DNA水平上检测正选择方法的研究进展

达尔文的自然选择学说指出, 自然选择作用是物种进化的主要因素。而1968年Kimura提出的中性进化学说认为中性突变和随机漂变才是进化的主要动力。在接下来的30多年时间中, 人们尝试从各种角度来检测自然选择是否存在。随着DNA测序技术的发展, 大量的DNA序列信息为检验自然选择提供了丰富的数据。因为自然选择会影响DNA变异模式, 所以可以通过分析现有的DNA样本来推断过去是否发生了自然选择。另一方面, 种群历史等因素也会影响到DNA变异模式, 因此会对自然选择的检测产生干扰。文章主要介绍了中性检验基本的概念, 全面回顾了一些经典的检验方法, 并着重介绍了近几年新发展出的研究方向。     

脊椎动物线粒体DNA的进化遗传学

近年来,在分子进化遗传学研究中又产生出一个新的生长点,这就是线粒体DNA(mtDNA)的进化遗传学研究。因为mtDNA结构简单,与拥有4×10~8到4×10~(11)个碱基对的多细胞动物的核基因组相比,比其最小者小25000倍;在不同物种间,mtDNA上的基因成分相对稳定,很少受到序列重排的影响;另一方面,mtDNA又具有广泛的种内和种间多态性,且为母性遗传,在亲缘关系相近的物种间其进化速度比核基因快,因而它为从分子水平上研究种群遗传学和进化遗传学提供了理想的研究对象。     

人类胎儿的性别选择属自然选择

现代人类的祖先在数百万年的演化史中,不断为适应自然,逐渐地向现代人进化。     

一种在核苷酸水平检测自然选择的新方法

非编码区序列在基因表达调控中起着重要作用,但其在进化过程中是否受到选择作用一直较难检测。最近有一些研究使用平均的核苷酸替换速率与中性序列的核苷酸替换速率的比值(ω)作为检测非编码区总体受选择作用的指标;但是对于非编码区而言,了解具体哪些核苷酸受到选择作用更具有意义。我们借鉴Nielsen&Yang(1998)检测单个氨基酸位点是否受选择作用的思路,在最大似然法的模型下,提出一种在核苷酸位点水平上对自然选择作用检测的方法。本方法能够检测在进化过程中对功能分化有重要贡献的核苷酸位点,包括编码和非编码区。将此方法应用于熟知的受到正选择作用的蛋白编码基因序列(HIV-1包装蛋白基因编码区),均能够检测到那些已知的受到正选择的核苷酸(密码子)位点,说明此方法可以有效地在核苷酸位点水平检测选择作用;又将此方法应用于非编码区(CTGF基因5′UTR),也得到了良好的结果。     

植物种群分子进化中对生境的适应——对荒漠植物遗传多样性研究结果的初步分析

长期以来,自然选择理论与中性理论对生物分子进化中的环境适应机理存在着激烈争论。目前,在植物种群分子进化中对生境适应的研究中正面临着一些难题：中性突变是分子水平进化的唯一原因,自然选择发挥主要作用的适应性进化是否存在于分子水平,选择与中性两种学说两种机制完全不同,如何才能将两者联系和统一起来,部分学者利用建立各种模型来描述自然选择对分子标记位点以及连锁序列的直接作用,如生态位宽度变异假设等。本研究小组以新疆阜康荒漠植物为研究对象,通过对两种重要荒漠植物遗传多样性的研究,分析两种植物各亚种群不同生境的生态因子与其遗传变异的关系,讨论生态位宽度变异假设,揭示遗传变异的产生与维持。中性论者与选择论者都试图解释生物环境适应与分子变异之间的关系。中性论和选择论是反映进化的两个侧面,它们不是绝对的,可以相互转化。     

“中性说”是非达尔文主义的吗？

“中性说”是非达尔文主义的吗？马刚（第四军医大学生物教研室,西安７１００３２）木村资生等人提出的“中性说”因直接违反了达尔文主义的核心一“自然选择说”,而被认为是作达尔文主义的．并由此引起了一场反对和维护达尔文主义的长时期的论战。迄今,论战仍在继续。...     

金丝猴属的DNA序列变异及进化与保护遗传学研究

金丝猴的分类及系统发育存在许多争议。本文测定了２只川金丝猴、８只滇金丝猴、１只越南金丝猴和１只灰叶猴的２５３ｂｐ的线粒体细胞色素ｂ基因的序列。其中４７个位点（１９％）检出变异。我们采用简约法、最大似然法和距离法构建了一系列的分子系统树,得到相同的拓扑结构,从而可能在分子水平澄清了金丝猴属的系统发育。结果表明,云南金丝猴与越南金丝猴间的关系较与川金丝猴的为近。金丝猴属的分化大约发生在２～６百万年以前。这３种金丝猴均是独立的种,且都应归入金丝猴属。对８只来自野外的滇金丝猴（其中包括了昆明动物研究所圈养群体的所有６只创立者）的非损伤性遗传分析提示,编号为ＹＫ２的母猴是维持该圈养群体遗传多样性的关键猴。我们建立的这种非损伤性遗传分析方法广泛适用于珍稀濒危动物的遗传多样性及遗传管理研究。     

路径依赖的选择——统一自然选择与中性选择

进化思想和方法论并行的、相互独立的自然选择理论和中性选择理论是否能够有效统一起来, 一直是理论生物学重点关注的问题, 而路径依赖的选择提供了一种可能。与中性选择理论一致, 路径依赖的选择也采用了完全对称性的前提假设——自然界的突变完全是基于统计随机性, 不具备方向性, 因而突变没有适合度的差异。但是在一些特定的时空环境下, 环境的正反馈效应导致中性选择对称性的破缺, 促使该突变产生递归效应——拉马克的主动选择或者获得性遗传效应, 这种适宜环境正反馈作用下的生物主动选择与环境自然选择压力下的被动选择产生相互拮抗作用, 并因此在多维的空间条件下形成路径。路径依赖的选择认为生物演化的过程将是一个路径频率的选择过程而不是适合度提高的过程, 并强烈依赖于其历史上所经历的事件或者环境变化等外界条件; 由于不同演化路径之间存在转移概率(比如生物演化中的质粒转移、转座子、生态过程相互作用等), 路径的演化会存在加速或者减速效应, 解释了古尔德等主张的间断平衡论。当环境选择压力很小或者为零的时候, 多数或者所有路径都等价(类似中性选择结果); 而随着环境压力的增大, 不同路径的频率将差异化, 且路径频率比较高的更容易被选择。当环境压力很大, 历史事件等外界因素或者演化过程对路径本身的演化没有影响的时候(静态的、均衡状态), 频率最高的那条路径就是演化所用时间最短或者最优的路径——达尔文自然选择理论的结果。在借鉴了现代物理学, 尤其是量子力学所用的路径积分方法, 路径依赖的选择也许为我们提供了一个不同的视角和方法来解释生物的演化过程。     

真核生物DNA的进化

真核生物ＤＮＡ的进化刘振山（河北省张家口市教委科学研究室０７５０３１）生物在进化过程中的演变都是由ＤＮＡ的自发改变开始的,当生物从简单形式进化到较复杂的形式后,基因组无论是在遗传物质ＤＮＡ的含量上,还是在基因的数目上都有所扩大,遗传物质的这种量和质的...     

鱼类线粒体DNA及其在分子群体遗传研究中的应用

鱼类是脊椎动物亚门中种属数量最多的类群,分布广泛,起源复杂,拥有丰富的遗传多样性.多种自然和人为因素对鱼类遗传资源存在不同程度的作用,对鱼类生存和进化有重要影响.采用分子手段探讨鱼类遗传资源现状,可为遗传育种、鱼类进化研究和遗传资源保护等提供一定科学依据.以鱼类线粒体DNA(mtDNA)为代表的分子标记技术已被用于研究鱼类群体遗传结构及其与影响因素间的关系.本文综述了鱼类mtDNA的结构特征及其在鱼类分子群体遗传研究中的应用,对了解和运用mtDNA等分子标记研究鱼类群体遗传具有一定参考价值.     

Polite DNA: Functional density and functional compatibility in genomes

Summary Certain as yet poorly defined functions of DNA appear to involve collectively domain-sized sequences. It is proposed that most sequence segments within a domain may be either functionally superfluous or instrumental, depending on how many related sequences are present in the domain. When redundant and functionally dispensable, such DNA segments presumably still have to conform to compositional or sequence-motif patterns that characterize the domain. In its relations with neighboring sequences, such DNA is required to be polite. Polite DNA is DNA that, without being crucially involved in function, is subject to constraints of conformity and, through its base composition, respects a function for which it is not required. This concept is developed by contrasting the distribution of specific and general functions over DNA with this distribution as found in proteins and by distinguishing functional compatibility from pivotal functionality. The sequence constraints to which heterochromatin as well as, apparently, long interspersed repetitive sequences are known to be subject seem to imply that DNA, even when it does not carry out a pivotal function, is indeed, at the very least, required to be polite.Presented at the FEBS Symposium on Genome Organization and Evolution, held in Crete, Greece, September 1–5, 1986     

Darwin's concept of final cause: neither new nor trivial

Darwin'suse of final cause accords with the Aristotelian idea of finalcauses as explanatory types – as opposed to mechanical causes, which arealways particulars. In Wright's consequence etiology, anadaptation is explained by particular events, namely, its past consequences;hence, that etiology is mechanistic at bottom. This justifies Ghiselin'scharge that such versions of teleology trivialize the subject, But a purelymechanistic explanation of an adaptation allows it to appear coincidental.Patterns of outcome, whether biological or thermodynamic, cannot be explainedbytracing causal chains, even were that possible. They are explicanda of aspecialkind. The form of their explanation, in statistical mechanics or by naturalselection, is not captured by statistical variants of the covering-law model orrelated models of explanation. In them as in classical teleology, types ofoutcome are cited to explain why there are outcomes of those types. But onlywhen types are explanatory by being selected for, as inexplanations of animal and human behavior as well as in Darwin's theory ofnatural selection, but not in statistical mechanics, is the explanationteleological. Darwin's theory is nontrivially teleological.     

Genetic variation: molecular mechanisms and impact on microbial evolution

On the basis of established knowledge of microbial genetics one can distinguish three major natural strategies in the spontaneous generation of genetic variations in bacteria. These strategies are: (1) small local changes in the nucleotide sequence of the genome, (2) intragenomic reshuffling of segments of genomic sequences and (3) the acquisition of DNA sequences from another organism. The three general strategies differ in the quality of their contribution to microbial evolution. Besides a number of non-genetic factors, various specific gene products are involved in the generation of genetic variation and in the modulation of the frequency of genetic variation. The underlying genes are called evolution genes. They act for the benefit of the biological evolution of populations as opposed to the action of housekeeping genes and accessory genes which are for the benefit of individuals. Examples of evolution genes acting as variation generators are found in the transposition of mobile genetic elements and in so-called site-specific recombination systems. DNA repair systems and restriction-modification systems are examples of modulators of the frequency of genetic variation. The involvement of bacterial viruses and of plasmids in DNA reshuffling and in horizontal gene transfer is a hint for their evolutionary functions. Evolution genes are thought to undergo biological evolution themselves, but natural selection for their functions is indirect, at the level of populations, and is called second-order selection. In spite of an involvement of gene products in the generation of genetic variations, evolution genes do not programmatically direct evolution towards a specific goal. Rather, a steady interplay between natural selection and mixed populations of genetic variants gives microbial evolution its direction.     

Natural hierarchy emerges from energy dispersal

Hierarchical organization of ‘systems within systems’ is an apparent characteristic of nature. For many biotic and abiotic systems it is known how the nested structural and functional order builds up, yet the general principle why matter evolves to hierarchies has remained unfamiliar to many. We clarify that increasingly larger integrated systems result from the quest to decrease free energy according to the 2nd law of thermodynamics. The argumentation is based on the recently derived equation of motion for natural processes. Hierarchically organized energy transduction machinery emerges naturally when it provides increased rates of energy dispersal. Likewise, a hierarchical system will dismantle into its constituents when they as independent systems will provide higher rates of entropy increase. Since energy flows via interactions, decreasing strengths of interactions over increasingly larges lengths scales mark natural boundaries for nested integrated systems.     

Wheat storage proteins: glutenin DNA diversity in wild emmer wheat,Triticum dicoccoids,in Israel and Turkey. 3. Environmental correlates and allozymic associations

The diversity of high-molecular-weight (HMW) and low-molecular-weight (LMW) glutenin subunits in the tetraploid wild progenitor of wheat, Triticum dicoccoides, was studied at the DNA level by the polymerase chain reaction (PCR). The DNA diversity of HMW and LMW glutenins was shown to be correlated to environmental physical and biotic factors (climate, soil and pathogen resistance) and to allozyme variation. We conclude that glutenin DNA diversity is nonrandomly distributed and could be more optimally sampled in nature for future breeding programmes to improve bread quality.     

DNA动力学柔性的统计力学模型

考虑碱基对之间的非紧邻相互作用、涨落的序列依赖效应和非对称涨落,提出了DNA构象的统计力学模型,给出了DNA柔性的新定义。作为模型的应用,对12种三核苷酸重复序列的动力学柔性作了预测。理论预测与其它方法得到的结论比较,有很好的一致性。对模型和结论的理论意义作了讨论。     

Sexual selection: Another Darwinian process

Why was sexual selection so important to Darwin? And why was it de-emphasized by almost all of Darwin's followers until the second half of the 20th century? These two questions shed light on the complexity of the scientific tradition named “Darwinism”. Darwin's interest in sexual selection was almost as old as his discovery of the principle of natural selection. From the beginning, sexual selection was just another “natural means of selection”, although different from standard “natural selection” in its mechanism. But it took Darwin 30 years to fully develop his theory, from the early notebooks to the 1871 book The Descent of Man, and Selection in Relation to Sex. Although there is a remarkable continuity in his basic ideas about sexual selection, he emphasized increasingly the idea that sexual selection could oppose the action of natural selection and be non adaptive. In time, he also gave more weight to mate choice (especially female choice), giving explicit arguments in favor of psychological notions such as “choice” and “aesthetic sense”. But he also argued that there was no strict demarcation line between natural and sexual selection, a major difficulty of the theory from the beginning. Female choice was the main reason why Alfred Russel Wallace, the co-discoverer of the principle of natural selection, engaged in a major controversy with Darwin about sexual selection. Wallace was suspicious about sexual selection in general, trying to minimize it by all sorts of arguments. And he denied entirely the existence of female choice, because he thought that it was both unnecessary and an anthropomorphic notion. This had something to do with his spiritualist convictions, but also with his conception of natural selection as a sufficient principle for the evolutionary explanation of all biological phenomena (except for the origin of mind). This is why Wallace proposed to redefine Darwinism in a way that excluded Darwin's principle of sexual selection. The main result of the Darwin–Wallace controversy was that most Darwinian biologists avoided the subject of sexual selection until at least the 1950 s, Ronald Fisher being a major exception. This controversy still deserves attention from modern evolutionary biologists, because the modern approach inherits from both Darwin and Wallace. The modern approach tends to present sexual selection as a special aspect of the theory of natural selection, although it also recognizes the big difficulties resulting from the inevitable interaction between these two natural processes of selection. And contra Wallace, it considers mate choice as a major process that deserves a proper evolutionary treatment. The paper's conclusion explains why sexual selection can be taken as a test case for a proper assessment of “Darwinism” as a scientific tradition. Darwin's and Wallace's attitudes towards sexual selection reveal two different interpretations of the principle of natural selection: Wallace's had an environmentalist conception of natural selection, whereas Darwin was primarily sensitive to the element of competition involved in the intimate mechanism of any natural process of selection. Sexual selection, which can lack adaptive significance, reveals this exemplarily.     

Inference on the strength of balancing selection for epistatically interacting loci

Existing inference methods for estimating the strength of balancing selection in multi-locus genotypes rely on the assumption that there are no epistatic interactions between loci. Complex systems in which balancing selection is prevalent, such as sets of human immune system genes, are known to contain components that interact epistatically. Therefore, current methods may not produce reliable inference on the strength of selection at these loci. In this paper, we address this problem by presenting statistical methods that can account for epistatic interactions in making inference about balancing selection. A theoretical result due to Fearnhead (2006) is used to build a multi-locus Wright-Fisher model of balancing selection, allowing for epistatic interactions among loci. Antagonistic and synergistic types of interactions are examined. The joint posterior distribution of the selection and mutation parameters is sampled by Markov chain Monte Carlo methods, and the plausibility of models is assessed via Bayes factors. As a component of the inference process, an algorithm to generate multi-locus allele frequencies under balancing selection models with epistasis is also presented. Recent evidence on interactions among a set of human immune system genes is introduced as a motivating biological system for the epistatic model, and data on these genes are used to demonstrate the methods.     

Selection for Chromosome Architecture in Bacteria

Bacterial chromosomes are immense polymers whose faithful replication and segregation are crucial to cell survival. The ability of proteins such as FtsK to move unidirectionally toward the replication terminus, and direct DNA translocation into the appropriate daughter cell during cell division, requires that bacterial genomes maintain an architecture for the orderly replication and segregation of chromosomes. We suggest that proteins that locate the replication terminus exploit strand-biased sequences that are overrepresented on one DNA strand, and that selection increases with decreased distance to the replication terminus. We report a generalized method for detecting these architecture imparting sequences (AIMS) and have identified AIMS in nearly all bacterial genomes. Their increased abundance on leading strands and decreased abundance on lagging strands toward replication termini are not the result of changes in mutational bias; rather, they reflect a gradient of long-term positive selection for AIMS. The maintenance of the pattern of AIMS across the genomes of related bacteria independent of their positions within individual genes suggests a well-conserved role in genome biology. The stable gradient of AIMS abundance from replication origin to terminus suggests that the replicore acts as a target of selection, where selection for chromosome architecture results in the maintenance of gene order and in the lack of high-frequency DNA inversion within replicores. [Reviewing Editor: Dr. Martin Kreitman]     

Animals in science education—ethics and alternatives

Increasingly, moral objections are being voiced to the use or killing of animals for educational purposes, and students' opinions are reflecting this. An animal rights philosophy often underlies these objections, but many people are unaware of the logic of the animal rights position, which is often dismissed as sentimentalism or anthropomorphism. While it is now possible to take A-level biology without undertaking dissection, there are many potential undergraduate students who would like to do courses in biology, medicine, pharmacology, physiology, and nursing, but are dissuaded by the animal use involved. Such students are frequently not offered non-animal options and risk being marked down in course work and exams, even though considerable advances have been made in the development of alternative teaching aids. This article summarizes the animal rights argument, and reviews some of the alternative approaches and their teaching effectiveness.