Peter D Keightley

..The mechanism supported by our results offers a robust and broadly applicable explanation for the evolutionary advantage of recombination and can explain the spread of costly sex...

..Most deleterious mutations therefore occur in non-coding DNA, and these may make an important contribution to a wide variety of evolutionary processes...

..Unraveling the functional significance of non-coding DNA depends on how well we are able to align non-coding DNA sequences. However, the alignment of non-coding DNA sequences is more difficult than aligning protein-coding sequences...

..91 per diploid genome, per generation. This estimated rate is over twice as large as a previous estimate in murids...

..2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction...

..This result suggests that there is widespread adaptation in mammalian conserved noncoding DNA elements, some of which have been implicated in the regulation of crucially important processes, including development...

..Including coding and noncoding sites, we estimate that the genomic deleterious mutation rate U = 4.2. The mutational load predicted under a multiplicative model is therefore about 99% in hominids...

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..Phenotypic assays of the same lines detected only a small proportion of mutations that were predicted to have evolutionarily significant fitness effects...

..However, the strength of selection on a modifier is less than the summed strengths had there been deleterious mutations only and advantageous mutations only...

..Finally, we show that GC content for each site within INE-1 sequences has evolved toward an equilibrium value (approximately 33%) since insertion...

..This raises questions about the biological mechanism(s) that produce new mutations and has implications for the study of male-driven evolution...

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..Strand-asymmetric mutation bias, coupled with selection to maintain specific nonsynonymous bases, therefore provides an explanation for the extreme base composition of the mitochondrial genome of Drosophila...

..Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans...

..Synonymous site selective constraint is weakest in murids, a surprising result, considering that murid effective population sizes are likely to be considerably higher than the other two taxa...

..Finally, we examine models involving slightly advantageous mutations. We show that the distribution of the absolute strength of selection is well estimated if mutations are assumed to be unconditionally deleterious...

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..Under the variable effects model, we infer that 11% of synonymous mutations are subject to strong purifying selection...

..Furthermore, these findings show that small changes in gene expression can have substantial phenotypic effects...

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..4-cM region, approximately the region from D1Mit451 to D1Mit219. The central QTL also affected tail length and body mass at 3 and 6 weeks of age, but to a lesser degree than 10-week tail length...

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..We show that there is excellent agreement between true and estimated alignments over a wide range of sequence divergences, and that the method outperforms other available alignment methods...

..This bias may be substantial if branch lengths are less than 10N (e) generations...

..melanogaster are positively selected, with a scaled selection coefficient representing the product of the effective population size, N(e), and the strength of selection on heterozygous carriers of ∼2.5...

..Identifying genes that influence phenotypic variation is extremely difficult, especially when the allelic variants only have a small effect. A recent study has used a novel approach to identify a gene that affects the behaviour of mice...

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..If functional, it could mark a turning point in the way we think about the evolution of the genome...

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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...

..Of seven short indel mutations confirmed, six were deletions, consistent with the deletion bias that is thought to exist in Drosophila...

..g., when arrayed along one dimension), although this effect is often modest, especially if some long-distance dispersal is present...

..The frequency of insertion-deletion (indel) errors in non-coding DNA approaches that of single nucleotide errors in non-coding DNA, whereas indel errors are uncommon in coding sequences...

..Nonetheless, given that we expect there to be many mutations induced per line, our results support the hypothesis that mutations vary widely in their effects...

..We evaluate this in the light of data from other MA experiments, along with molecular evidence, that suggest the vast majority of new mutations are deleterious...

..However, there is still a need to collect more data from natural populations and experimental studies, which can be used to test different hypotheses...

..No significant effect was found on the number of bones in the tail or on the dimensions of the ulna, skull, or first vertebra...

..A new study has revealed unexpectedly low numbers of segregating lethal alleles in two species of fish. More experiments are needed, however, to know whether this result is general...

..Deleterious mutations in noncoding DNA have predominantly quantitative effects and could be an important source of the burden of complex genetic disease variation in human populations...

..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...

..Although it likely that this procedure is biased, it is generally assumed that the bias is negligible if species are very closely related...

..Here, we investigate selective constraints in a recent segmental duplication that includes 605 paralogous intron pairs that occurred about 7 million years ago in rice (O. sativa)...

..These may prove to underlie differences in the ecology and behaviour of these diverse species...

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..On a cancer-susceptible Apc(Min/+) background, Mbd4-/- mice showed accelerated tumor formation with CpG --> TpG mutations in the Apc gene. Thus MBD4 suppresses CpG mutability and tumorigenesis in vivo...

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