The Drosophila melanogaster Genetic Reference Panel

A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.     

Maintaining a behaviour polymorphism by frequency-dependent selection on a single gene

Accounting for the abundance of genetic variation in the face of natural selection remains a central problem of evolutionary biology. Genetic polymorphisms are constantly arising through mutation, and although most are promptly eliminated, polymorphisms in functionally important traits are common. One mechanism that can maintain polymorphisms is negative frequency-dependent selection on alternative alleles, whereby the fitness of each decreases as its frequency increases. Examples of frequency-dependent selection are rare, especially when attempting to describe the genetic basis of the phenotype under selection. Here we show frequency-dependent selection in a well-known natural genetic polymorphism affecting fruitfly foraging behaviour. When raised in low nutrient conditions, both of the naturally occurring alleles of the foraging gene (for(s) and for(R)) have their highest fitness when rare-the hallmark of negative frequency-dependent selection. This effect disappears at higher resources levels, demonstrating the role of larval competition. We are able to confirm the involvement of the foraging gene by showing that a sitter-like mutant allele on a rover background has similar frequency-dependent fitness as the natural sitter allele. Our study represents a clear demonstration of frequency-dependent selection, and we are able to attribute this effect to a single, naturally polymorphic gene known to affect behaviour.     

Sexually antagonistic genetic variation for fitness in red deer

Evolutionary theory predicts the depletion of genetic variation in natural populations as a result of the effects of selection, but genetic variation is nevertheless abundant for many traits that are under directional or stabilizing selection. Evolutionary geneticists commonly try to explain this paradox with mechanisms that lead to a balance between mutation and selection. However, theoretical predictions of equilibrium genetic variance under mutation-selection balance are usually lower than the observed values, and the reason for this is unknown. The potential role of sexually antagonistic selection in maintaining genetic variation has received little attention in this debate, surprisingly given its potential ubiquity in dioecious organisms. At fitness-related loci, a given genotype may be selected in opposite directions in the two sexes. Such sexually antagonistic selection will reduce the otherwise-expected positive genetic correlation between male and female fitness. Both theory and experimental data suggest that males and females of the same species may have divergent genetic optima, but supporting data from wild populations are still scarce. Here we present evidence for sexually antagonistic fitness variation in a natural population, using data from a long-term study of red deer (Cervus elaphus). We show that male red deer with relatively high fitness fathered, on average, daughters with relatively low fitness. This was due to a negative genetic correlation between estimates of fitness in males and females. In particular, we show that selection favours males that carry low breeding values for female fitness. Our results demonstrate that sexually antagonistic selection can lead to a trade-off between the optimal genotypes for males and females; this mechanism will have profound effects on the operation of selection and the maintenance of genetic variation in natural populations.     

Dissecting the architecture of a quantitative trait locus in yeast

Most phenotypic diversity in natural populations is characterized by differences in degree rather than in kind. Identification of the actual genes underlying these quantitative traits has proved difficult. As a result, little is known about their genetic architecture. The failures are thought to be due to the different contributions of many underlying genes to the phenotype and the ability of different combinations of genes and environmental factors to produce similar phenotypes. This study combined genome-wide mapping and a new genetic technique named reciprocal-hemizygosity analysis to achieve the complete dissection of a quantitative trait locus (QTL) in Saccharomyces cerevisiae. A QTL architecture was uncovered that was more complex than expected. Functional linkages both in cis and in trans were found between three tightly linked quantitative trait genes that are neither necessary nor sufficient in isolation. This arrangement of alleles explains heterosis (hybrid vigour), the increased fitness of the heterozygote compared with homozygotes. It also demonstrates a deficiency in current approaches to QTL dissection with implications extending to traits in other organisms, including human genetic diseases.     

Relative fitness can decrease in evolving asexual populations of S. cerevisiae

It is generally accepted from the darwinian theory of evolution that a progressive increase in population adaptation will occur in populations containing genetic variation in fitness, until a stable equilibrium is reached and/or the additive genetic variation is exhausted. However, the theoretical literature of population genetics documents exceptions where mean population fitness may decrease in response to evolutionary changes in gene frequency, due to varying selective coefficients, sexual selection or to epistatic interactions between loci. Until now, no examples of such exceptions have been documented from fitness estimates in either natural or experimental populations. We present here direct evidence that, as a result of epistatic interactions between adaptive mutations, mean population fitness can decrease in asexual evolving populations of the yeast Saccharomyces cerevisiae.     

Testing the genetics underlying the co-evolution of mate choice and ornament in the wild

One of the most debated questions in evolutionary biology is whether female choice of males with exaggerated sexual displays can evolve as a correlated response to selection acting on genes coding for male attractiveness or high overall viability. To date, empirical studies have provided support for parts of this scenario, but evidence for all key genetic components in a natural population is lacking. Here we use animal-model quantitative genetic analysis on data from over 8,500 collared flycatchers (Ficedula albicollis) followed for 24 years to quantify all of the key genetic requirements of both fisherian and 'good-genes' models on sexual selection in the wild. We found significant additive genetic variances of all the main components: male ornament (forehead patch size), female mate choice for this ornament, male fitness and female fitness. However, when the necessary genetic correlations between these components were taken into account, the estimated strength of indirect sexual selection on female mate choice was negligible. Our results show that the combined effect of environmental influences on several components reduces the potential for indirect sexual selection in the wild. This study provides insight into the field of sexual selection by showing that genes coding for mate choice for an ornament probably evolve by their own pathways instead of 'hitchhiking' with genes coding for the ornament.     

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.     

Hybridization and adaptive mate choice in flycatchers

Hybridization in natural populations is strongly selected against when hybrid offspring have reduced fitness. Here we show that, paradoxically, pairing with another species may offer the best fitness return for an individual, despite reduced fitness of hybrid offspring. Two mechanisms reduce the costs to female collared flycatchers of pairing with male pied flycatchers. A large proportion of young are sired by conspecific male collared flycatchers through extra-pair copulations, and there is a bias in favour of male offspring (which, unlike females, are fertile) within hybrid pairs. In combination with temporal variation in breeding success, these cost-reducing mechanisms yield quantitative predictions about when female collared flycatchers should accept a male pied flycatcher as a mate; empirical data agree with these predictions. Apparent hybridization may thus represent adaptive mate choice under some circumstances.     

动态复杂性状遗传结构研究的统计模型

许多重要的农艺性状、生物学和生物医学性状都是数量性状，这些性状在不同的发育阶段发生变化，并表现出复杂的动态特征。针对这些动态性状，传统的遗传作图方法是通过在不同的年龄或发育阶段利用遗传标记与表型性状进行关联分析，并比较这些性状在不同发育阶段的差异，或者通过进行不同阶段的多位点作图进行分析。然而，这些方法并不能确切地反映整个发育过程和动态特点，这使得对性状遗传结构的推测受到限制。要克服这一困难，函数作图将为动态性状的遗传学研究提供一条有效的途径。函数作图综合了生物学机制的数学特性和性状遗传作图的统计学特点，结合统计模型、遗传学和发育生物学的函数作图策略，力求解决诸如发育的遗传控制模式、QTL的持续效应以及引起发育过程中启动和终止的遗传机制等问题。笔者提出的函数作图策略将提供一个研究基因作用及互作与发育模式之间有效的量化检测平台。     

Frequency-dependent survival in natural guppy populations

The maintenance of genetic variation in traits under natural selection is a long-standing paradox in evolutionary biology. Of the processes capable of maintaining variation, negative frequency-dependent selection (where rare types are favoured by selection) is the most powerful, at least in theory; however, few experimental studies have confirmed that this process operates in nature. One of the most extreme, unexplained genetic polymorphisms is seen in the colour patterns of male guppies (Poecilia reticulata). Here we manipulated the frequencies of males with different colour patterns in three natural populations to estimate survival rates, and found that rare phenotypes had a highly significant survival advantage compared to common phenotypes. Evidence from humans and other species implicates frequency-dependent survival in the maintenance of molecular, morphological and health-related polymorphisms. As a controlled manipulation in nature, this study provides unequivocal support for frequency-dependent survival--an evolutionary process capable of maintaining extreme polymorphism.     

遗传算法及其在TSP中的应用

本文详述遗传算法的起源、实现、及应用和存在的问题。遗传算法是仿自然界的自然选择法则设计的。算法源于一群随机基因组，通过一定的适应性判决消除适应性低的基因组，保留适应性中等的和高的基因组；并在高适应性的基因组中，随机进行变异和组配，将基因组补足到恒定的数量，再进行适应性判决，一直到满足问题的要求。本文就此法做了中国旅行商题，实验效果非常满意，产生的结果比用Ｈｏｐｆｉｅｌｄ神经网络计算结果要好得多。     

Evolvability of an RNA virus is determined by its mutational neighbourhood

The ubiquity of mechanisms that generate genetic variation has spurred arguments that evolvability, the ability to generate adaptive variation, has itself evolved in response to natural selection. The high mutation rate of RNA viruses is postulated to be an adaptation for evolvability, but the paradox is that whereas some RNA viruses evolve at high rates, others are highly stable. Here we show that evolvability in the RNA bacteriophage phi6 is also determined by the accessibility of advantageous genotypes within the mutational neighbourhood (the set of mutants one or a few mutational steps away). We found that two phi6 populations that were derived from a single ancestral phage repeatedly evolved at different rates and toward different fitness maxima. Fitness measurements of individual phages showed that the fitness distribution of mutants differed between the two populations. Whereas population A, which evolved toward a higher maximum, had a distribution that contained many advantageous mutants, population B, which evolved toward a lower maximum, had a distribution that contained only deleterious mutants. We interpret these distributions to measure the fitness effects of genotypes that are mutationally available to the two populations. Thus, the evolvability of phi6 is constrained by the distribution of its mutational neighbours, despite the fact that this phage has the characteristic high mutation rate of RNA viruses.     

拟南芥突变体与基因功能研究

当前,突变体已成为功能生物学研究的重要工具.文章综述了模式植物拟南芥在群体遗传变异、自发突变体表型、人工突变体库构建、突变体基因功能分析等方面取得的进展.拟南芥突变体的研究能促进其在功能、进化上的了解,更有助于其他高等植物的基因功能分析。     

Molecular and phenotypic variation in the achaete-scute region of Drosophila melanogaster

Variation in quantitative characters underlies much adaptive evolution and provides the basis for selective improvement of domestic species, yet the genetic nature of quantitative variation is poorly understood. Many loci affecting quantitative traits have been identified by the segregation of mutant alleles with major qualitative effects. These alleles may represent an extreme of a continuum of allelic effects, and most quantitative variation could result from the segregation of alleles with subtle effects at loci identified by alleles with major effects. The achaete-scute complex in Drosophila melanogaster plays a central part in bristle development and has been characterized at the molecular level. The hypothesis that naturally occurring quantitative variation in bristle number could be associated with wild-type alleles of achaete-scute was tested by correlating phenotypic variation in bristle number with molecular variation in restriction maps in this region among chromosomes extracted from natural populations. DNA insertion variation in the achaete-scute region was found to be strongly associated with variation in bristle number.     

分子标记辅助选择在植物育种中的应用与前瞻

植物育种项目包括两方面的重要工作，首先是确定育种材料中是否存在有用的遗传变异，其次是采用有效的方法把目标基因转移到品种中。分子育种包括分子标记辅助选择(MAS)和利用基因工程手段育种。选择是指在一个群体中选择符合需要的基因型，它是育种中最重要的环节之一。在传统育种中，选择的依据通常是表现型，从表现型推断基因型。表型选择对寡基因控制的质量性状较为有效，而时多基因控制的数量性状则效率不高。随着现代分子生物学的迅速发展，分子标记辅助选择技术为实现对基因型的直接选择提供了可能。阐述了分子标记辅助选择(MAS)的应用研究，讨论了MAS存在的问题以及发展前景和展望。     

A yeast prion provides a mechanism for genetic variation and phenotypic diversity

A major enigma in evolutionary biology is that new forms or functions often require the concerted effects of several independent genetic changes. It is unclear how such changes might accumulate when they are likely to be deleterious individually and be lost by selective pressure. The Saccharomyces cerevisiae prion [PSI+] is an epigenetic modifier of the fidelity of translation termination, but its impact on yeast biology has been unclear. Here we show that [PSI+] provides the means to uncover hidden genetic variation and produce new heritable phenotypes. Moreover, in each of the seven genetic backgrounds tested, the constellation of phenotypes produced was unique. We propose that the epigenetic and metastable nature of [PSI+] inheritance allows yeast cells to exploit pre-existing genetic variation to thrive in fluctuating environments. Further, the capacity of [PSI+] to convert previously neutral genetic variation to a non-neutral state may facilitate the evolution of new traits.     

Physical performance and Darwinian fitness in lizards

Strong evidence for a genetic basis of variation in physical performance has accumulated. Considering one of the basic tenets of evolutionary physiology--that physical performance and darwinian fitness are tightly linked--one may expect phenotypes with exceptional physiological capacities to be promoted by natural selection. Why then does physical performance remain considerably variable in human and other animal populations? Our analysis of locomotor performance in the common lizard (Lacerta vivipara) demonstrates that initial endurance (running time to exhaustion measured at birth) is indeed highly heritable, but natural selection in favour of this trait can be unexpectedly weak. A manipulation of dietary conditions unravels a proximate mechanism explaining this pattern. Fully fed individuals experience a marked reversal of performance within only one month after birth: juveniles with low endurance catch up, whereas individuals with high endurance lose their advantage. In contrast, dietary restriction allows highly endurant neonates to retain their locomotor superiority as they age. Thus, the expression of a genetic predisposition to high physical performance strongly depends on the environment experienced early in life.     

遗传规划算法的改进研究

通过改变遗传规划算法在生成初始群体时的方法,调整变异概率,修正适应度函数,对遗传规划算法进行改进,使生成的初始群体具有良好的性能;并通过两个函数进行符号验证,说明改进后的方法是有效可行的。     

Sex increases the efficacy of natural selection in experimental yeast populations

Why sex evolved and persists is a problem for evolutionary biology, because sex disrupts favourable gene combinations and requires an expenditure of time and energy. Further, in organisms with unequal-sized gametes, the female transmits her genes at only half the rate of an asexual equivalent (the twofold cost of sex). Many modern theories that provide an explanation for the advantage of sex incorporate an idea originally proposed by Weismann more than 100 years ago: sex allows natural selection to proceed more effectively because it increases genetic variation. Here we test this hypothesis, which still lacks robust empirical support, with the use of experiments on yeast populations. Capitalizing on recent advances in the molecular biology of recombination in yeast, we produced by genetic manipulation strains that differed only in their capacity for sexual reproduction. We show that, as predicted by the theory, sex increases the rate of adaptation to a new harsh environment but has no measurable effect on fitness in a new benign environment where there is little selection.