Advances in Genetics最新文献

Although Darwin's Pangenesis received strong criticism and never gained any very wide acceptance, it was of great importance due to its stimulating effect on later work and thought. Nearly every major theory of heredity developed in the late 19th century began with a discussion of Darwin's Pangenesis. Darwin was shown to play a more important role in the history of genetics than hitherto attributed to him by historians through a detailed analysis of the influence of his Pangenesis on de Vries' "Intracellular Pangenesis" and "The Mutation Theory," Weismann's theory of "Continuity of the Germ-plasm," Galton's "A Theory of Heredity" and "Natural Inheritance," Brooks' "The Law of Heredity, Ross's "Graft Theory of Diseases", Haeckel's perigenesis and Kozo-Polyansky's hypothetical version of symbiogenesis. Without Darwin's Pangenesis they would not have the foundation on which they formulated. By comparing these theories, it may be concluded that Darwin's Pangenesis combines all advantages of its sister-theories, and is more valuable, comprehensive and convincing than any other genetical theories yet advanced.

Although there were many records of graft-induced variations in ancient China, it was Darwin who coined the term "graft hybridization", the formation of hybrids between distinct species or varieties, through plant grafting, without the intervention of the sexual organs. He described many cases of the so-called "graft hybrids", in which shoots produced from grafted plants exhibited a combination of characters of both rootstock and scion, and explained their formation by his Pangenesis. Michurin invented "mentor-grafting" and "preliminary vegetative approximation" methods, which greatly increased the production of graft hybrids, thus providing a solution to Darwin's puzzle. Over the past decides, the existence of graft hybrids has been extensively documented, and graft hybridization is considered to be a simple and efficient means of plant breeding, and would be especially significant in the improvement of fruit trees. Graft hybridization is now explained by horizontal gene transfer and DNA transformation. In addition, the long-distance transport of mRNA and small RNAs is also considered to be involved in the formation of graft hybrids.

Darwin clearly described certain anomalous phenomena, including what he referred to as "the direct action of the male element on the female form" and what we now call xenia and telegony, bud variation (mutation), reversion or atavism, and the inheritance and non-inheritance of mutilation. Some phenomena, particularly xenia, telegony and the inheritance of mutilation, were considered as doubtful phenomena by such authorities as Weismann and Morgan. Over the past 150 year, however, there has been increasing evidence for xenia, which is of great interest and importance in physiological research and plant production. The discoveries of cell-free fetal DNA, sperm RNAs, penetration of sperm into the somatic tissues of the female reproductive tract and the incorporation of exogenous DNA into somatic cells indicate that molecular mechanisms exist for telegony, one of the most controversial issues. Darwin's Pangenesis is the only theory that explains all the different types of phenomena.

Darwin carried out a host of carefully controlled cross- and self-pollination experiments in a wide variety of plants, and made a significant and imperishable contribution to the knowledge of hybridization. He not only clearly described the phenomenon of what he called prepotency and what we now call dominance or Mendelian inheritance, but also explained it by his Pangenesis. Recent discovery of small RNAs acting as dominance modifiers supports his Pangenesis regarding the control of prepotency by gemmules. Historical studies show that there is striking evidence that Mendel read Darwin's The Origin of Species, which had influenced his paper presented in 1865 and published in 1866. Although Mendel's paper has been considered a classic in the history of genetics, it generated much controversy since its rediscovery. Mendel's position as the father of genetics is being seriously challenged. Darwin's main contribution to genetics was the collection of a tremendous amount of genetic data, and the formulation of a comprehensive genetical theory for their explanation. Over the past 150 years, however, Darwin's legacy to genetics, particularly his Pangenesis, has not been considered seriously by most geneticists. It is proposed that Darwin should have been regarded as one of the most important pioneers in genetics.

Darwin's gemmules were supposed to be "thrown off" by cells and were "inconceivably minute and numerous as the stars in heaven." They were capable of self-propagation and diffusion from cell to cell, and circulation through the system. The word "gene" coined by Wilhelm Johannsen, was derived from de Vries's term "pangen," itself a substitute for "gemmule" in Darwin's Pangenesis. Johannsen resisted the "morphological" conception of genes as particles with a certain structure. Morgan's genes were considered to be stable entities arranged in an orderly linear pattern on chromosomes, like beads on a string. In the late 1940s, McClintock challenged the concept of the stability of the gene when she discovered that some genes could move within a chromosome and between chromosomes. In 1948, Mandel and Metais reported the presence of cell-free nucleic acids in human blood for the first time. Over the past several decades, it has been universally accepted that almost all types of cells not only shed molecules such as cell-free DNA (including genomic DNA, tumor DNA and fetal DNA), RNAs (including mRNA and small RNAs) and prions, but also release into the extracellular environment diverse types of membrane vesicles (known as extracellular vesicles) containing DNA, RNA and proteins. Thus Darwin's speculative gemmules of the 19th century have become the experimentally demonstrated circulating cell-free DNA, mobile RNAs, prions and extracellular vesicles.

This chapter briefly discusses Darwin's The Origin of Species and its companion volume The Variation of Animals and Plants under Domestication. It is in the second great book that Darwin took a broad survey of the whole range of variation and heredity, and developed his Pangenesis, an expanded cell theory and a unified genetical theory that would strengthen his theory of evolution and explains the numerous phenomena of life. The essential assumption of Pangenesis is the existence of inherited particles or molecules called gemmules, and their production by cells at each stage of development. He assumed that besides the ordinary cellular division, cells could also "throw off" numerous and minute gemmules, which were capable of self-replication and dormancy, diffusion from cell to cell or circulation through the body, modification by the effects of use and disuse or environmental changes, union with nascent cells, aggregation into buds and germ cells, and transmission from parent to offspring. By his Pangenesis, Darwin not only explained the general phenomena pertaining to inheritance, variation, development and reproduction, but also the inheritance of acquired characters, prepotency, graft hybridization, reversion, regeneration, xenia, telegony, transposition, sex-linked inheritance, the inheritance and non-inheritance of mutilation, and many other facts. Darwin called Pangenesis his "beloved child", and firmly believed that it "will turn out true some day!"

Since the end of the 19th century, Lamarck's name has been tightly linked to the notion of the inheritance of acquired characters. Darwin regarded Lamarck as a great zoologist and a forerunner of evolution, and repeatedly expressed the opinion that "natural selection has been the main but not the exclusive means of modification." The original Darwinism not only includes natural selection, but also the inheritance of acquired characters and mutation. Neo-Darwinism considers natural selection as the one controlling process of evolution, but denies the inheritance of acquired characters. Lysenkoism accepts the inheritance of acquired characters and graft hybridization, but denies the significance of Malthusism and Mutationism. It has been suggested that the "modern synthesis", which evolved from neo-Darwinism, needs a rethink. I propose that there is a need to go back to Darwin's own synthesis which combined his theory of evolution by natural selection with his theory of heredity and variation - Pangenesis.

Since the earliest days of evolutionary thought, the problem of the inheritance of acquired characters has been a central debate. Darwin accepted the inheritance of acquired characters as an established fact and gave many instances. His Pangenesis was more than anything else an attempt to provide a theory for its explanation. Over the past several decades, there has been increasing evidence for the inheritance of acquired habit and immunity, and for heritable changes induced by food and fertilizer, stress, chemicals, temperature, light and other environmental factors. Many studies also suggest that parental age has certain influences on the characters of offspring. The current explanations include environmentally induced DNA changes (mainly DNA rearrangements and DNA methylation), RNA-mediated inheritance, and horizontal gene transfer. These mechanistic explanations are consistent with Darwin's Pangenesis.

Our own species has a diurnal activity pattern and an average circadian period of 24.2h. Exact determination of circadian period requires expensive and intrusive protocols, and investigators are therefore using chronotype questionnaires as a proxy quantitative measure. Both measures show a normal distribution suggestive of a polygenic trait. The genetic components of the 24-h feedback loop that generates circadian rhythms within our cells have been mapped in detail, identifying a number of candidate genes which have been investigated for genetic polymorphisms relating to the phenotypic variance. Key in this mechanism is the inhibitory complex containing period and cryptochrome proteins and interacting protein kinases and ubiquitin ligases, and the stability of this complex is recognized as the major determinant of circadian periodicity. The identification of the causative mutations in familial circadian rhythms sleep disorders has shed additional light into this mechanism. Mutations in the negative feedback protein-encoding genes PER2 and CRY2 as well as the CSNK1D gene encoding casein kinase I delta have been shown to cause advanced sleep phase disorder, and a mutation in the CRY1 gene delayed sleep phase disorder. The candidate gene approach has also yielded a number of genetic associations with chronotype as determined by questionnaires. More recently, genome-wide association studies of chronotype have both confirmed associations with the candidate clock gene PER2 and identified a serious of novel genes associated with variability in circadian rhythmicity, which have yet to be explored. While considerable progress has thus been made with mapping the phenotypic diversity in human circadian rhythms and the genomic variability that causes it, studies to date have been mostly focused on individuals of European descent, and there is a strong need for research on other populations.

The filamentous fungus Neurospora crassa possesses a process called meiotic silencing by unpaired DNA (MSUD). MSUD has a remarkable ability to scan homologous chromosomes for unpaired DNA during meiosis. After unpaired DNA is identified, MSUD silences all RNA from the unpaired DNA along with any RNA transcribed from homologous sequences at other locations in the genome, regardless of their pairing state. The mechanism by which unpaired DNA is detected is unknown. Unpaired DNA segments can be as short as 1.3kb, if not shorter, and DNA sequences with only a small level of polymorphism (6%) can be considered unpaired by MSUD. MSUD research has identified nine proteins required for full efficiency of the process, three of which are homologs of the canonical RNA interference (RNAi) proteins Dicer, Argonaute, and RNA-dependent RNA polymerase. Most MSUD proteins, including the RNAi homologs, appear to dock outside of the nuclear envelope during early stages of meiosis. Only two have been observed inside the nucleus, a low number given that the identification of unpaired DNA and the triggering of silencing must begin within this location. These two proteins may participate in the unpaired DNA detection process. Recent evidence indicates that the search for unpaired DNA is spatially constrained, possibly because of restrictions on the arrangement of chromatin loops during or after homolog pairing. This review attempts to provide a complete analysis of past, present, and future directions of MSUD research, starting with its discovery during a search for a conserved regulator of fungal development and ending with some benefits the process may provide to MSUD capable organisms.