A molecular dynamics simulation study of the solvent isotope effect on copper plastocyanin

The effect of heavy water on the structure and dynamics of copper plastocyanin as well as on some aspects of the solvent dynamics at the protein-solvent interfacial region have been investigated by molecular dynamics simulation. The simulated system has been analyzed in terms of the atomic root mean square deviation and fluctuations, intraprotein H-bond pattern, dynamical cross-correlation map and the results have been compared with those previously obtained for plastocyanin in H2O (Ciocchetti et al. Biophys. Chem. 69 (1997), 185-198). The simulated plastocyanin structure in the two solvents, averaging 1 ns, is very similar along the beta-structure regions, while the most significant differences are registered, analogous to the turns and the regions likely involved in the electron transfer pathway. Moreover, plastocyanin in D2O shows an increase in the number of both the intraprotein H-bonds and the residues involved in correlated motions. An analysis of the protein-solvent coupling evidenced that D2O makes the H-bond formation more difficult with the solvent molecules for positively charged and polar residues, while an opposite trend is observed for negatively charged residues. On the other hand, the frequency of exchange of the solvent molecules involved in the protein-solvent H-bond formation is significantly depressed in D2O. The results are discussed also in connection with protein functionality and briefly with some experimental results connected with the thermostability of proteins in D2O.     

A simulation study of the genetic regulatory hierarchy for butterfly eyespot focus determination

The color patterns on the wings of butterflies have been an important model system in evolutionary developmental biology. Two types of models have been used to study these patterns. The first type of model employs computational techniques and generalized mechanisms of pattern formation to make predictions about how color patterns will vary as parameters of the model are changed. These generalized mechanisms include diffusion gradient, reaction-diffusion, lateral inhibition, and threshold responses. The second type of model uses known genetic interactions from Drosophila melanogaster and patterns of candidate gene expression in one of several butterfly species (most often Junonia (Precis) coenia or Bicyclus anynana) to propose specific genetic regulatory hierarchies that appear to be involved in color pattern formation. This study combines these two approaches using computational techniques to test proposed genetic regulatory hierarchies for the determination of butterfly eyespot foci (also known as border ocelli foci). Two computer programs, STELLA 8.1 and Delphi 2.0, were used to simulate the determination of eyespot foci. Both programs revealed weaknesses in a genetic model previously proposed for eyespot focus determination. On the basis of these simulations, we propose two revised models for eyespot focus determination and identify components of the genetic regulatory hierarchy that are particularly sensitive to changes in model parameter values. These components may play a key role in the evolution of butterfly eyespots. Simulations like these may be useful tools for the study of other evolutionary developmental model systems and reveal similar sensitive components of the relevant genetic regulatory hierarchies.     

基于高密度SNP标记估计群体间遗传关联

联合育种的准确性受到群体间遗传关联程度的影响.本研究通过比较基于系谱数据和基因组数据计算的群体遗传关联,探究高密度SNP标记在遗传关联估计中的应用前景.本研究同时使用了模拟数据和真实数据,采用6种不同的遗传关联计算方法,包括PEVD(prediction error variance of differences)、P...     

A simulation study of mutations in the genetic regulatory hierarchy for butterfly eyespot focus determination

The color patterns on the wings of butterflies have been an important model system in evolutionary developmental biology. A recent computational model tested genetic regulatory hierarchies hypothesized to underlie the formation of butterfly eyespot foci [Evans, T.M., Marcus, J.M., 2006. A simulation study of the genetic regulatory hierarchy for butterfly eyespot focus determination. Evol. Dev. 8, 273-283]. The computational model demonstrated that one proposed hierarchy was incapable of reproducing the known patterns of gene expression associated with eyespot focus determination in wild-type butterflies, but that two slightly modified alternative hierarchies were capable of reproducing all of the known gene expressions patterns. Here we extend the computational models previously implemented in Delphi 2.0 to two mutants derived from the squinting bush brown butterfly (Bicyclus anynana). These two mutants, comet and Cyclops, have aberrantly shaped eyespot foci that are produced by different mechanisms. The comet mutation appears to produce a modified interaction between the wing margin and the eyespot focus that results in a series of comet-shaped eyespot foci. The Cyclops mutation causes the failure of wing vein formation between two adjacent wing-cells and the fusion of two adjacent eyespot foci to form a single large elongated focus in their place. The computational approach to modeling pattern formation in these mutants allows us to make predictions about patterns of gene expression, which are largely unstudied in butterfly mutants. It also suggests a critical experiment that will allow us to distinguish between two hypothesized genetic regulatory hierarchies that may underlie all butterfly eyespot foci.     

A genetic study on the Newards of Nepal valley

The intergroup differences between the three groups of Newars of Nepal (Shrestha, Gubhaju and Jyapu) are not significant for any of the morphological and genetical characters studied. In body measurements the Newars on the whole are similar to other Nepali populations and to several populations of the western and northeastern Himalayas. In serological characters the Newars resemble the Nepalis as well as many of the Himalayan and Assam tribal populations. In mid-phalangeal hair, phenyltheourea tasting ability and colour-blindness the Newars are similar to several Cis-Himalayan groups. In dermatoglyphic traits, the Newars are close to some Mongoloid populations of the Far East and several populations with Mongoloid affinities residing in the western Himalayas.     

Spatial genetic patterns generated by two admixing genetic lineages: a simulation study

Two formerly geographically separated lineages of the zebra mussel Dreissena polymorpha had been given the opportunity to mix extensively across the newly built German Main–Danube canal. We had monitored this admixture of mussel lineages and had described spatial patterns in different genetic measures [Müller et al. 2001 (Heredity, 86: 103); 2002 (Proc. R. Soc. Lond., 269: 1139)]. Here, we present an individual-based model to assess the potential of spatial genetic patterns of detecting and quantifying admixture of mussel lineages. Genetic measures studied are (1) allele frequencies, (2) deviations from Hardy–Weinberg expectations of loci (deficit of heterozygotes, HWD) and (3) linkage disequilibria between unlinked loci (LD). For allele frequencies, we observed a cline over the zone of admixture in all simulations of mixing mussel lineages suggesting that these are appropriate for verification of their mixture. The point of the first contact between lineages was always detectable from their intermediate allele frequencies. LD and HWD were only spatially informative for diagnostic loci or loci with very strong differences in allele frequencies of lineages. For such loci, the probability of disequilibria was highest where lineages had met and decreased towards both sources of lineages Main and Danube. The overall probability of detecting any disequilibrium was higher for LD than for HWD and increased with an increasing rate of genetic interchange. Our simulation results are corroborated by our zebra mussel data and studies from literature. They are applicable to any case of two known linearly mixing genetic lineages.     

Quantitative trait prediction based on genetic marker-array data, a simulation study

MOTIVATION: Using simulation studies for quantitative trait loci (QTL), we evaluate the prediction quality of regression models that include as covariates single-nucleotide polymorphism (SNP) genetic markers which did not achieve genome-wide significance in the original genome-wide association study, but were among the SNPs with the smallest P-value for the selected association test. We compare the results of such regression models to the standard approach which is to include only SNPs that achieve genome-wide significance. Using mean square prediction error as the model metric, our simulation results suggest that by using the coefficient of determination (R(2)) value as a guideline to increase or reduce the number of SNPs included in the regression model, we can achieve better prediction quality than the standard approach. However, important parameters such as trait heritability, the approximate number of QTLs, etc. have to be determined from previous studies or have to be estimated accurately.     

苹果属小金海棠的遗传多样性初步研究

用RAPD技术建立了苹果属小金海棠（Malus xiaojinensis）2个自然分布区的3个群体内随机选取的30株树（10株／每群体）及其相应的子代实生苗共6个群体、60个样本植株的分子标记。通过对15个3承机引物产生的81条RAPD这的统计,计算了不同群体RAPD多态性带的数目。用TREECON软件分析了不同群体及所有个体间的遗传关系,并用AMOVA技术分析了物种的遗传变异。结果是15个引物在全部分析个体中产生了58条多态性带,平均每引物3.8条。现有分布3个群体及其相应的子代实生苗群体的平均多态性带的数目都为1.5条左右。其中平均多态性带的数目最低的群体仅有0.7条,最高的群体也只有2.5条。遗传关系分析表明,2个自然分布区的不同群体间存在遗传分化现象。AMOVA分析显示小金海棠的遗传变异有相当一部分来源于群体间。     

Sex chromosome turnovers and genetic drift: a simulation study

The recent advances of new genomic technologies have enabled the identification and characterization of sex chromosomes in an increasing number of nonmodel species, revealing that many plants and animals undergo frequent sex chromosome turnovers. What evolutionary forces drive these turnovers remains poorly understood, but it was recently proposed that drift might play a more important role than generally assumed. We analysed the dynamics of different types of turnovers using individual‐based simulations and show that when mediated by genetic drift, turnovers are usually easier to achieve than substitutions at neutral markers, but that their dynamics and relative likelihoods vary with the type of the resident and emergent sex chromosome system (XY and/or ZW) and the dominance relationships among the sex‐determining factors. Focusing on turnovers driven by epistatically dominant mutations, we find that drift‐mediated turnovers that preserve the heterogamety pattern are 2–4× more likely than those along which the heterogametic sex changes. This ratio nevertheless decreases along with effective population size and can even reverse in case of extreme polygyny. This can be attributed to a ‘drift‐induced’ selective force, known to influence transitions between male and female heterogamety, but which according to our study does not affect turnovers that preserve the heterogametic sex.     

Partition of the genetic trend to validate multiple selection decisions

In this note, a procedure to partition the genetic trend of a selected population is presented. Each part of the genetic gain accounts for the Mendelian sampling terms of different groups of animals, which can be sometimes assigned to different selection policies. The method is based on a simple transformation of the predicted breeding values. The procedure was illustrated with two simulated examples. In the first example, the genetic trend is partitioned into two pieces, one coming from the selection on sires and the other coming from the selection on dams. The second example shows how the impact of an artificial insemination center in the genetic gain of the whole population can be evaluated.     

植被过滤带对悬浮固体净化效果的模拟

数学模型是进行植被过滤带(VFS)设计的重要工具.本研究通过分析植被过滤带对径流中悬浮固体的净化机理,采用植被过滤带田间尺度机理模型VFSMOD和修正的土壤侵蚀模型MUSLE耦合,对植被过滤带的悬浮固体净化效果进行模拟,并利用野外小区试验数据对该耦合模型进行了验证.结果表明,植被过滤带出流悬浮固体浓度模拟值与实测值的偏差多在±20％以内,其模拟值与实测值的判定系数R2为0.98,该模型具有较高的精度,且优于VFSMOD模型,可用于我国植被过滤带的规划设计.     

The effect of isolated valgus moments on ACL strain during single-leg landing: A simulation study

Valgus moments on the knee joint during single-leg landing have been suggested as a risk factor for anterior cruciate ligament (ACL) injury. The purpose of this study was to test the influence of isolated valgus moment on ACL strain during single-leg landing. Physiologic levels of valgus moments from an in vivo study of single-leg landing were applied to a three-dimensional dynamic knee model, previously developed and tested for ACL strain measurement during simulated landing. The ACL strain, knee valgus angle, tibial rotation, and medial collateral ligament (MCL) strain were calculated and analyzed. The study shows that the peak ACL strain increased nonlinearly with increasing peak valgus moment. Subjects with naturally high valgus moments showed greater sensitivity for increased ACL strain with increased valgus moment, but ACL strain plateaus below reported ACL failure levels when the applied isolated valgus moment rises above the maximum values observed during normal cutting activities. In addition, the tibia was observed to rotate externally as the peak valgus moment increased due to bony and soft-tissue constraints. In conclusion, knee valgus moment increases peak ACL strain during single-leg landing. However, valgus moment alone may not be sufficient to induce an isolated ACL tear without concomitant damage to the MCL, because coupled tibial external rotation and increasing strain in the MCL prevent proportional increases in ACL strain at higher levels of valgus moment. Training that reduces the external valgus moment, however, can reduce the ACL strain and thus may help athletes reduce their overall ACL injury risk.     

Effect of migration and environmental heterogeneity on the maintenance of quantitative genetic variation: a simulation study

The paradox of high genetic variation observed in traits under stabilizing selection is a long‐standing problem in evolutionary theory, as mutation rates appear too low to explain observed levels of standing genetic variation under classic models of mutation–selection balance. Spatially or temporally heterogeneous environments can maintain more standing genetic variation within populations than homogeneous environments, but it is unclear whether such conditions can resolve the above discrepancy between theory and observation. Here, we use individual‐based simulations to explore the effect of various types of environmental heterogeneity on the maintenance of genetic variation (V_A) for a quantitative trait under stabilizing selection. We find that V_A is maximized at intermediate migration rates in spatially heterogeneous environments and that the observed patterns are robust to changes in population size. Spatial environmental heterogeneity increased variation by as much as 10‐fold over mutation–selection balance alone, whereas pure temporal environmental heterogeneity increased variance by only 45% at max. Our results show that some combinations of spatial heterogeneity and migration can maintain considerably more variation than mutation–selection balance, potentially reconciling the discrepancy between theoretical predictions and empirical observations. However, given the narrow regions of parameter space required for this effect, this is unlikely to provide a general explanation for the maintenance of variation. Nonetheless, our results suggest that habitat fragmentation may affect the maintenance of V_A and thereby reduce the adaptive capacity of populations.