Richard Goldschmidt: hopeful monsters and other 'heresies'

Richard Goldschmidt is remembered today as one of the most controversial biologists of the twentieth century. Although his work on sex determination and physiological genetics earned him accolades from his peers, his rejection of the classical gene and his unpopular theories about evolution significantly damaged his scientific reputation. This article reviews Goldschmidt's life and work, with an emphasis on his controversial views.     

Of moths and men: Theo Lang and the persistence of Richard Goldschmidt's theory of homosexuality, 1916-1960

Using an analogy between moths and men, in 1916, Richard Goldschmidt proposed that homosexuality was a case of genetic intersexuality. As he strove to create a unified theory of sex determination that would encompass animals ranging from moths to men, Goldschmidt's doubts grew concerning the association of homosexuality with intersexuality until, in 1931, he dropped homosexuality from his theory of intersexuality. Despite Goldschmidt's explicit rejection of his theory of homosexuality, Theo Lang, a researcher in the Genealogical-Demographic Department of the Institute for Psychiatric Research in Munich, revived it, maintained Goldschmidt's association with it, and argued on its behalf in publications from 1936 to 1960. Lang's appropriation of Goldschmidt's theory did not depend on his resolution of the difficulties Goldschmidt had found with his own theory. Lang and Goldschmidt, I argue, had fundamentally different scientific and social commitments that allowed one to reject this theory of homosexuality and the other to accept it.     

R. Goldschmidt and J. Huxley: creative parallelisms

The comparative analysis of scientific heritage of Richard Goldschmidt and Julian Huxley shows convincingly the resemblance of these two scientists' views over the core problems of evolutionary theory, genetics and development biology. They both contributed to developing a triad "genetics--development--evolution". The problem of a relative growth of animals was the central point in both Goldschmidt's and Huxley's works. Huxley developed a formula of the allometric growth (law of constant differential growth) while Goldschmidt was the first to draw up the broad interpretation of the consequences of that phenomenon. Both scientists belonged to initiators of development genetics and used the "non-morganian" genetics in their efforts of solving problems of macroevolution. Goldschmidt tended toward an idea of an important role of macromutation in the process of macroevolution, though Huxley adhered to more moderate views. But at the same time the concept of preadaptive mutations proposed by Huxley was close to Goldschmidt's idea of macromutants. It is shown that both scientists analyzed profoundly the changes in early stages of embryogenesis in respect to macroevolution. It is not likely to be reasonable to oppose firmly Goldschmidt's saltationism to the evolutionary synthesis of Huxley. They developed the larger biological problems in a similar way, and undoubtedly their works in the field helped to enrich the development of the views over genetics and evolution. The open-minded analysis of Goldschmidt's and Huxley's concepts leads to creating modern and up-to-date views over the theory of evolution where seemingly incompatible things go together rather well and supplement each other. Evo-Devo rediscovered Goldshmidt's Biology and Huxley's Synthesis.     

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.     

Macromutation and evolution: the fixation of Goldschmidt's macromutations as species and genus traits. Hairlessness mutations in mammals

A brief survey of the development of concepts on the role of macromutations in evolution is given. Contrary to Iu. A. Filipchenko (1926, 1927), who introduced the "micro- and macromutation" terms and believed that regularities of macroevolution could not be reduced to microevolutionary processes, the majority of "synthetists" explained any form of evolution by changes in allele frequencies. From the studies of Drosophila homoeotic mutants R. Goldschmidt (1940) developed the concept of "hopeful monsters" and their role in macroevolution. However, the homoeotic mutants are of drastically reduced viability, which allows the gradualists to reject Goldschmidt's ideas. The distribution of hairlessness mutations (hairless, nude etc.) with the monogenic pattern of inheritance in mammals was studied. Hairless mutants are known in Peromyscus, Mus musculus, Rattus rattus, R. norvegicus, Canis familiaris, Ovis aries. Hairlessness as norm is found in 53 among contemporaneous 1037 mammalian genera. Part of these cases (hairlessness in all Cetacea and Sirenia) may be explained in terms of both macromutations and obligatory gradualism. There is no doubt as to the macromutational origin of hairlessness in the bat Cheiromeles and the rodent Heterocephalus (Bathyergidae); the genera systematically and ecologically close to these have normal pelage. It is quite possible that hairlessness of walrus (Odobenus) has the same origin. The appearance and fixation of single Goldschmidt's macromutation cannot yet be considered as a macroevolutionary process, though the possibility of fixation of a macromutation in nature as a species and genus character contradicts strongly the concept of obligatory gradualism of evolution.     

Epigenetics and the renaissance of heresy.

Classic neo-Darwinian theory is predicated on the notion that all heritable phenotypic change is mediated by alterations of the DNA sequence in genomes. However, evidence is accumulating that stably heritable phenotypes can also have an epigenetic basis, lending support to the long-discarded notion of inheritance of acquired traits. As many of the examples of epigenetic inheritance are mediated by position effects, the possibility exists that chromosome rearrangements may be one of the driving forces behind evolutionary change by exerting position effect alterations in gene activity, an idea articulated by Richard Goldschmidt. The emerging evidence suggests that Goldschmidt's controversial hypothesis deserves a serious reevaluation.     

花器官发育的分子机制研究进展

经典的ABC模型成功地解释了模式植物拟南芥和金鱼草因同源异型基因突变而引起的植物花器官的变异。随后,大量花器官特征基因和新突变体的研究不断完善和发展了ABC模型。该文综述了近年来花器官发育分子模型及花器官同源基因的调控机理等方面的最新研究成果,并对未来的研究方向进行了展望,以期为深入了解花发育的分子机理和遗传机制奠定基础。     

Sex determination in the monoecious species cucumber is confined to specific floral whorls

In unisexual flowers, sex is determined by the selective repression of growth or the abortion of either male or female reproductive organs. The mechanism by which this process is controlled in plants is still poorly understood. Because it is known that the identity of reproductive organs in plants is controlled by homeotic genes belonging to the MADS box gene family, we analyzed floral homeotic mutants from cucumber, a species that bears both male and female flowers on the same individual. To study the characteristics of sex determination in more detail, we produced mutants similar to class A and C homeotic mutants from well-characterized hermaphrodite species such as Arabidopsis by ectopically expressing and suppressing the cucumber gene CUCUMBER MADS1 (CUM1). The cucumber mutant green petals (gp) corresponds to the previously characterized B mutants from several species and appeared to be caused by a deletion of 15 amino acid residues in the coding region of the class B MADS box gene CUM26. These homeotic mutants reveal two important concepts that govern sex determination in cucumber. First, the arrest of either male or female organ development is dependent on their positions in the flower and is not associated with their sexual identity. Second, the data presented here strongly suggest that the class C homeotic function is required for the position-dependent arrest of reproductive organs.     

Reinventing Richard Goldschmidt: Reputation,Memory, and Biography

Richard Goldschmidt was one of the most controversial biologists of the mid-twentieth century. Rather than fade from view, Goldschmidt’s work and reputation has persisted in the biological community long after he has. Goldschmidt’s longevity is due in large part to how he was represented by Stephen J. Gould. When viewed from the perspective of the biographer, Gould’s revival of Goldschmidt as an evolutionary heretic in the 1970s and 1980s represents a selective reinvention of Goldschmidt that provides a contrast to other kinds of biographical commemorations by scientists.     

Homeotic duplication of the pelvic body segment in regenerating tadpole tails induced by retinoic acid

 Homeosis, the ectopic formation of a body part, is one of the key phenomena that prompted the identification of the essential selector genes controlling body organization. Shared elements of such homeotic genes exist in all studied animal classes, but homeotic transformations of the same order of magnitude as in insects, such as the duplication of the thorax in Drosophila mutants, have not been described in vertebrates. Here we investigate the capacity of retinoic acid to modify tail regeneration in amphibians. We show that retinoic acid causes the formation of an additional body segment in regenerating tails of Rana temporaria tadpoles. A second pelvic section, including vertebral elements, pelvic girdle elements and limb buds, forms at the mid-tail level. This is the first report of a homeotic duplication of a whole body segment in vertebrate axial regeneration. Received: 16 August 1996 / Accepted: 20 September 1996     

Identification of Homeotic Target Genes in Drosophila Melanogaster Including Nervy, a Proto-Oncogene Homologue

In Drosophila, the specific morphological characteristics of each segment are determined by the homeotic genes that regulate the expression of downstream target genes. We used a subtractive hybridization procedure to isolate activated target genes of the homeotic gene Ultrabithorax (Ubx). In addition, we constructed a set of mutant genotypes that measures the regulatory contribution of individual homeotic genes to a complex target gene expression pattern. Using these mutants, we demonstrate that homeotic genes can regulate target gene expression at the start of gastrulation, suggesting a previously unknown role for the homeotic genes at this early stage. We also show that, in abdominal segments, the levels of expression for two target genes increase in response to high levels of Ubx, demonstrating that the normal down-regulation of Ubx in these segments is functional. Finally, the DNA sequence of cDNAs for one of these genes predicts a protein that is similar to a human proto-oncogene involved in acute myeloid leukemias. These results illustrate potentially general rules about the homeotic control of target gene expression and suggest that subtractive hybridization can be used to isolate interesting homeotic target genes.     

Extreme divergence of a homeotic gene: the bicoid case

Evolutionary developmental genetics (evo-devo) reveals that the plasticity of development is so important that every developmental biology project should carefully take this point into consideration. The example of bicoid, the first discovered morphogen, illustrates how an essential gene can change its function during evolution. The search for bicoid homologues showed that this gene is surprisingly specific to flies (cyclorraphan diptera) and absent in other insects. In fact, recent studies demonstrate that bicoid is a very derived Hox3 homeotic gene. During insect evolution, the ancestral Hox3 gene lost its homeotic function and acquired new roles in oocytes and embryonic annexes. Then, in the lineage leading to modern flies, a duplication of this new gene, followed by functional divergence, led to the formation of bicoid and zerknüllt. Both genes are located within the Drosophila Hox complex; however, they have no homeotic function. Thanks to the power of Drosophila genetics, it is possible to suggest that torso and hunchback may constitute the insect primitive anterior organizer. The bicoid evolutionary history reveals several fundamental mechanisms of the evolution of developmental genes, such as changes of gene regulation, modifications of protein sequences and gene duplication. It also shows the need for studying a wider range of model organisms before generalisations can be made from data obtained with one particular species.     

利用荧光标记高通量鉴定减数分裂重组抑制突变体

正向遗传学突变体筛选被广泛用于揭示减数分裂中涉及的遗传基因, 如调控减数分裂II型交叉形成途径的重组抑制基因。该研究利用拟南芥(Arabidopsis thaliana)花粉荧光标记系进行EMS突变体的正向遗传学筛选, 鉴定拟南芥野生型Col遗传背景下的重组抑制突变体, 共获得18个重组率显著提高3倍以上的重组抑制突变体, 其中包括显性和隐性遗传突变。研究表明, 基于荧光标记高通量鉴定重组抑制突变体是可行的, 可为植物减数分裂重组调控分子机制研究提供新方法和突变材料。     

The identification of candidate genes for a reverse genetic analysis of development and function in the Arabidopsis gynoecium

The screening for mutants and their subsequent molecular analysis has permitted the identification of a number of genes of Arabidopsis involved in the development and functions of the gynoecium. However, these processes remain far from completely understood. It is clear that in many cases, genetic redundancy and other factors can limit the efficiency of classical mutant screening. We have taken the alternative approach of a reverse genetic analysis of gene function in the Arabidopsis gynoecium. A high-throughput fluorescent differential display screen performed between two Arabidopsis floral homeotic mutants has permitted the identification of a number of genes that are specifically or preferentially expressed in the gynoecium. Here, we present the results of this screen and a detailed characterization of the expression profiles of the genes identified. Our expression analysis makes novel use of several Arabidopsis floral homeotic mutants to provide floral organ-specific gene expression profiles. The results of these studies permit the efficient targeting of effort into a functional analysis of gynoecium-expressed genes.     

利用荧光标记高通量鉴定减数分裂重组抑制突变体

正向遗传学突变体筛选被广泛用于揭示减数分裂中涉及的遗传基因, 如调控减数分裂II型交叉形成途径的重组抑制基因。该研究利用拟南芥(Arabidopsis thaliana)花粉荧光标记系进行EMS突变体的正向遗传学筛选, 鉴定拟南芥野生型Col遗传背景下的重组抑制突变体, 共获得18个重组率显著提高3倍以上的重组抑制突变体, 其中包括显性和隐性遗传突变。研究表明, 基于荧光标记高通量鉴定重组抑制突变体是可行的, 可为植物减数分裂重组调控分子机制研究提供新方法和突变材料。     

A brief history of regeneration research—For admiring Professor Niazi’s discovery of the effect of vitamin A on regeneration

Studies of regeneration research has a very profound historical background, longer than genetics and embryologyper se. In this article, I have tried to make clear the importance of the discovery of Niazi on the effect of vitamin A on amphibian limb regeneration in the long tradition of regeneration study. His discovery is truly one of the main milestones in recent era of the field. It revitalized the study of regeneration, in particular the problem of replication of pattern. A more recent discovery of heteromorphic regeneration in tadpoles elicited by vitamin A by Mohanty-Hejmadi is also of a great historical significance. It has opened the way to investigate the most mysterious phenomena known from early 20th in modern eyes, most probably in terms of the epigenetic switch of homeotic genes     

花器官决定的ABC模型和四因子模型

简要介绍了花器官决定的同源异型基因作用模型--ABC模型的产生和发展过程.从早期ABC模型发展到经典ABC模型,然后到ABCD模型,最后到A-E模型.花器官发育遗传学的创立和发展是ABC模型产生的基础,ABC模型的建立促进了花器官发育遗传学的发展,而后者进一步发展的结果又促使前者更加完善,从而进一步发展为四因子模型.