mbs: modifying Hudson's ms software to generate samples of DNA sequences with a biallelic site under selection

<p>Abstract</p> <p>Background</p> <p>The pattern of single nucleotide polymorphisms, or SNPs, contains a tremendous amount of information with respect to the mechanisms of the micro-evolutionary process of a species. The inference of the roles of these mechanisms, including natural selection, relies heavily on computer simulations. A coalescent simulation is extremely powerful in generating a large number of samples of DNA sequences from a population (species) when all mutations are neutral, and Hudson's <b>ms </b>software is frequently used for this purpose.</p> <p>However, it has been difficult to incorporate natural selection into the coalescent framework.</p> <p>Results</p> <p>We herein present a software application to generate samples of DNA sequences when there is a biallelic site targeted by selection. This software application, referred to as <b>mbs</b>, is developed by modifying Hudson's <b>ms</b>. The <b>mbs </b>software is so flexible that it can incorporate any arbitrary histories of population size changes and any mode of selection as long as selection is operating on a biallelic site.</p> <p>Conclusion</p> <p><b>mbs </b>provides opportunities to investigate the effect of any mode of selection on the pattern of SNPs under various demography.</p

The potential role of temperate Japanese regions as refugia for the coral Acropora hyacinthus in the face of climate change

As corals in tropical regions are threatened by increasing water temperatures, poleward range expansion of reef-building corals has been observed, and temperate regions are expected to serve as refugia in the face of climate change. To elucidate the important indicators of the sustainability of coral populations, we examined the genetic diversity and connectivity of the common reef-building coral Acropora hyacinthus along the Kuroshio Current, including recently expanded (<50 years) populations. Among the three cryptic lineages found, only one was distributed in temperate regions, which could indicate the presence of Kuroshio-associated larval dispersal barriers between temperate and subtropical regions, as shown by oceanographic simulations as well as differences in environmental factors. The level of genetic diversity gradually decreased towards the edge of the species distribution. This study provides an example of the reduced genetic diversity in recently expanded marginal populations, thus indicating the possible vulnerability of these populations to environmental changes. This finding underpins the importance of assessing the genetic diversity of newly colonized populations associated with climate change for conservation purposes. In addition, this study highlights the importance of pre-existing temperate regions as coral refugia, which has been rather underappreciated in local coastal management

Potential of Genome-Wide Studies in Unrelated Plus Trees of a Coniferous Species, Cryptomeria japonica (Japanese Cedar)

A genome-wide association study (GWAS) was conducted on more than 30,000 single nucleotide polymorphisms (SNPs) in unrelated first-generation plus tree genotypes from three populations of Japanese cedar Cryptomeria japonica D. Don with genomic prediction for traits of growth, wood properties and male fecundity. Among the assessed populations, genetic characteristics including the extent of linkage disequilibrium (LD) and genetic structure differed and these differences are considered to be due to differences in genetic background. Through population-independent GWAS, several significant SNPs found close to the regions associated with each of these traits and shared in common across the populations were identified. The accuracies of genomic predictions were dependent on the traits and populations and reflected the genetic architecture of traits and genetic characteristics. Prediction accuracies using SNPs selected based on GWAS results were similar to those using all SNPs for several combinations of traits and populations. We discussed the application of genome-wide studies for C. japonica improvement

Directional Positive Selection on an Allele of Arbitrary Dominance

Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive

Letter

dat

How reliable are empirical genomic scans for selective sweeps?

The beneficial substitution of an allele shapes patterns of genetic variation at linked sites. Thus, in principle, adaptations can be mapped by looking for the signature of directional selection in polymorphism data. In practice, such efforts are hampered by the need for an accurate characterization of the demographic history of the species and of the effects of positive selection. In an attempt to circumvent these difficulties, researchers are increasingly taking a purely empirical approach, in which a large number of genomic regions are ordered by summaries of the polymorphism data, and loci with extreme values are considered to be likely targets of positive selection. We evaluated the reliability of the “empirical” approach, focusing on applications to human data and to maize. To do so, we considered a coalescent model of directional selection in a sensible demographic setting, allowing for selection on standing variation as well as on a new mutation. Our simulations suggest that while empirical approaches will identify several interesting candidates, they will also miss many—in some cases, most—loci of interest. The extent of the trade-off depends on the mode of positive selection and the demographic history of the population. Specifically, the false-discovery rate is higher when directional selection involves a recessive rather than a co-dominant allele, when it acts on a previously neutral rather than a new allele, and when the population has experienced a population bottleneck rather than maintained a constant size. One implication of these results is that, insofar as attributes of the beneficial mutation (e.g., the dominance coefficient) affect the power to detect targets of selection, genomic scans will yield an unrepresentative subset of loci that contribute to adaptations

The Coalescent with Selection on Copy Number Variants

We develop a coalescent-based simulation tool to generate patterns of single nucleotide polymorphisms (SNPs) in a wide region encompassing both the original and duplicated genes. Selection on the new duplicated copy and interlocus gene conversion between the two copies are incorporated. This simulation enables us to explore how selection on duplicated copies affects the pattern of SNPs. The fixation of an advantageous duplicated copy causes a strong reduction in polymorphism not only in the duplicated copy but also in its flanking regions, which is a typical signature of a selective sweep by positive selection. After fixation, polymorphism gradually increases by accumulating neutral mutations and eventually reaches the equilibrium value if there is no gene conversion. When gene conversion is active, the number of SNPs in the duplicated copy quickly increases by transferring SNPs from the original copy; therefore, the time when we can recognize the signature of selection is decreased. Because this effect of gene conversion is restricted only to the duplicated region, more power to detect selection is expected if a flanking region to the duplicated copy is used

The effect of gene conversion on the divergence between duplicated genes

Nonindependent evolution of duplicated genes is called concerted evolution. In this article, we study the evolutionary process of duplicated regions that involves concerted evolution. The model incorporates mutation and gene conversion: the former increases d, the divergence between two duplicated regions, while the latter decreases d. It is demonstrated that the process consists of three phases. Phase I is the time until d reaches its equilibrium value, d0. In phase II d fluctuates around d0, and d increases again in phase III. Our simulation results demonstrate that the length of concerted evolution (i.e., phase II) is highly variable, while the lengths of the other two phases are relatively constant. It is also demonstrated that the length of phase II approximately follows an exponential distribution with mean τ, which is a function of many parameters including gene conversion rate and the length of gene conversion tract. On the basis of these findings, we obtain the probability distribution of the level of divergence between a pair of duplicated regions as a function of time, mutation rate, and τ. Finally, we discuss potential problems in genomic data analysis of duplicated genes when it is based on the molecular clock but concerted evolution is common

Neofunctionalization of duplicated genes under the pressure of gene conversion

Neofunctionalization occurs when a neofunctionalized allele is fixed in one of duplicated genes. This is a simple fixation process if duplicated genes accumulate mutations independently. However, the process is very complicated when duplicated genes undergo concerted evolution by gene conversion. Our simulations demonstrate that the process could be described with three distinct stages. First, a newly arisen neofunctionalized allele increases in frequency by selection, but gene conversion prevents its complete fixation. These two factors (selection and gene conversion) that work in opposite directions create an equilibrium, and the time during which the frequency of the neofunctionalized allele drifts around the equilibrium value is called the temporal equilibrium stage. During this temporal equilibrium stage, it is possible that gene conversion is inactivated by mutations, which allow the complete fixation of the neofunctionalized allele. And then, permanent neofunctionalization is achieved. This article develops basic population genetics theories on the process to permanent neofunctionalization under the pressure of gene conversion. We obtain the probability and time that the frequency of a newly arisen neofunctionalized allele reaches the equilibrium value. It is also found that during the temporal equilibrium stage, selection exhibits strong signature in the divergence in the DNA sequences between the duplicated genes. The spatial distribution of the divergence likely has a peak around the site targeted by selection. We provide an analytical expression of the pattern of divergence and apply it to the human red- and green-opsin genes. The theoretical prediction well fits the data when we assume that selection is operating for the two amino acid differences in exon 5, which are believed to account for the major part of the functional difference between the red and green opsins