Ephestia: the experimental design of Alfred Kühn''s physiological developmental genetics

Much of the early history of developmental and physiological genetics in Germany remains to be written. Together with Carl Correns and Richard Goldschmidt, Alfred Kühn occupies a special place in this history. Trained as a zoologist in Freiburg im Breisgau, he set out to integrate physiology, development and genetics in a particular experimental system based on the flour moth Ephestia kühniella Zeller. This paper is meant to reconstruct the crucial steps in the experimental pathway that led Kühn and his collaborators at the University of Göttingen, and later at the Kaiser Wilhelm Institutes of Biology and Biochemistry in Berlin, to formulate, in their specific way, what later became known as the “one gene – one enzyme hypothesis.” Special attention will be given to the interaction of the different parts of Kühn's Ephestia-based project, which were rooted in different research traditions. The paper retraces how, roughly between 1925 and 1945, these elements came to form a mixed experimental set-up composed of genetic, embryological, physiological and, finally, biochemical constituents. Accordingly, emphasis is laid on the development of the terminology in which the results were cast, and how it reflected the hybrid state of an experimental system successively acquiring new epistemic layers.     

Mendelian inheritance in Germany between 1900 and 1910. The case of Carl Correns (1864-1933)

Carl Correns (1864-1933) came to recognize Mendel's rules between 1894 and 1900 while trying to find out the mechanism of xenia, that is, the direct influence of the fertilizing pollen on the mother plant in maize and peas among other species. In this paper, I am concerned with the ten years of Correns' work after the annus mirabilis of 1900 until 1910, when the main outlines of the new science of genetics had been established. It is generally assumed that after 1900 Correns quickly began probing the limits of Mendelian inheritance, both as far as the explanatory force of formal transmission genetics and the generality of Mendel's laws are concerned. A careful examination of his papers however shows that he was much more interested in the scope of Mendelian inheritance than in its limits. Even his work with variegated Mirabilis plants, which historiographical folklore still presents as a result of Correns' growing interest in cytoplasmic inheritance, can be shown to have been conducted to corroborate just the opposite, namely, the validity of the nuclear paradigm. The paper will show that Correns' research results in those years (among them the Mendelian inheritance of sex in higher plants) were the outcome of a complex experimental program which involved breeding experiments with dozens of different species.     

Erwin Baur or Carl Correns: who really created the theory of plastid inheritance?

Historical reviews of the field of non-Mendelian genetics and many other publications credit Erwin Baur and Carl Correns equally for the development of the theory of plastid inheritance. However, a study of the original literature indicates that this conclusion is not correct. Analysis of the relevant articles leads to the conclusion that Baur alone deserves credit for the theory of plastid inheritance. In his classic article on the inheritance properties of white-margined Pelargonium plants, Baur (1909) stated: (1) The plastids are carriers of hereditary factors which are able to mutate. (2) In variegated plants, random sorting-out of plastids is taking place. (3) The genetic results indicate a biparental inheritance of plastids by egg cells and sperm cells in Pelargonium. By contrast, Correns held the view that in variegated plants there is a maternally transmitted labile state of the cytoplasm which switches either to a permanently "healthy" state (allowing the "indifferent" plastids to become green chloroplasts) or to a permanently "diseased, ill" cytoplasmic state (causing white plastids and cells). Otto Renner supported Baur's theory and worked out important characteristics of plastid inheritance in the genus Oenothera. In the 1930s Renner reported many more observations, which established plastid inheritance as a widely accepted genetic theory.     

Hugo De Vries: from the theory of intracellular pangenesis to the rediscovery of Mendel

On the basis of the article by the Dutch botanist Hugo De Vries 'On the law of separation of hybrids' published in the Reports of the Académie des Sciences in 1900, and the beginning of the controversy about priority with Carl Correns and Erich von Tschermak, I consider the question of the posthumous influence of the Mendel paper. I examine the construction of the new theoretical framework which enabled its reading in 1900 as a clear and acceptable presentation of the rules of the transmission of hereditary characters. In particular, I analyse the introduction of the idea of determinants of organic characters, understood as separable material elements which can be distributed randomly in descendants. Starting from the question of heredity, such as it was defined by Darwin in 1868, and after its critical developments by August Weismann, Hugo De Vries was able to suggest such an idea in his Intracellular Pangenesis. He then laid out a programme of research which helps us to understand the 'rediscovery' published in 1900.     

The foundation of extranuclear inheritance: plastid and mitochondrial genetics

In 1909 two papers by Correns and by Baur published in volume 1 of Zeitschrift für induktive Abstammungs- und Vererbungslehre (now Molecular Genetics and Genomics) reported on the non-Mendelian inheritance of chlorophyll deficiencies. These papers, reporting the very first cases of extranuclear inheritance, laid the foundation for a new field: non-Mendelian or extranuclear genetics. Correns observed a purely maternal inheritance (in Mirabilis), whereas Baur found a biparental inheritance (in Pelargonium). Correns suspected the non-Mendelian factors in the cytoplasm, while Baur believed that the plastids carry these extranuclear factors. In the following years, Baur’s hypothesis was proved to be correct. Baur subsequently developed the theory of plastid inheritance. In many genera the plastids are transmitted only uniparentally by the mother, while in a few genera there is a biparental plastid inheritance. Commonly there is random sorting of plastids during ontogenetic development. Renner and Schwemmle as well as geneticists in other countries added additional details to this theory. Pioneering studies on mitochondrial inheritance in yeast started in 1949 in the group of Ephrussi and Slonimski; respiration-deficient cells (petites in yeast, poky in Neurospora) were demonstrated to be due to mitochondrial mutations. Electron microscopical and biochemical studies (1962–1964) showed that plastids and mitochondria contain organelle-specific DNA molecules. These findings laid the molecular basis for the two branches of extranuclear inheritance: plastid and mitochondrial genetics.     

Armin von Tschermak-Seysenegg (1870–1952): Physiologist and Co-‘Rediscoverer’ of Mendel’s laws

The ‘rediscovery’ of Mendel’s laws in 1900 was a turning point in modern research of heredity/genetics. According to the traditional view, adopted and fostered by many textbooks of genetics, Mendel’s principles were presented in the first half of 1900 simultaneously and independently by three biologists (H. de Vries, C. Correns, E. v. Tschermak-Seysenegg). Having thus laid the foundations of further development, the ‘rediscovery’ continues to attract considerable interest. Since the 1950s, however, serious questions arose concerning both the chronology and specific conceptual achievement of the scientists involved. Not only the independence but also parallelism was analysed in the context of individual research programmes of these three scholars. The youngest of them, Erich v. Tschermak-Seysenegg, was even excluded from the list of ‘rediscoverers’. The aim of this paper is to use new archival evidence and approximate the contribution of the physiologist and ophthalmologist Armin von Tschermak-Seysenegg (1870–1952) to the events of 1900 and 1901.     

The genetics of human drug response

The genetics of variable drug response appears to be a more tractable complex trait than common disease predisposition. This has implications for prioritizing research and for experimental design, and in particular argues for extensive use of candidate gene based approaches in pharmacogenetic association studies. Eventually, when whole genome scanning becomes feasible, it may be appropriate to consider weighting schemes that assign higher prior probabilities of variants in genes related to the mode of action of metabolism of medicines.     

基因组文库构建及其在保护遗传学中的应用前景

基因组文库是进行分子克隆和基因组结构与功能研究的基础。完整的基因组文库的构建, 使任何DNA 片段的筛选和获得成为可能。随着不同克隆载体的相继出现, 基因组文库也经历了一系列的发展过程。其中, BAC文库因其转化效率高、嵌合体少、插入片段易回收, 以及容载量较大等优点而被广泛应用。近几十年来, 随着环境的日益恶化、分子遗传学技术的迅速发展, 以及保护生物学和分子遗传学的不断相互渗透, 孕育产生了保护遗传学这一分支学科。作为保护遗传学中物种保护策略的重要部分, 建立濒危野生动植物的基因组文库, 是保存其种质资源的最为有效的实际手段和方法, 并能为进一步开展与生殖、疾病和重要经济性状等方面有关的功能基因的研究, 提供可靠的材料保证。     

Using historical captive stocks in conservation. The case of␣the␣lesser white-fronted goose

Many captive stocks of economically or otherwise valuable species were established before the decline of the wild population. These stocks are potentially valuable sources of genetic variability, but their taxonomic identity and actual value is often uncertain. We studied the genetics of captive stocks of the threatened lesser white-fronted goose Anser erythropus maintained in Sweden and elsewhere in Europe. Analyses of mtDNA and nuclear microsatellite markers revealed that 36% of the individuals had a hybrid ancestry. Because the parental species are closely related it is unlikely that our analyses detected all hybrid individuals in the material. Because no ancestral polymorphism or introgression was observed in samples of wild populations, it is likely that the observed hybridisation has occurred in captivity. As a consequence of founder effect, drift and hybridisation, captive stocks were genetically differentiated from the wild populations of the lesser white-fronted goose. The high level of genetic diversity in the captive stocks is explained at least partially by hybridisation. The present captive stocks of the lesser white-fronted goose are considered unsuitable for further reintroduction, or supplementation: hybridisation has involved three species, the number of hybrids is high, and all the investigated captive stocks are similarly affected. The results highlight the potential shortcomings of using captive-bred individuals in supplementation and reintroduction projects, when the captive stocks have not been pedigreed and bred according to conservation principles. Deceased 20 March 2004.     

Molecular systematics and population genetics of biological invasions: towards a better understanding of invasive species management

The study of population genetics of invasive species offers opportunities to investigate rapid evolutionary processes at work, and while the ecology of biological invasions has enjoyed extensive attention in the past, the recentness of molecular techniques makes their application in invasion ecology a fairly new approach. Despite this, molecular biology has already proved powerful in inferring aspects not only relevant to the evolutionary biologist but also to those concerned with invasive species management. Here, we review the different molecular markers routinely used in such studies and their application(s) in addressing different questions in invasion ecology. We then review the current literature on molecular genetic studies aimed at improving management and the understanding of invasive species by resolving of taxonomic issues, elucidating geographical sources of invaders, detecting hybridisation and introgression, tracking dispersal and spread and assessing the importance of genetic diversity in invasion success. Finally, we make some suggestions for future research efforts in molecular ecology of biological invasions.     

Assessing the Effect of Sequencing Depth and Sample Size in Population Genetics Inferences

Next-Generation Sequencing (NGS) technologies have dramatically revolutionised research in many fields of genetics. The ability to sequence many individuals from one or multiple populations at a genomic scale has greatly enhanced population genetics studies and made it a data-driven discipline. Recently, researchers have proposed statistical modelling to address genotyping uncertainty associated with NGS data. However, an ongoing debate is whether it is more beneficial to increase the number of sequenced individuals or the per-sample sequencing depth for estimating genetic variation. Through extensive simulations, I assessed the accuracy of estimating nucleotide diversity, detecting polymorphic sites, and predicting population structure under different experimental scenarios. Results show that the greatest accuracy for estimating population genetics parameters is achieved by employing a large sample size, despite single individuals being sequenced at low depth. Under some circumstances, the minimum sequencing depth for obtaining accurate estimates of allele frequencies and to identify polymorphic sites is , where both alleles are more likely to have been sequenced. On the other hand, inferences of population structure are more accurate at very large sample sizes, even with extremely low sequencing depth. This all points to the conclusion that under various experimental scenarios, in cost-limited population genetics studies, large sample sizes at low sequencing depth are desirable to achieve high accuracy. These findings will help researchers design their experimental set-ups and guide further investigation on the effect of protocol design for genetic research.     

Early 20th-century research at the interfaces of genetics, development, and evolution: reflections on progress and dead ends

Three early 20th-century attempts at unifying separate areas of biology, in particular development, genetics, physiology, and evolution, are compared in regard to their success and fruitfulness for further research: Jacques Loeb's reductionist project of unifying approaches by physico-chemical explanations; Richard Goldschmidt's anti-reductionist attempts to unify by integration; and Sewall Wright's combination of reductionist research and vision of hierarchical genetic systems. Loeb's program, demanding that all aspects of biology, including evolution, be studied by the methods of the experimental sciences, proved highly successful and indispensible for higher level investigations, even though evolutionary change and properties of biological systems up to now cannot be fully explained on the molecular level alone. Goldschmidt has been appraised as pioneer of physiological and developmental genetics and of a new evolutionary synthesis which transcended neo-Darwinism. However, this study concludes that his anti-reductionist attempts to integrate genetics, development and evolution have to be regarded as failures or dead ends. His grand speculations were based on the one hand on concepts and experimental systems that were too vague in order to stimulate further research, and on the other on experiments which in their core parts turned out not to be reproducible. In contrast, Sewall Wright, apart from being one of the architects of the neo-Darwinian synthesis of the 1930s, opened up new paths of testable quantitative developmental genetic investigations. He placed his research within a framework of logical reasoning, which resulted in the farsighted speculation that examinations of biological systems should be related to the regulation of hierarchical genetic subsystems, possibly providing a mechanism for development and evolution. I argue that his suggestion of basing the study of systems on clearly defined properties of the components has proved superior to Goldschmidt's approach of studying systems as a whole, and that attempts to integrate different fields at a too early stage may prove futile or worse.     

Towards a cyberinfrastructure for the biological sciences: progress, visions and challenges

Biology is an information-driven science. Large-scale data sets from genomics, physiology, population genetics and imaging are driving research at a dizzying rate. Simultaneously, interdisciplinary collaborations among experimental biologists, theorists, statisticians and computer scientists have become the key to making effective use of these data sets. However, too many biologists have trouble accessing and using these electronic data sets and tools effectively. A 'cyberinfrastructure' is a combination of databases, network protocols and computational services that brings people, information and computational tools together to perform science in this information-driven world. This article reviews the components of a biological cyberinfrastructure, discusses current and pending implementations, and notes the many challenges that lie ahead.     

Genetic and biochemical analysis of development in Toxoplasma gondii.

Toxoplasma gondii has recently come under intense study as a model for intracellular parasitism because it has a number of properties that facilitate experimental manipulation. Attention is now being turned towards understanding the developmental biology of this complex parasite. The differentiation between the two asexual stages, the rapidly growing tachyzoites and the more slowly dividing, encysted bradyzoites, is of particular interest. Progression from the former to the latter is influenced by the host''s immune response. This paper describes current progress on a number of research fronts, all aimed at understanding the triggers that push the tachyzoite-bradyzoite equilibrium in one or other direction and the changes that occur in gene expression (and ultimately metabolism and function). Chief among the techniques used for these studies are genetics and molecular genetics. Recent progress in these areas is described.     

DO RECENT FINDINGS IN PLANT MITOCHONDRIAL MOLECULAR AND POPULATION GENETICS HAVE IMPLICATIONS FOR THE STUDY OF GYNODIOECY AND CYTONUCLEAR CONFLICT?

The coexistence of females and hermaphrodites in plant populations, or gynodioecy, is a puzzle recognized by Darwin. Correns identified cytoplasmic inheritance of one component of sex expression, now known as cytoplasmic male sterility (CMS). Lewis established cytonuclear inheritance of gynodioecy as an example of genetic conflict. Although biologists have since developed an understanding of the mechanisms allowing the joint maintenance of CMS and nuclear male fertility restorer genes, puzzles remain concerning the inheritance of sex expression and mechanisms governing the origination of CMS. Much of the theory of gynodioecy rests on the assumption of maternal inheritance of the mitochondrial genome. Here we review recent studies of the genetics of plant mitochondria, and their implications for the evolution and transmission of CMS. New studies of intragenomic recombination provide a plausible origin for the chimeric ORFs that characterize CMS. Moreover, evidence suggests that nonmaternal inheritance of mitochondria may be more common than once believed. These findings may have consequences for the maintenance of cytonuclear polymorphism, mitochondrial recombination, generation of gynomonoecious phenotypes, and interpretation of experimental crosses. Finally we point out that CMS can alter the nature of the cytonuclear conflict that may have originally selected for uniparental inheritance.     

生物教育专业《遗传学》教学改革的探索

遗传学是生命科学的基础学科, 同时也是生物类专业的必修课。农、林、牧、医、师范、综合类等院校都开设遗传学课程, 由于专业性质及培养目标的不同, 《遗传学》课程在知识体系和内容侧重点等方面都有所区别, 作者就生物教育专业如何优化《遗传学》教学内容及教学方法的改革等方面进行了探索, 提出了见解。     

On the origins of the Mendelian laws

The two laws usually attributed to Mendel were not considered as laws by him. The first law, the law of independent segregation occurs in Mendel's paper as an assumption or hypothesis. Hugo de Vries refers to this as a law discovered by Mendel. This appears to be the first use of an expression equivalent to Mendel's law. In his paper de Vries did not associate the observable characters with structures having a causitive role. That was done by Correns, who transformed the law of segregation of characters into a law of the segregation of anlagen. The second law, the law of independent assortment, is present in embryonic form in Mendel's paper. Here the independent assortment of characters appears as a secondary conclusion to a series of experiments involving several pairs of traits. Mendel repeats the primary conclusion later in the paper but not the secondary one. This leads us to believe that he considered the secondary conclusion as of lesser importance. We note in this context that the 9:3:3:1 ratio commonly associated with the idea of independent assortment, and attributed to Mendel, also does not occur in his paper. A careful reading of the papers of his discoverers shows it was Correns who first drew attention to this ratio. However, he did not formulate the second Mendelian law even though it was clearly implied. Neither was it stated by de Vries. Indeed, the first clear separation of the two laws and the naming of the second law was by T. H. Morgan some 13 years later.     

Beyond race: towards a whole-genome perspective on human populations and genetic variation

The renewed emphasis on population-specific genetic variation, exemplified most prominently by the International HapMap Project, is complicated by a longstanding, uncritical reliance on existing population categories in genetic research. Race and other pre-existing population definitions (ethnicity, religion, language, nationality, culture and so on) tend to be contentious concepts that have polarized discussions about the ethics and science of research into population-specific human genetic variation. By contrast, a broader consideration of the multiple historical sources of genetic variation provides a whole-genome perspective on the ways i n which existing population definitions do, and do not, account for how genetic variation is distributed among individuals. Although genetics will continue to rely on analytical tools that make use of particular population histories, it is important to interpret findings in a broader genomic context.     

Genetics of behavior in the silver fox

The silver fox provides a rich resource for investigating the genetics of behavior, with strains developed by intensely selective breeding that display markedly different behavioral phenotypes. Until recently, however, the tools for conducting molecular genetic investigations in this species were very limited. In this review, the history of development of this resource and the tools to exploit it are described. Although the focus is on the genetics of domestication in the silver fox, there is a broader context. In particular, one expectation of the silver fox research is that it will be synergistic with studies in other species, including humans, to yield a more comprehensive understanding of the molecular mechanisms and evolution of a wider range of social cognitive behaviors.