Substantial regional variation in substitution rates in the human genome: importance of GC content, gene density and telomere-specific effects

This study presents the first global, 1 Mbp level analysis of patterns of nucleotide substitutions along the human lineage. The study is based on the analysis of a large amount of repetitive elements deposited into the human genome since the mammalian radiation, yielding a number of results that would have been difficult to obtain using the more conventional comparative method of analysis. This analysis revealed substantial and consistent variability of rates of substitution, with the variability ranging up to 2-fold among different regions. The rates of substitutions of C or G nucleotides with A or T nucleotides vary much more sharply than the reverse rates suggesting that much of that variation is due to differences in mutation rates rather than in the probabilities of fixation of C/G vs. A/T nucleotides across the genome. For all types of substitution we observe substantially more hotspots than coldspots, with hotspots showing substantial clustering over tens of Mbp's. Our analysis revealed that GC-content of surrounding sequences is the best predictor of the rates of substitution. The pattern of substitution appears very different near telomeres compared to the rest of the genome and cannot be explained by the genome-wide correlations of the substitution rates with GC content or exon density. The telomere pattern of substitution is consistent with natural selection or biased gene conversion acting to increase the GC-content of the sequences that are within 10-15 Mbp away from the telomere.Comment: 35 pages, 6 figure

The dynamics of alternative pathways to compensatory substitution

The role of epistatic interactions among loci is a central question in evolutionary biology and is increasingly relevant in the genomic age. While the population genetics of compensatory substitution have received considerable attention, most studies have focused on the case when natural selection is very strong against deleterious intermediates. In the biologically-plausible scenario of weak to moderate selection there exist two alternate pathways for compensatory substitution. In one pathway, a deleterious mutation becomes fixed prior to occurrence of the compensatory mutation. In the other, the two loci are simultaneously polymorphic. The rates of compensatory substitution along these two pathways and their relative probabilities are functions of the population size, selection strength, mutation rate, and recombination rate. In this paper these rates and path probabilities are derived analytically and verified using population genetic simulations. The expected time durations of these two paths are similar when selection is moderate, but not when selection is weak. The effect of recombination on the dynamics of the substitution process are explored using simulation. Using the derived rates, a phylogenetic substitution model of the compensatory evolution process is presented that could be used for inference of population genetic parameters from interspecific data.Comment: 17 pages, 9 figures, 1 table. Accepted to RECOMB Comparative Genomics Meeting 2013, to be published in BMC Bioinformatic

Currency Preferences in a Tri-Polar Model of Foreign Exchange

This paper reopens the subject of currency preferences while modeling the exchange rates among three major currencies - the US dollar, the euro and the Japanese yen. The exchange rate model presented in this paper includes not only traditional determinants of bilateral exchange rates but incorporates third-currency effects in addition. The obtained estimation results are interpreted from the perspective of possible currency substitution and complementarity relationships. We find evidence of currency complementarity between the yen and the euro, and currency substitution of the dollar for both the euro and the yen. The estimated third-currency effects are consistent with our findings on currency substitution and complementarity among the three major currencies.Exchange Rate Modeling; Currency Substitution; Currency Complementarity; Third-Currency Effects

Genes Translocated into the Plastid Inverted Repeat Show Decelerated Substitution Rates and Elevated GC Content.

Plant chloroplast genomes (plastomes) are characterized by an inverted repeat (IR) region and two larger single copy (SC) regions. Patterns of molecular evolution in the IR and SC regions differ, most notably by a reduced rate of nucleotide substitution in the IR compared to the SC region. In addition, the organization and structure of plastomes is fluid, and rearrangements through time have repeatedly shuffled genes into and out of the IR, providing recurrent natural experiments on how chloroplast genome structure can impact rates and patterns of molecular evolution. Here we examine four loci (psbA, ycf2, rps7, and rps12 exon 2-3) that were translocated from the SC into the IR during fern evolution. We use a model-based method, within a phylogenetic context, to test for substitution rate shifts. All four loci show a significant, 2- to 3-fold deceleration in their substitution rate following translocation into the IR, a phenomenon not observed in any other, nontranslocated plastid genes. Also, we show that after translocation, the GC content of the third codon position and of the noncoding regions is significantly increased, implying that gene conversion within the IR is GC-biased. Taken together, our results suggest that the IR region not only reduces substitution rates, but also impacts nucleotide composition. This finding highlights a potential vulnerability of correlating substitution rate heterogeneity with organismal life history traits without knowledge of the underlying genome structure

Synteny analysis in Rosids with a walnut physical map reveals slow genome evolution in long-lived woody perennials.

BackgroundMutations often accompany DNA replication. Since there may be fewer cell cycles per year in the germlines of long-lived than short-lived angiosperms, the genomes of long-lived angiosperms may be diverging more slowly than those of short-lived angiosperms. Here we test this hypothesis.ResultsWe first constructed a genetic map for walnut, a woody perennial. All linkage groups were short, and recombination rates were greatly reduced in the centromeric regions. We then used the genetic map to construct a walnut bacterial artificial chromosome (BAC) clone-based physical map, which contained 15,203 exonic BAC-end sequences, and quantified with it synteny between the walnut genome and genomes of three long-lived woody perennials, Vitis vinifera, Populus trichocarpa, and Malus domestica, and three short-lived herbs, Cucumis sativus, Medicago truncatula, and Fragaria vesca. Each measure of synteny we used showed that the genomes of woody perennials were less diverged from the walnut genome than those of herbs. We also estimated the nucleotide substitution rate at silent codon positions in the walnut lineage. It was one-fifth and one-sixth of published nucleotide substitution rates in the Medicago and Arabidopsis lineages, respectively. We uncovered a whole-genome duplication in the walnut lineage, dated it to the neighborhood of the Cretaceous-Tertiary boundary, and allocated the 16 walnut chromosomes into eight homoeologous pairs. We pointed out that during polyploidy-dysploidy cycles, the dominant tendency is to reduce the chromosome number.ConclusionSlow rates of nucleotide substitution are accompanied by slow rates of synteny erosion during genome divergence in woody perennials

Currency Substitution, Seigniorage, and Currency Crises in Interdependent Economies

This paper applies a two-country framework that allows for currency substitution in an environment in which policymakers optimally vary interest rates in light of utility-based objectives, one country pegs the value of its currency to the other nation’s currency, and government revenue is generated via explicit taxes and seigniorage. The analysis illustrates the roles that currency substitution, currency preferences, and efficiency of tax systems play in contributing to the likelihood of a “run” on one nation’s currency. We explore how these factors interact to influence the probability of a currency crisis in the country that fixes its exchange rate

An Estimate of the Elasticity of Intertemporal Substitution in a Production Economy

The elasticity of intertemporal substitution (EIS) at the macro level has been estimated mostly based on endowment economy models and these estimates are very sensitive to the choice of interest rates that are used for estimation. Estimates based on production economy models do not need information on interest rates but require endogenous growth models that are free from both scale effects and the strong influence of population growth. Such a model is constructed and EIS is estimated without information on interest rates. The result indicates that EIS at the macro level is as low as 0.09.The elasticity of intertemporal substitution; The degree of relative risk aversion; Production economy; Endogenous growth model

Evolutionary rates and gene dispensability associate with replication timing in the Archaeon Sulfolobus islandicus

In bacterial chromosomes, the position of a gene relative to the single origin of replication generally reflects its replication timing, how often it is expressed, and consequently, its rate of evolution. However, because some archaeal genomes contain multiple origins of replication, bias in gene dosage caused by delayed replication should be minimized and hence the substitution rate of genes should associate less with chromosome position. To test this hypothesis, six archaeal genomes from the genus Sulfolobus containing three origins of replication were selected, conserved orthologs were identified, and the evolutionary rates (dN and dS) of these orthologs were quantified. Ortholog families were grouped by their consensus position and designated by their proximity to one of the three origins (O1, O2, O3). Conserved orthologs were concentrated near the origins and most variation in genome content occurred distant from the origins. Linear regressions of both synonymous and nonsynonymous substitution rates on distance from replication origins were significantly positive, the rates being greatest in the region furthest from any of the origins and slowest among genes near the origins. Genes near O1 also evolved faster than those near O2 and O3, which suggest that this origin may fire later in the cell cycle. Increased evolutionary rates and gene dispensability are strongly associated with reduced gene expression caused in part by reduced gene dosage during the cell cycle. Therefore, in this genus of Archaea as well as in many Bacteria, evolutionary rates and variation in genome content associate with replication timing

Endogenous income taxes and indeterminacy in dynamic models: When Diamond meets Ramsey again.

This paper introduces fiscal increasing returns, through endogenous labor income tax rates as in Schmitt-Grohe and Uribe (1997), into the overlapping generations model with endogenous labor, consumption in both periods of life and homothetic preferences (e.g., Lloyd-Braga, Nourry and Venditti, 2007). We show that under numerical calibrations of the parameters, local indeterminacy can occur for distortionary tax rates that are empirically plausible for the U.S. economy, provided that the elasticity of capital-labor substitution and the wage elasticity of the labor supply are large enough, and the elasticity of intertemporal substitution in consumption is slightly greater than unity. These indeterminacy conditions are similar to those obtained within infinite horizon models and from this point of view, Diamond meets Ramsey again.Indeterminacy; Endogenous labor income tax rate.