Inequality in mutation rates of the two strands of DNA

As the mechanisms for replicating the two strands of duplex DNA differ it is, in principle, possible for the mutation rates to differ depending on which strand is being copied. In the absence of selection this would lead to a difference in the measured rate of a particular base substitution, such as T to C, depending on which DNA strand was analysed to determine the rate. Thus a change such as T to C on one DNA strand results from either a direct T-to-C mutation on that strand or an A-to-G mutation on the complementary strand; for the other strand the situation is reversed, and it can be seen that different processes are responsible for the two cases, allowing for asymmetry in substitution rate. We have tested whether such asymmetry indeed occurs by studying equivalent sequences from the beta-globin complexes of six species of primate. Our results reveal an asymmetry in substitution rates consistent with predictions based on strand-inequalities in mutation rates. Our sequence comparisons also allow us to make predictions about the positions of replication origins and the replication error rates of one strand relative to the other.     

Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila

Spontaneous mutations are the source of genetic variation required for evolutionary change, and are therefore important for many aspects of evolutionary biology. For example, the divergence between taxa at neutrally evolving sites in the genome is proportional to the per nucleotide mutation rate, u (ref. 1), and this can be used to date speciation events by assuming a molecular clock. The overall rate of occurrence of deleterious mutations in the genome each generation (U) appears in theories of nucleotide divergence and polymorphism, the evolution of sex and recombination, and the evolutionary consequences of inbreeding. However, estimates of U based on changes in allozymes or DNA sequences and fitness traits are discordant. Here we directly estimate u in Drosophila melanogaster by scanning 20 million bases of DNA from three sets of mutation accumulation lines by using denaturing high-performance liquid chromatography. From 37 mutation events that we detected, we obtained a mean estimate for u of 8.4 x 10(-9) per generation. Moreover, we detected significant heterogeneity in u among the three mutation-accumulation-line genotypes. By multiplying u by an estimate of the fraction of mutations that are deleterious in natural populations of Drosophila, we estimate that U is 1.2 per diploid genome. This high rate suggests that selection against deleterious mutations may have a key role in explaining patterns of genetic variation in the genome, and help to maintain recombination and sexual reproduction.     

Coevolution with viruses drives the evolution of bacterial mutation rates

Bacteria with greatly elevated mutation rates (mutators) are frequently found in natural and laboratory populations, and are often associated with clinical infections. Although mutators may increase adaptability to novel environmental conditions, they are also prone to the accumulation of deleterious mutations. The long-term maintenance of high bacterial mutation rates is therefore likely to be driven by rapidly changing selection pressures, in addition to the possible slow transition rate by point mutation from mutators to non-mutators. One of the most likely causes of rapidly changing selection pressures is antagonistic coevolution with parasites. Here we show whether coevolution with viral parasites could drive the evolution of bacterial mutation rates in laboratory populations of the bacterium Pseudomonas fluorescens. After fewer than 200 bacterial generations, 25% of the populations coevolving with phages had evolved 10- to 100-fold increases in mutation rates owing to mutations in mismatch-repair genes; no populations evolving in the absence of phages showed any significant change in mutation rate. Furthermore, mutator populations had a higher probability of driving their phage populations extinct, strongly suggesting that mutators have an advantage against phages in the coevolutionary arms race. Given their ubiquity, bacteriophages may play an important role in the evolution of bacterial mutation rates.     

变异率和种群数目自适应的遗传算法

提出了针对个体变异率和种群数目的2种自适应方法.算法中个体变异率根据其适度值在种群中的排序自适应调整,使优良个体具有较小的变异率继续进化,而使种群中较差个体具有较大变异率,增强了种群搜索能力.同时根据种群个体适度值方差动态调整变异率曲线,种群数目调整则根据最优个体更新率动态增大,以动态适应解空间的规模避免采样误差造成的进化停滞.通过在不同尺度的NK Landscape上与传统的简单遗传算法(SGA)比较可得,2种自适应方法的引入对遗传算法的寻优能力有了明显改进.     

Genetic diversity and disease control in rice

Crop heterogeneity is a possible solution to the vulnerability of monocultured crops to disease. Both theory and observation indicate that genetic heterogeneity provides greater disease suppression when used over large areas, though experimental data are lacking. Here we report a unique cooperation among farmers, researchers and extension personnel in Yunnan Province, China--genetically diversified rice crops were planted in all the rice fields in five townships in 1998 and ten townships in 1999. Control plots of monocultured crops allowed us to calculate the effect of diversity on the severity of rice blast, the major disease of rice. Disease-susceptible rice varieties planted in mixtures with resistant varieties had 89% greater yield and blast was 94% less severe than when they were grown in monoculture. The experiment was so successful that fungicidal sprays were no longer applied by the end of the two-year programme. Our results support the view that intraspecific crop diversification provides an ecological approach to disease control that can be highly effective over a large area and contribute to the sustainability of crop production.     

Chromatin organization is a major influence on regional mutation rates in human cancer cells

Cancer genome sequencing provides the first direct information on how mutation rates vary across the human genome in somatic cells. Testing diverse genetic and epigenetic features, here we show that mutation rates in cancer genomes are strikingly related to chromatin organization. Indeed, at the megabase scale, a single feature—levels of the heterochromatin-associated histone modification H3K9me3—can account for more than 40% of mutation-rate variation, and a combination of features can account for more than 55%. The strong association between mutation rates and chromatin organization is upheld in samples from different tissues and for different mutation types. This suggests that the arrangement of the genome into heterochromatin- and euchromatin-like domains is a dominant influence on regional mutation-rate variation in human somatic cells.     

Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA

Tandem-repetitive minisatellite regions in vertebrate DNA frequently show substantial allelic variation in the number of repeat units. This variation is thought to arise through processes such as unequal crossover or replication slippage. We show here that the spontaneous mutation rate to new length alleles at extremely variable human minisatellites is sufficiently high to be directly measurable in human pedigrees. The mutation rate at different loci increases with variability in accord with the neutral mutation/random drift hypothesis, and rises to 5% per gamete for the most unstable human minisatellite isolated. Mutations are sporadic, occur with similar frequencies in sperm and oocytes, and can involve the gain or loss of substantial numbers of repeat units, consistent with length changes arising primarily by unequal exchange at meiosis. Germline instability must therefore be taken into account when using hypervariable loci as genetic markers, particularly in pedigree analysis and parenthood testing.     

基于遗传算法的水轮发电机组模糊调速器的研究

针对水轮机调节系统模糊控制存在的问题 ,结合遗传算法在水轮机组控制中的应用现状 ,提出了一种采用遗传算法在线优化模糊隶属度函数的方法。仿真结果表明 ,该方法可以自适应地跟踪控制对象的参数变化 ,有效地对模糊控制器进行在线优化 ,从而为水轮发电机组的在线智能控制提供了一条有效途径     

Genetic control and evolution of sexually dimorphic characters in Drosophila

Sexually dimorphic abdominal pigmentation and segment morphology evolved recently in the melanogaster species group of the fruitfly Drosophila. Here we show that these traits are controlled by the bric à brac [corrected] (bab) gene, which integrates regulatory inputs from the homeotic and sex-determination pathways. bab expression is modulated segment- and sex-specifically in sexually dimorphic species, but is uniform in sexually monomorphic species. We suggest that bab has an ancestral homeotic function, and that regulatory changes at the bab locus played a key role in the evolution of sexual dimorphism. Pigmentation patterns specified by bab affect mating preferences, suggesting that sexual selection has contributed to the evolution of bab regulation.     

Evolution of digital organisms at high mutation rates leads to survival of the flattest.

Darwinian evolution favours genotypes with high replication rates, a process called 'survival of the fittest'. However, knowing the replication rate of each individual genotype may not suffice to predict the eventual survivor, even in an asexual population. According to quasi-species theory, selection favours the cloud of genotypes, interconnected by mutation, whose average replication rate is highest. Here we confirm this prediction using digital organisms that self-replicate, mutate and evolve. Forty pairs of populations were derived from 40 different ancestors in identical selective environments, except that one of each pair experienced a 4-fold higher mutation rate. In 12 cases, the dominant genotype that evolved at the lower mutation rate achieved a replication rate >1.5-fold faster than its counterpart. We allowed each of these disparate pairs to compete across a range of mutation rates. In each case, as mutation rate was increased, the outcome of competition switched to favour the genotype with the lower replication rate. These genotypes, although they occupied lower fitness peaks, were located in flatter regions of the fitness surface and were therefore more robust with respect to mutations.     

在内部演化硬件中实现自适应变异参数控制

为了在演化过程中优化演化算法性能和避免花费大量时间在演化算法的参数设定中,设计了一种新颖的基于硬件实现的自适应变异比率控制方法.为了实现自适应特性,变异比率控制参数也被编码到染色体中作为附加的基因经历演化操作.本方法的有效性将通过和传统的采用固定变异比率的演化算法在演化4-bit偶校验函数(even-parity function),2-bit乘法器和3-bit乘法器的对比实验中进行证明.实验平台建立在一个完全FPGA实现的内部演化硬件上,它的设计思想来源于笛卡尔遗传程序(Cartesian Genetic Programming).在所有实验中,基于自适应变异比率控制的演化算法的性能明显优于传统的采用固定变异比率的遗传算法.