Synonymous Nucleotide Divergence and Saturation: Effects of Site-Specific Variations in Codon Bias and Mutation Rates

The synonymous divergence between Escherichia coli and Salmonella typhimurium is explained in a model where there is a large variation between mutation rates at different nucleotide sites in the genome. The model is based on the experimental observation that spontaneous mutation rates can vary over several orders of magnitude at different sites in a gene. Such site-specific variation must be taken into account when studying synonymous divergence and will result in an apparent saturation below the level expected from an assumption of uniform rates. Recently, it has been suggested that codon preference in enterobacteria has a very large site-specific variation and that the synonymous divergence between different species, e.g., E. coli and Salmonella, is saturated. In the present communication it is shown that when site-specific variation in mutation rates is introduced, there is no need to invoke assumptions of saturation and a large variability in codon preference. The same rate variation will also bring average mutation rates as estimated from synonymous sequence divergence into numerical agreement with experimental values. Received: 10 July 1998 / Accepted: 20 August 1998     

Compositional Bias May Affect Both DNA-Based and Protein-Based Phylogenetic Reconstructions

It is now well-established that compositional bias in DNA sequences can adversely affect phylogenetic analysis based on those sequences. Phylogenetic analyses based on protein sequences are generally considered to be more reliable than those derived from the corresponding DNA sequences because it is believed that the use of encoded protein sequences circumvents the problems caused by nucleotide compositional biases in the DNA sequences. There exists, however, a correlation between AT/GC bias at the nucleotide level and content of AT- and GC-rich codons and their corresponding amino acids. Consequently, protein sequences can also be affected secondarily by nucleotide compositional bias. Here, we report that DNA bias not only may affect phylogenetic analysis based on DNA sequences, but also drives a protein bias which may affect analyses based on protein sequences. We present a striking example where common phylogenetic tools fail to recover the correct tree from complete animal mitochondrial protein-coding sequences. The data set is very extensive, containing several thousand sites per sequence, and the incorrect phylogenetic trees are statistically very well supported. Additionally, neither the use of the LogDet/paralinear transform nor removal of positions in the protein alignment with AT- or GC-rich codons allowed recovery of the correct tree. Two taxa with a large compositional bias continually group together in these analyses, despite a lack of close biological relatedness. We conclude that even protein-based phylogenetic trees may be misleading, and we advise caution in phylogenetic reconstruction using protein sequences, especially those that are compositionally biased. Received: 19 February 1998 / Accepted: 28 August 1998     

Testing for age-at-onset anticipation with affected parent-child pairs

The tendency for the onset of a genetic disease to occur at progressively earlier ages or with progressively greater severity in successive generations is known as anticipation. Following the discovery of trinucleotide repeat expansion as a plausible genetic mechanism for anticipation, interest in testing for anticipation has increased. Studies of anticipation can be biased when parents with late onset or children with early onset are preferentially ascertained. This paper presents a nonparametric approach to testing for age-at-onset anticipation that adjusts for such preferential ascertainment. The approach is illustrated through application to data on panic disorder.     

Deletion bias in avian introns over evolutionary timescales

The role that introns play in the function and evolution of nuclear genomes is not fully understood. Recent models of intron evolution suggest that selection and drift may interact to maintain introns in multicellular organisms. In addition, deletion mutations are more likely to become fixed than insertion mutations. Examination of indel substitutions over macroevolutionary timescales in pigeons and doves (Aves: Columbiformes) reveals that deletion substitutions outnumber insertion substitutions by over six times. The length of indel events is variable.     

Evolutionary pressures on apicoplast transit peptides

Malaria parasites (species of the genus Plasmodium) harbor a relict chloroplast (the apicoplast) that is the target of novel antimalarials. Numerous nuclear-encoded proteins are translocated into the apicoplast courtesy of a bipartite N-terminal extension. The first component of the bipartite leader resembles a standard signal peptide present at the N-terminus of secreted proteins that enter the endomembrane system. Analysis of the second portion of the bipartite leaders of P. falciparum, the so-called transit peptide, indicates similarities to plant transit peptides, although the amino acid composition of P. falciparum transit peptides shows a strong bias, which we rationalize by the extraordinarily high AT content of P. falciparum DNA. 786 plastid transit peptides were also examined from several other apicomplexan parasites, as well as from angiosperm plants. In each case, amino acid biases were correlated with nucleotide AT content. A comparison of a spectrum of organisms containing primary and secondary plastids also revealed features unique to secondary plastid transit peptides. These unusual features are explained in the context of secondary plastid trafficking via the endomembrane system.     

A Survey of Codon and Amino Acid Frequency Bias in Microbial Genomes Focusing on Translational Efficiency

Unequal use of synonymous codons has been found in several prokaryotic and eukaryotic genomes. This bias has been associated with translational efficiency. The prevalence of this bias across lineages is currently unknown. Here, a new method (GCB) to measure codon usage bias is presented. It uses an iterative approach for the determination of codon scores and allows the computation of an index of codon bias suitable for interspecies comparison. A server to calculate GCB-values of individual genes as well as a list of compiled results are available at . The method was applied to complete bacterial genomes. The relation of codon usage bias with amino acid composition and the choice of stop codons were determined and discussed.     

Codon Usage Decreases the Error Minimization Within the Genetic Code

The genetic code is not random but instead is organized in such a way that single nucleotide substitutions are more likely to result in changes between similar amino acids. This fidelity, or error minimization, has been proposed to be an adaptation within the genetic code. Many models have been proposed to measure this adaptation within the genetic code. However, we find that none of these consider codon usage differences between species. Furthermore, use of different indices of amino acid physicochemical characteristics leads to different estimations of this adaptation within the code. In this study, we try to establish a more accurate model to address this problem. In our model, a weighting scheme is established for mistranslation biases of the three different codon positions, transition/transversion biases, and codon usage. Different indices of amino acids physicochemical characteristics are also considered. In contrast to pervious work, our results show that the natural genetic code is not fully optimized for error minimization. The genetic code, therefore, is not the most optimized one for error minimization, but one that balances between flexibility and fidelity for different species.     

Phylogeny and the Evolution of the <Emphasis Type="Italic">Amylase</Emphasis> Multigenes in the <Emphasis Type="Italic">Drosophila montium</Emphasis> Species Subgroup

Abstract To investigate the phylogenetic relationships and molecular evolution of α-amylase (Amy) genes in the Drosophila montium species subgroup, we constructed the phylogenetic tree of the Amy genes from 40 species from the montium subgroup. On our tree the sequences of the auraria, kikkawai, and jambulina complexes formed distinct tight clusters. However, there were a few inconsistencies between the clustering pattern of the sequences and taxonomic classification in the kikkawai and jambulina complexes. Sequences of species from other complexes (bocqueti, bakoue, nikananu, and serrata) often did not cluster with their respective taxonomic groups. This suggests that relationships among the Amy genes may be different from those among species due to their particular evolution. Alternatively, the current taxonomy of the investigated species is unreliable. Two types of divergent paralogous Amy genes, the so-called Amy1- and Amy3-type genes, previously identified in the D. kikkawai complex, were common in the montium subgroup, suggesting that the duplication event from which these genes originate is as ancient as the subgroup or it could even predate its differentiation. Thc Amy1-type genes were closer to the Amy genes of D. melanogaster and D. pseudoobscura than to the Amy3-type genes. In the Amy1-type genes, the loss of the ancestral intron occurred independently in the auraria complex and in several Afrotropical species. The GC content at synonymous third codon positions (GC3s) of the Amy1-type genes was higher than that of the Amy3-type genes. Furthermore, the Amy1-type genes had more biased codon usage than the Amy3-type genes. The correlations between GC3s and GC content in the introns (GCi) differed between these two Amy-type genes. These findings suggest that the evolutionary forces that have affected silent sites of the two Amy-type genes in the montium species subgroup may differ.     

Power-law versus exponential distributions of animal group sizes

There has been some confusion concerning the animal group size: an exponential distribution was deduced by maximizing the entropy; lognormal distributions were practically used; as power-law decay with exponent 3/2 was proposed in physical analogy to aerosol condensation. Here I show that the animal group-size distribution follows a power-law decay with exponent 1, and is truncated at a cut-off size which is the expected size of the groups an arbitrary individual engages in. An elementary model of animal aggregation based on binary splitting and coalescing on contingent encounter is presented. The model predicted size distribution holds for various data from pelagic fishes and mammalian herbivores in the wild.