Adam Eyre-Walker

..Caution must therefore be excercised in the use of parsimony...

..This problem is exacerbated by the removal of low-frequency polymorphisms. However, selection on synonymous codon use restricts the conditions under which artifactual evidence of adaptive evolution is produced...

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..Only approximately 10% or fewer of mutations seem to behave as SDMs, but SDMs could comprise a substantial fraction of mutations in protein-coding genes that have a chance of becoming fixed between species...

..Estimates in microorganisms are even higher. By contrast, there is little evidence of widespread adaptive evolution in our own species...

..g., coding or regulatory) depends largely upon the mean strength of selection; this has implications for understanding which types of mutations are likely to be responsible for the variance in fitness and inherited disease...

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..However, although we have known about isochores for over 25 years, we still have a poor understanding of why they exist. In this article, we review the current evidence for the three main hypotheses...

..However, the population-genetic evidence, although not conclusive, is strongly suggestive of recombination in mitochondrial DNA. The implications of non-clonality for our understanding of human and mitochondrial evolution are discussed...

..The results therefore suggest that selection may be acting upon the base composition of isochores and large sections of junk DNA...

..We present evidence which suggests that hypervariable sites do not exist in our data. It therefore seems likely that recombination has occurred between mitochondrial lineages in humans...

..For others, it cannot be determined whether the recombinants are real or produced by laboratory error. Either way, the results have important implications for how mtDNA is sequenced and used...

..These results are of interest because they confirm the recently suggested disappearance of GC-rich isochores in some mammalian genomes, and more importantly, they suggest that this disappearance started very early in mammalian evolution...

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..However, coding sequence detection methods are biased against detecting such very short open reading frames. Thus, a substantial number of non-canonical coding regions encoding short peptides might await characterization...

..Approximately half of these seem to be generated simultaneously since they have identical minor allele frequencies. We estimate that the mutation of adjacent nucleotides accounts for a little less than 1% of all SNPs...

..Furthermore, we identify regions that contain high numbers of coincident SNPs and suggest that one in particular, a region containing the gene PRIM2, may be under balancing selection...

..The analysis of several Drosophila data sets suggests that approximately 25% +/- 20% of amino acid substitutions were driven by positive selection in the divergence between D. simulans and D. yakuba...

..We find no evidence in support of the hypothesis that this variation could be due to different metabolic rates...

..The low rate of adaptive evolution and the high proportion of effectively neutral substitution in species with small N(e) are expected to combine to make it difficult to detect adaptive molecular evolution in species with small N(e)...

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..We conclude that there is substantial variation in the mutation that has, until now, been hidden from view...

..Our analysis also suggests that the level of adaptive evolution has probably been underestimated, possibly substantially, in both bacteria and Drosophila...

..This provides an alternative neutral explanation for the accumulation of TEs in upstream sequences...

..coli and S. enterica lineages. We also show that the proportion of adaptive substitutions is uncorrelated with the rate of amino acid substitution or gene function but that it may be correlated with levels of synonymous codon usage bias...

..We also demonstrate how the same framework can be used to estimate the proportion of adaptive gene expression evolution...

..Finally, we show that the density of mutations varies at a 10-Mb and a chromosomal scale, but that the variation at these scales is weak...

..We show that the predicted pattern of evolution is observed...

..yakuba. We estimate that 45% of all amino-acid substitutions have been fixed by natural selection, and that on average one adaptive substitution occurs every 45 years in these species...

..We show by simulation that even very low levels of SDM, relative to the rate of point mutation, can generate a substantial excess of inverted repeats...

..We propose that the differential distribution of Alu elements is likely to be due to a change in their pattern of insertion or their probability of fixation through evolutionary time...

..Genuine adjacent substitutions may be due to mutation or selection...

..Under the relative fitness model, we show that depends jointly on U and the selective effects of new deleterious mutations and that a species could tolerate 10's or even 100's of new deleterious mutations per genome each generation...

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..We observe very similar results in all species; we find little evidence of adaptive amino acid substitution in any comparison except sunflowers. This may be because many plant species have modest effective population sizes...

..Variation in the mutation rate has important implications in evolutionary biology and underexplored implications for our understanding of hereditary disease and cancer...

..We conclude that sequence directed mutagenesis is not prevalent in eukaryotes and that the examples of human diseases, apparently caused by sequence directed mutagenesis, are probably coincidental...

..However, we find no correlation between either the mean GC3 or the standard deviation in GC3 and body temperature...

..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...

..We also show that the Euclidean distance yields low estimates of expression divergence for genes with a conserved uniform pattern of expression...

..However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs...

..Our results provide an estimate of the distribution of fitness effects of weakly selected mutations and provide a possible explanation for why the molecular clock is fairly constant across taxa and time...

..We therefore suggest that a new statistic be used to study patterns of selection when data are sparse, the direction of selection: DoS = D(n)/(D(n) + D(s)) - P(n)/(P(n) + P(s))...

..However, the patterns of compositional change suggested by the polymorphism and divergence data differ, suggesting the possibility of two murid shifts...

..The variance in the ratio of amino acid and synonymous substitution rates is dominated by gene effects, but there is also a significant gene-by-lineage interaction...

..The results suggest that mutation biases are not solely responsible for the compositional biases found in noncoding regions...

..We also investigated other factors affecting the mode of evolution in the disease genes: Ka/Ks is significantly affected by protein function, mode of inheritance, and the reduction of life expectancy caused by disease...

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..In this article we review the existing support for these two hypotheses, and discuss how they can be combined to provide a new perspective on isochore evolution...

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..This has resulted in the accumulation of a large number of deleterious mutations in sequences containing gene control elements and hence a widespread degradation of the genome during the evolution of humans and chimpanzees...

..melanogaster. D. melanogaster therefore seems to have evolved in its courtship behaviors by the recruitment of a new chimeric gene...

..Considering each amino acid by itself confirms our results. We conclude that selection on synonymous codon use in E. coli is largely due to selection for translational accuracy, to reduce the costs of both missense and nonsense errors...