In my recent Perspectives article, I reviewed what we know about human mutation rates and their effects, and I highlighted the potential long-term consequences of established goals in human medicine ([Lynch 2016][1]). Given the complexity of the personal and societal issues, with conflicting short-
This paper describes software created to search for and analyze pairs of duplicate genes within a genome. The process is based on a program that uses aligned amino acid sequences to generate a corresponding alignment of the underlying nucleotide sequences and perform a codon by codon comparison of the nucleotides. Observed numbers of nucleotide substitutions can be used to make inferences about the ages of gene duplication events and the effects of natural selection acting on duplicate genes.
The evolution of the eukaryotic cell marked a profound moment in Earth’s history, with most of the visible biota coming to rely on intracellular membrane-bound organelles. It has been suggested that this evolutionary transition was critically dependent on the movement of ATP synthesis from the cell surface to mitochondrial membranes and the resultant boost to the energetic capacity of eukaryotic cells. However, contrary to this hypothesis, numerous lines of evidence suggest that eukaryotes are no more bioenergetically efficient than prokaryotes. Thus, although the origin of the mitochondrion was a key event in evolutionary history, there is no reason to think membrane bioenergetics played a direct, causal role in the transition from prokaryotes to eukaryotes and the subsequent explosive diversification of cellular and organismal complexity.
Information on the genetic correlation between traits provides fundamental insight into the constraints on the evolutionary process. Estimates of such correlations are conventionally obtained by raising individuals of known relatedness in artificial environments. However, many species are not readily amenable to controlled breeding programmes, and considerable uncertainty exists over the extent to which estimates derived under benign laboratory conditions reflect the properties of populations in natural settings. Here, non-invasive methods that allow the estimation of genetic correlations from phenotypic measurements derived from individuals of unknown relatedness are introduced. Like the conventional approach, these methods demand large sample sizes in order to yield reasonably precise estimates, and special precautions need to be taken to eliminate bias from shared environmental effects. Provided the sample consists of at least 20% or so relatives, informative estimates of the genetic correlation are obtainable with sample sizes of several hundred individuals, particularly if supplemental information on relatedness is available from polymorphic molecular markers.
All eukaryotes have three essential nuclear multisubunit RNA polymerases, abbreviated as Pol I, Pol II and Pol III. Plants are remarkable in having two additional multisubunit RNA polymerases, Pol IV and Pol V, which synthesize noncoding RNAs that coordinate RNA-directed DNA methylation for silencing of transposons and a subset of genes. Based on their subunit compositions, Pols IV and V clearly evolved as specialized forms of Pol II, but their catalytic properties remain undefined. Here, we show that Pols IV and V differ from one another, and Pol II, in nucleotide incorporation rate, transcriptional accuracy and the ability to discriminate between ribonucleotides and deoxyribonucleotides. Pol IV transcription is considerably more error-prone than Pols II or V, which may be tolerable in its synthesis of short RNAs that serve as precursors for siRNAs targeting non-identical members of transposon families. By contrast, Pol V exhibits high fidelity transcription, similar to Pol II, suggesting a need for Pol V transcripts to faithfully reflect the DNA sequence of target loci to which siRNA-Argonaute silencing complexes are recruited.
Abstract Because spontaneous mutation is the source of all genetic diversity, measuring mutation rates can reveal how natural selection drives patterns of variation within and between species. We sequenced eight genomes produced by a mutation-accumulation experiment in Drosophila melanogaster. Our analysis reveals that point mutation and small indel rates vary significantly between the two different genetic backgrounds examined. We also find evidence that ∼2% of mutational events affect multiple closely spaced nucleotides. Unlike previous similar experiments, we were able to estimate genome-wide rates of large deletions and tandem duplications. These results suggest that, at least in inbred lines like those examined here, mutational pressures may result in net growth rather than contraction of the Drosophila genome. By comparing our mutation rate estimates to polymorphism data, we are able to estimate the fraction of new mutations that are eliminated by purifying selection. These results suggest that ∼99% of duplications and deletions are deleterious—making them 10 times more likely to be removed by selection than nonsynonymous mutations. Our results illuminate not only the rates of new small- and large-scale mutations, but also the selective forces that they encounter once they arise.
Abstract Spontaneous mutations were accumulated in 100 replicate lines of Caenorhabditis elegans over a period of ∼50 generations. Periodic assays of these lines and comparison to a frozen control suggest that the deleterious mutation rate for typical life-history characters in this species is at least 0.05 per diploid genome per generation, with the average mutational effect on the order of 14% or less in the homozygous state and the average mutational heritability ∼0.0034. While the average mutation rate per character and the average mutational heritability for this species are somewhat lower than previous estimates for Drosophila, these differences can be reconciled to a large extent when the biological differences between these species are taken into consideration.
