Self-Organization of the Biological Evolution.

We report here experiments carried out with nonpathogenic Escherichia coli bacterial strains and their phages. This research yielded interesting insights into their activities, occasionally producing genetic variants of different types. In order to not interfere with the genetic stability of the parental strains involved, we found that the bacteria are genetically equipped to only rarely produce a genetic variant, which may occur by a number of different approaches. On the one hand, the genes of relevance for the production of specific genetic variants are relatively rarely expressed. On the other hand, other gene products act as moderators of the frequencies that produce genetic variants. We call the genes producing genetic variants and those moderating the frequencies of genetic variation "evolution genes". Their products are generally not required for daily bacterial life. We can, therefore, conclude that the bacterial genome has a duality. Some of the bacterial enzymes involved in biological evolution have become useful tools (e.g., restriction endonucleases) for molecular genetic research involving the genetic set-up of any living organism.

Horizontal Gene Transfer among Bacteria and Its Role in Biological Evolution.

This is a contribution to the history of scientific advance in the past 70 years concerning the identification of genetic information, its molecular structure, the identification of its functions and the molecular mechanisms of its evolution. Particular attention is thereby given to horizontal gene transfer among microorganisms, as well as to biosafety considerations with regard to beneficial applications of acquired scientific knowledge.

Molecular Darwinism: the contingency of spontaneous genetic variation.

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions.

Genetic engineering compared to natural genetic variations.

By comparing strategies of genetic alterations introduced in genetic engineering with spontaneously occurring genetic variation, we have come to conclude that both processes depend on several distinct and specific molecular mechanisms. These mechanisms can be attributed, with regard to their evolutionary impact, to three different strategies of genetic variation. These are local nucleotide sequence changes, intragenomic rearrangement of DNA segments and the acquisition of a foreign DNA segment by horizontal gene transfer. Both the strategies followed in genetic engineering and the amounts of DNA sequences thereby involved are identical to, or at least very comparable with, those involved in natural genetic variation. Therefore, conjectural risks of genetic engineering must be of the same order as those for natural biological evolution and for conventional breeding methods. These risks are known to be quite low. There is no scientific reason to assume special long-term risks for GM crops. For future agricultural developments, a road map is designed that can be expected to lead, by a combination of genetic engineering and conventional plant breeding, to crops that can insure food security and eliminate malnutrition and hunger for the entire human population on our planet. Public-private partnerships should be formed with the mission to reach the set goals in the coming decades.

The 2009 Lindau Nobel Laureate Meeting: Werner Arber, physiology or medicine 1978.

Swiss microbial geneticist, Werner Arber shared the 1978 Nobel Prize in Physiology or Medicine with Hamilton Smith and Daniel Nathans for their discovery of restriction endonucleases. Werner Arber was born in Granichen, Switzerland in 1929. Following a public school education, he entered the Swiss Polytechnical School in Zurich in 1949, working toward a diploma in natural sciences. There, his first research experience involved isolating and characterizing an isomer of chlorine. Following graduation in 1953, Arber joined a graduate program at the University of Geneva, taking on an assistanceship in electron microscopy (EM), in which he studied gene transfer in the bacterial virus (bacteriophage) lambda. Eventually encountering limitations with EM as a tool, he began using microbial genetics as a methodology for his studies. The study of microbial genetics had been possible for a relatively short time: DNA had been discovered to carry genetic information only a decade before he d entered the field. After earning his Ph.D. in 1958, Arber continued to develop skills in microbial genetics, working with colleagues in the United States for a short time before returning to Geneva at beginning of 1960. There, he continued working on lambda transduction in E. coli, but found that the virus would not efficiently propagate. Recalling research done seven years earlier by Joe Bertani and Jean Weigle on "host-controlled restriction-modification", he realized there must be a host-controlled modification of the invading DNA, and sought to identify the mechanism. Based on Grete Kallengerger s work that demonstrated degradation of both irradiated and non-irradiated phage lambda following injection in a host, Arber and his graduate student, Daisy Dussoix further investigated the fate of DNA, and found that restriction and modification (later determined to be postreplicative nuclotide methylation) directly affected DNA, but did not cause mutations. They also found that theses were properties of the bacterial strains, and that both viral and cellular DNA were degraded. Together, Arber and Dussoix reported their findings to scientific community in 1961 at the First International Biophysics Congress in Stockholm. Aber also presented the research to the Science Faculty of University of Geneva in 1962, earning the Plantamour-Prevost prize. Based on his work and the work of others, he hypothesized that an enzyme in the host bacterium cut DNA into smaller pieces at specific sites, and methylase modified the host DNA to protect it from the digestive enzyme. These theories were later confirmed by Urs Kuhnlein, who found that mutation of specific sites rendered the phage resistant to cleavage; Hamilton smith, who identified Type II endonuclease HindII; and Daniel Nathans, who used HindII to break the SV40 virus into 11 fragments, allowing him to determine its method of replication. Since the discovery of restriction endonucleases, researchers have used them as tools to study the functions of genes of all types of organisms. Restriction enzymes have also facilitated the study of gene functions and enabled production of substances of medical and nutritional importance. Arber feels that in the next few decades we will learn much from the study of epigentics --factors that can affect the phenotype of an organism without changing the genetic information--. He is proud that, in that studying restriction degradation and DNA methylation in the 1960s, he was among the first in studying epigenetic phenomenon.

Systemic aspects of biological evolution.

In recent years molecular mechanisms and natural strategies have been explored that spontaneously generate genetic variations at low rates without seriously affecting genetic stability at the level of populations. Thereby acquired knowledge suggests systemic aspects of evolutionary interdependences both in the past and in future evolutionary developments. The natural strategy of DNA acquisition by horizontal gene transfer interconnects different branches of the tree of evolution at random times. This makes in principle the entire global gene pool of the biosphere available to any kinds of living beings for their further evolutionary development. The relevance of this knowledge for risk assessments of genetically engineered organisms is discussed.

The impact of science and technology on the civilization.

The rapid increase of available scientific knowledge is largely due to the introduction of novel research strategies. The application of these strategies, both in fundamental and in translational scientific research, leads to bursts of technological innovations. In order to fulfill the justified public request for sustainability of technological innovations that contribute to the shaping of the future, increasing attention should be given to science-based technology and policy assessment. These requests are illustrated by benefit/risk evaluations of relevance for the use of genetic engineering as an efficient and effective research strategy. Expected benefits of a responsibly planned introduction of GM crops are outlined as a prospective example for the guiding theme "Biotechnology for sustainability of human society".

Genetically encoded generators of genetic variants.

Several specific molecular mechanisms contribute to the generation of genetic variants at low rates. Some of these mechanisms involve the action of specific gene products as variation generators. We discuss here known as well as still hypothetical ways by which natural reality may succeed to keep the rates of genetic variation at low levels that insure a relatively high genetic stability of the individual organisms.

The evolutionary strategy of DNA acquisition as a possible reason for a universal genetic code.

The evolutionary strategy to generate genetic variants by DNA acquisition involving horizontal gene transfer seems to be widely used by many, if not all, living organisms. A common language between donor and recipient organisms, as provided by the quasi universality of the genetic code, can favor the effectiveness of the DNA acquisition strategy. These considerations are here discussed in the context of our knowledge on the natural strategies of molecular evolution and on the commonly used genetic code.

Dual nature of the genome: genes for the individual life and genes for the evolutionary progress of the population.

Biological evolution is here postulated to be driven coordinately by the products of specific evolution genes and by non-genetic elements such as the intrinsic properties of matter and random encounter with environmental factors. Evolution genes are supposed to have their own evolutionary history in which second-order selection was exerted at the population level. The products of evolution genes can act as generators of genetic variations and/or as modulators of the frequency of genetic variation. Three major natural strategies, each with a number of specific mechanisms contribute to the overall spontaneous production of genetic variants. Each of these three strategies contributes its own specific quality to genetic variation. The difficulties of experimentally investigating these strategies and a wider discussion of some of the postulates within the scientific community are outlined. Finally, the general relevance of the postulated duality of the genome for our world view is briefly mentioned.

Gene products with evolutionary functions.

It is often tacitly assumed that all gene products serve the needs of life functions of the individual carrying the genome. However, a close look at the formation of genetic variations, which are the drivers of biological evolution, reveals a different view. While a majority of the products of genes, such as housekeeping genes and genes essential for each individual, when exposed to particular life conditions respond to the definition given above, other gene products clearly carry out evolutionary functions at the level of populations. Products of these evolution genes act as generators of genetic variations and/or as modulators of the frequency of genetic variation. This is most readily seen with bacterial populations. Many different mechanisms contribute to the occasional, overall formation of genetic variations. These mechanisms can be grouped into three mechanistically and qualitatively different strategies of generating genetic variations. In addition to the activities of evolution genes, specific properties of matter such as tautomery also contribute to the formation of genetic variations. The views that nature cares actively for biological evolution are documented by evidence taken mainly from microbial genetics. Essential elements of the theory of molecular evolution are discussed, as well as the relevance of this theory for higher organisms and its impact on our worldview.

Elements for a theory of molecular evolution.

Biological evolution is known to be driven by the availability of genetic variants. Spontaneous genetic variation can be the result of a number of specific molecular mechanisms. These can be grouped into three qualitatively different natural strategies of generating genetic variations, namely local sequence changes, DNA rearrangement within the genome and horizontal gene transfer, which is referred to here as DNA acquisition. All of these strategies bring about alterations in the DNA sequences of the genome, thus corresponding to the molecular genetic definition of the term mutation. A detailed inspection of specific mechanisms of mutagenesis reveals on the one hand the impact of non-genetic internal and environmental factors, and on the other hand the specific involvement of gene products. The underlying so-called evolution genes can be classified into generators of genetic variations and into modulators of the frequency of genetic variation. These evolution genes are postulated to have themselves undergone biological evolution under the pressure of second-order selection. On the basis of a few selected examples of mutagenesis, elements for a theory of molecular evolution are collected without a claim for completeness. Philosophical dimensions as well as practical aspects of the advanced knowledge on specific molecular mechanisms involved in molecular evolution are also briefly discussed.