Journal of Molecular Evolution

Unstable DNA Repair Genes Shaped by Their Own Sequence Modifying Phenotypes.

Publication Date: 2010 Mar 6 PMID: 20213140
Authors: Falster, D. S. - Nakken, S. - Bergem-Ohr, M. - Rodland, E. A. - Breivik, J.
Journal: J Mol Evol

The question of whether natural selection favors genetic stability or genetic variability is a fundamental problem in evolutionary biology. Bioinformatic analyses demonstrate that selection favors genetic stability by avoiding unstable nucleotide sequences in protein encoding DNA. Yet, such unstable sequences are maintained in several DNA repair genes, thereby promoting breakdown of repair and destabilizing the genome. Several studies have therefore argued that selection favors genetic variability at the expense of stability. Here we propose a new evolutionary mechanism, with supporting bioinformatic evidence, that resolves this paradox. Combining the concepts of gene-dependent mutation biases and meiotic recombination, we argue that unstable sequences in the DNA mismatch repair (MMR) genes are maintained by their own phenotype. In particular, we predict that human MMR maintains an overrepresentation of mononucleotide repeats (monorepeats) within and around the MMR genes. In support of this hypothesis, we report a 31% excess in monorepeats in 250 kb regions surrounding the seven MMR genes compared to all other RefSeq genes (1.75 vs. 1.34%, P = 0.0047), with a particularly high content in PMS2 (2.41%, P = 0.0047) and MSH6 (2.07%, P = 0.043). Based on a mathematical model of monorepeat frequency, we argue that the proposed mechanism may suffice to explain the observed excess of repeats around MMR genes. Our findings thus indicate that unstable sequences in MMR genes are maintained through evolution by the MMR mechanism. The evolutionary paradox of genetically unstable DNA repair genes may thus be explained by an equilibrium in which the phenotype acts back on its own genotype.

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The Rate of Unequal Crossing Over in the dumpy Gene from Drosophila melanogaster.

Publication Date: 2010 Mar 5 PMID: 20204610
Authors: Carmon, A. - Larson, M. - Wayne, M. - Macintyre, R.
Journal: J Mol Evol

The PIGSFEAST (PF) exon of the Drosophila dumpy gene is undergoing concerted evolution by the process of unequal crossing over. We have developed a long-range PCR-based assay to amplify the approximately 12 kb long exon which contains variable numbers of 303 or 306 nt long repeats in a tandem array. We applied this procedure to mutation accumulation lines of Drosophila melanogaster established by M. Wayne and L. Higgins. Nine new repeat length variants were found in these lines allowing us to measure the rate of unequal crossing over in the PF exon. The rate, which for several reasons is an underestimate, is 7.05 x 10(-4) exchanges per generation.

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Enhancing the Prebiotic Relevance of a Set of Covalently Self-Assembling, Autorecombining RNAs Through In Vitro Selection.

Publication Date: 2010 Mar 3 PMID: 20198367
Authors: Burton, A. S. - Lehman, N.
Journal: J Mol Evol

An in vitro form of the self-splicing group-I intron interrupting the Azoarcus tRNA(Ile) was shortened by ~10% with the removal of helix P6a. This deletion reduced the reverse-splicing activity of the ribozyme about 10-fold. Through in vitro selection, this activity was restored in several low-error mutants. A number of mutations were found that improved reverse-splicing activity through both increased k (obs) and better folding. The deletion mutant could be fragmented into as many as three discrete pieces, which, when incubated together, were capable of covalent self-assembly through energy-neutral transesterification reactions, a process called autorecombination. A subset of the mutations identified through in vitro selection for reverse-splicing were exaptations in that they were also shown to augment the autorecombination reactions, leading to higher yields of covalently self-assembled products, making this the smallest such system yet discovered.

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Evolution of Repeated Sequences in the Ribosomal DNA Intergenic Spacer of 32 Arthropod Species.

Publication Date: 2010 Feb 27 PMID: 20191268
Authors: Ambrose, C. D. - Crease, T. J.
Journal: J Mol Evol

The evolution of a multigene family (MGF) is affected by the structure and function of its regulatory elements, specifically by the link between recombination and DNA transcription and/or replication. The ribosomal DNA (rDNA) MGF is often hierarchically repetitive, combining function with repetition in a single genic system. Its tandemly repeated operons contain the transcription unit of the 45S ribosomal RNA precursor alternating with an intergenic spacer (IGS) that commonly includes repeated transcription regulatory elements. To study the evolution of repeated sequences and the influence of repeat characteristics on their sequence divergence, we sequenced and characterized a single complete IGS from 11 daphniid species and analyzed their repeat arrays along with those from an additional 21 species of arthropods. We tested the hypotheses that sequence similarity is higher among tandemly arrayed repeats than among interleaved or dispersed repeats, and that the homogeneity of repeat arrays is affected by the number and the length of repeats, as well as by the presence of putative regulatory elements. We found that both tandem repeat organization and the presence of a TATA motif are significantly correlated with increased sequence similarity among homologous IGS repeats. We also observed that some repeat types are only found in a single species, while others appear to have persisted for >100 MY, with evidence for homologous repeat types in sister species. Taken together, these data suggest that both drift and natural selection influence repeat evolution within the IGS.

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Stochasticity Versus Determinism: Consequences for Realistic Gene Regulatory Network Modelling and Evolution.

Publication Date: 2010 Feb 12 PMID: 20151115
Authors: Jenkins, D. J. - Stekel, D. J.
Journal: J Mol Evol

Gene regulation is one important mechanism in producing observed phenotypes and heterogeneity. Consequently, the study of gene regulatory network (GRN) architecture, function and evolution now forms a major part of modern biology. However, it is impossible to experimentally observe the evolution of GRNs on the timescales on which living species evolve. In silico evolution provides an approach to studying the long-term evolution of GRNs, but many models have either considered network architecture from non-adaptive evolution, or evolution to non-biological objectives. Here, we address a number of important modelling and biological questions about the evolution of GRNs to the realistic goal of biomass production. Can different commonly used simulation paradigms, in particular deterministic and stochastic Boolean networks, with and without basal gene expression, be used to compare adaptive with non-adaptive evolution of GRNs? Are these paradigms together with this goal sufficient to generate a range of solutions? Will the interaction between a biological goal and evolutionary dynamics produce trade-offs between growth and mutational robustness? We show that stochastic basal gene expression forces shrinkage of genomes due to energetic constraints and is a prerequisite for some solutions. In systems that are able to evolve rates of basal expression, two optima, one with and one without basal expression, are observed. Simulation paradigms without basal expression generate bloated networks with non-functional elements. Further, a range of functional solutions was observed under identical conditions only in stochastic networks. Moreover, there are trade-offs between efficiency and yield, indicating an inherent intertwining of fitness and evolutionary dynamics.

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