to get a good understanding of the current status of the field.     

Novel genes exhibit distinct patterns of function acquisition and network integration

Background  

Genes are created by a variety of evolutionary processes, some of which generate duplicate copies of an entire gene, while others rearrange pre-existing genetic elements or co-opt previously non-coding sequence to create genes with 'novel' sequences. These novel genes are thought to contribute to distinct phenotypes that distinguish organisms. The creation, evolution, and function of duplicated genes are well-studied; however, the genesis and early evolution of novel genes are not well-characterized. We developed a computational approach to investigate these issues by integrating genome-wide comparative phylogenetic analysis with functional and interaction data derived from small-scale and high-throughput experiments.     

The effects of low-impact mutations in digital organisms

Background  

Avida is a computer program that performs evolution experiments with digital organisms. Previous work has used the program to study the evolutionary origin of complex features, namely logic operations, but has consistently used extremely large mutational fitness effects. The present study uses Avida to better understand the role of low-impact mutations in evolution.     

Extraction of phylogenetic network modules from the metabolic network

Background  

In bio-systems, genes, proteins and compounds are related to each other, thus forming complex networks. Although each organism has its individual network, some organisms contain common sub-networks based on function. Given a certain sub-network, the distribution of organisms common to it represents the diversity of its function.     

Sample size for detecting differentially expressed genes in microarray experiments

Background  

Microarray experiments are often performed with a small number of biological replicates, resulting in low statistical power for detecting differentially expressed genes and concomitant high false positive rates. While increasing sample size can increase statistical power and decrease error rates, with too many samples, valuable resources are not used efficiently. The issue of how many replicates are required in a typical experimental system needs to be addressed. Of particular interest is the difference in required sample sizes for similar experiments in inbred vs. outbred populations (e.g. mouse and rat vs. human).