Structure and evolution of the genetic code viewed from the perspective of the experimentally expanded amino acid repertoire in vivo

Much effort has been devoted recently to expanding the amino acid repertoire in protein biosynthesis in vivo. From such experimental work it has emerged that some of the non-canonical amino acids are accepted by the cellular translational machinery while others are not, i.e. we have learned that some determinants must exist and that they can even be anticipated. Here, we propose a conceptual framework by which it should be possible to assess deeper levels of the structure of the genetic code, and based on this experiment to understand its evolution and establishment. First, we propose a standardised repertoire of 20 amino acids as a basic set of conserved building blocks in protein biosynthesis in living cells to be the main criteria for genetic code structure and evolutionary considerations. Second, based on such argumentation, we postulate the structure and evolution of the genetic code in the form of three general statements: (i) the nature of the genetic code is deterministic; (ii) the genetic code is conserved and universal; (iii) the genetic code is the oldest known level of complexity in the evolution of living organisms that is accessible to our direct observation and experimental manipulations. Such statements are discussed as our working hypotheses that are experimentally tested by recent findings in the field of expanded amino acid repertoire in vivo. Received 30 June 1999; accepted 9 July 1999     

Inter- and intrapopulation studies of ancient humans

For a genetic analysis of ancient human populations to be useful, it must be demonstrated that the DNA samples under investigation represent a single human population. Toward that end, we have analyzed human DNA from the Windover site (7000–8000 BP). MHC-I analysis, using allele-specific oligonucleotide hybridization to PCR amplified Windover DNA, microsatellite analysis by PCR of the APO-A2 repeat and mtD-loop 3 region sequencing on multiple individuals spanning nearly the full range of estimated burial dates all confirm the hypothesis that there is a persistence of both nuclear and mitochondrial haplotypes at Windover throughout its entire period of use. Thus, Windover can be considered a single population. Neighbor-joining tree analysis of mtDNA sequences suggests that some mitochondrial types are clearly related to extant Amerind types, whereas others, more distantly related, may reflect genetically distinct origins. A more complete sequence analysis will be required to firmly resolve this issue. Calibrating genetic relationships deduced by tree analysis, radiocarbon dates and burial position, yields a human mtD-loop DNA rate of evolution of 3700 to 14,000 years per percent change. Both values are within the range of recent, independently calculated values using estimates of evolutionary divergence or theoretical population genetics. Thus we are beginning to relaize the promise of ancient DNA analysis to experimentally answer heretofore unapproachable questions regarding human prehistory and genetic change.     

Quantitative genetics of zooplankton life histories

Quantitative genetic techniques are powerful tools for use in understanding the microevolutionary process. Because of their size, lifespan, and ease of culture, many zooplankton species are ideal for quantitative genetic approaches. As model systems, studies of zooplankton life histories are becoming increasingly used for examination of the central paradigms of evolutionary theory. Two of the fundamental empirical questions that zooplankton quantitative genetics studies can answer are: 1) How much genetic variance exists in natural populations for life history traits? 2) What is the empirical evidence for trade-offs that permeate life history theory based on optimality approaches? A review of existing data onDaphnia indicates substantial genetic variance for body size, clutch size, and age at first reproduction. Average broad-sense heritabilities for these three characters across 19 populations of 6 species are 0.31, 0.31, and 0.34, respectively. Although there is some discrepancy between the two pertinent studies that were designed to decompose the total genetic variance into its additive and non-additive components, a crude average seems to suggest that approximately 60% of the total genetic variance has an additive basis. The existing data are somewhat inconsistent with respect to presence/absence of trade-offs (negative genetic correlations) among life history traits. A composite of the existing data seems to argue against the existence of strong trade-offs between offspring size and offspring number, between present and future reproduction, and between developmental rate and fecundity. However, there is some evidence for a shift toward more negative (less positive) covariances in more stressful environments (e.g., low food). Zooplankton will prove to be very useful in future study in several important areas of research, including the genetics and physiology of aging, the importance of genotype-environment interaction for life history traits, and the evolution of phenotypic plasticity.     

Genetics on the neurodiversity spectrum: Genetic,phenotypic and endophenotypic continua in autism and ADHD

How we ought to diagnose, categorise and respond to spectrum disabilities such as autism and Attention Deficit/Hyperactivity Disorder (ADHD) is a topic of lively debate. The heterogeneity associated with ADHD and autism is described as falling on various continua of behavioural, neural, and genetic difference. These continua are varyingly described either as extending into the general population, or as being continua within a given disorder demarcation. Moreover, the interrelationships of these continua are likewise often vague and subject to diverse interpretations.In this paper, I explore geneticists' and self-advocates’ perspectives concerning autism and ADHD as continua. These diagnoses are overwhelmingly analysed as falling on a continuum or continua of underlying traits, which supports the notion of “the neurodiversity spectrum”, i.e., a broader swath of human neural and behavioural diversity on which some concentrations of different functioning are diagnosed. I offer a taxonomy of conceptions of the genetic, phenotypic, and endophenotypic dimensionality within and beyond these diagnostic categories, and suggest that the spectrum of neurodiversity is characteristically endophenotypic.     

重庆地区汉族群体19个STR基因座遗传多态性的研究

采用GoldeneyeTM20A试剂盒复合扩增180例重庆地区无血缘关系汉族个体的19个STR基因座。扩增产物经ABl3130序列分析仪进行检测，GeneMapperIDV3．2．1基因分析软件进行基因分析，得到基因分型图。总共检测出182个等位基因，其频率分布介于0．0028～0．4972。19个STR基因座的杂合度介于0．6611～0．9111，个体识别率介于O．8114～0．9882，匹配概率介于0．0118～0．1886，多态信息含量介于0．6309～0．9190，累积个人识别率和累积多态信息含量均大于0．9999999999，累积匹配概率为3．7189×10-^24“，累积非父排除率为0．9999999964。说明该19个STR基因座具有比较高的多态性，是较理想的遗传标记，所得到的等位基因频率等数据可为重庆地区汉族人群的法医学个人识别、亲子鉴定及群体遗传学等研究提供基础数据。     

Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

Insects mostly develop on decaying and contaminated organic matter and often serve as vectors of biologically transmitted diseases by transporting microorganisms to the plant and animal hosts. As such, insects are constantly ingesting microorganisms, a small fraction of which reach their epithelial surfaces, mainly their digestive tract, where they can establish relationships ranging from symbiosis to mutualism or even parasitism. Understanding the tight physical, genetic, and biochemical interactions that takes place between intestinal epithelia and either resident or infectious microbes has been a long-lasting objective of the immunologist. Research in this field has recently been re-vitalized with the development of deep sequencing techniques, which allow qualitative and quantitative characterization of gut microbiota. Interestingly, the recent identification of regenerative stem cells in the Drosophila gut together with the initial characterization of Drosophila gut microbiota have opened up new avenues of study aimed at understanding the mechanisms that regulate the dialog between the Drosophila gut epithelium and its microbiota of this insect model. The fact that some of the responses are conserved across species combined with the power of Drosophila genetics could make this organism model a useful tool to further elucidate some aspects of the interaction occurring between the microbiota and the human gut.     

Heterozygous effects on cell yield and generation time inSaccharomyces cerevisiae

Summary The data obtained analyzing generation time, cell yield and their variability in different culture media in diploid strains ofSaccharomyces cerevisiae demonstrate the existence of a biochemically determined heterotic effect, that could be of some relevance for the study of yeast population genetics, as well as for the improvement of microbial fermentation processes.     

Asexual reproduction: Genetics and evolutionary aspects

Reproduction is essential to all organisms if they are to contribute to the next generation. There are various means and ways of achieving this goal. This review focuses on the role of asexual reproduction for eukaryotic organisms and how its integration in a life cycle can influence their population genetics and evolution. An important question for evolutionary biologists as to why some organisms reproduce sexually, as opposed to asexually, is addressed. We also discuss the economic and medical importance of asexual organisms. Received 4 December 2006; received after revision 25 January 2007; accepted 20 February 2007     

Neuroimaging, nutrition, and iron-related genes

Several dietary factors and their genetic modifiers play a role in neurological disease and affect the human brain. The structural and functional integrity of the living brain can be assessed using neuroimaging, enabling large-scale epidemiological studies to identify factors that help or harm the brain. Iron is one nutritional factor that comes entirely from our diet, and its storage and transport in the body are under strong genetic control. In this review, we discuss how neuroimaging can help to identify associations between brain integrity, genetic variations, and dietary factors such as iron. We also review iron’s essential role in cognition, and we note some challenges and confounds involved in interpreting links between diet and brain health. Finally, we outline some recent discoveries regarding the genetics of iron and its effects on the brain, suggesting the promise of neuroimaging in revealing how dietary factors affect the brain.     

Population genetics of a colonizing lizard: Loss of variability in introduced populations ofPodarcis sicula

Allozyme electrophoresis was used to study the genetic variability (proportion of polymorphic loci and heterozygosity) in insular populations (Corsica, Elba, Montecristo, Marettimo, Pantelleria) of the lacertid lizardPodarcis sicula. These populations were presumed to have originated from episodes of accidental anthropogenic introduction. In order to test the hypothesis of a man-aided colonization and to provide comparative data, heterozygosity and polymorphism were also estimated in autochthonous populations ofP. sicula from the Italian peninsula and Sicily. In each case, the presumed introduced population showed levels of genetic variability significantly lower than those detected in the autochthonous ones. Very little genetic differentiation was found among native and presumed colonist populations, Nei's standard genetic distances ranging from 0.001 to 0.009. These results strongly support the hypothesis thatP. sicula was only recently introduced to the studied islands, and provide additional evidence of reduced genetic variability due to founder effect in insular populations originating from episodes of human transportation.     

Theories that narrate the world: Ronald A. Fisher's mass selection and Sewall Wright's shifting balance

Theories are composed of multiple interacting components. I argue that some theories have narratives as essential components, and that narratives function as integrative devices of the mathematical components of theories. Narratives represent complex processes unfolding in time as a sequence of stages, and hold the mathematical elements together as pieces in the investigation of a given process. I present two case studies from population genetics: R. A. Fisher's “mas selection” theory, and Sewall Wright's shifting balance theory. I apply my analysis to an early episode of the “R. A. Fisher – Sewall Wright controversy.”     

Selectable genetic markers for nematode transgenesis

The nematode Caenorhabditis elegans has been used to study genetics and development since the mid-1970s. Over the years, the arsenal of techniques employed in this field has grown steadily in parallel with the number of researchers using this model. Since the introduction of C. elegans transgenesis, nearly 20 years ago, this system has been extensively used in areas such as rescue experiments, gene expression studies, and protein localization. The completion of the C. elegans genome sequence paved the way for genome-wide studies requiring higher throughput and improved scalability than provided by traditional genetic markers. The development of antibiotic selection systems for nematode transgenesis addresses these requirements and opens the possibility to apply transgenesis to investigate biological functions in other nematode species for which no genetic markers had been developed to date.     

遗传算法与最小元素法相结合在物流中心选址中的应用

针对单一品种货物的物流中心的选址问题，采用一种将单亲遗传算法与最小元素法相结合的方法来处理此类问题，并且对遗传算法做了相应的改进，为了避免遗传算法的“早熟”现象，提高收敛速度，采用优化初始种群，自动调整交叉率和变异率的方法。采用这种混合算法的好处是削弱遗传算法的随机性，加快收敛，使算法的效率得到了提高。     

What was classical genetics?

I present an account of classical genetics to challenge theory-biased approaches in the philosophy of science. Philosophers typically assume that scientific knowledge is ultimately structured by explanatory reasoning and that research programs in well-established sciences are organized around efforts to fill out a central theory and extend its explanatory range. In the case of classical genetics, philosophers assume that the knowledge was structured by T. H. Morgan’s theory of transmission and that research throughout the later 1920s, 30s, and 40s was organized around efforts to further validate, develop, and extend this theory. I show that classical genetics was structured by an integration of explanatory reasoning (associated with the transmission theory) and investigative strategies (such as the ‘genetic approach’). The investigative strategies, which have been overlooked in historical and philosophical accounts, were as important as the so-called laws of Mendelian genetics. By the later 1920s, geneticists of the Morgan school were no longer organizing research around the goal of explaining inheritance patterns; rather, they were using genetics to investigate a range of biological phenomena that extended well beyond the explanatory domain of transmission theories. Theory-biased approaches in history and philosophy of science fail to reveal the overall structure of scientific knowledge and obscure the way it functions.     

Genetic ecology: A new interdisciplinary science,fundamental for evolution,biodiversity and biosafety evaluations

Genetic ecology is the extension of our modern knowledge in molecular genetics to studies of viability, gene expression and gene movements in natural environments like soils, aquifers and digestive tracts. In such milieux, the horizontal transfer of plasmid-borne genes between phylogenetically distant species has already been found to be much more frequent than had been expected from laboratory experience. For the study of exchanges involving chromosomally-located genes, more has to be learned about the behaviour of transposons in such environments. The results expected from studies in genetic ecology are relevant for considerations of evolution, biodiversity and biosafety. The role of this new field of research in restoring popular confidence in science and in its biotechnological applications is stressed.     

Population genetic structure and mating system evolution in freshwater pulmonates

Freshwater gastropods (Basommatophora and Prosobranchia) harbor a variety of mating systems. In particular, apomictic parthenogenesis in prosobranchs and self-fertilization in the hermaphrodite pulmonates may be viable alternatives to outcrossing sexuality in a number of species. The coexistence of different mating systems in extant populations provides opportunities to examine the forces directing their evolution. We review the models analyzing and predicting genetic variability in subdivided populations, with an emphasis on the effects of inbreeding. Population genetic data on freshwater pulmonates are examined in the context of selfing rates and the loss of variability under selfing. Furthermore, the genetic and demographic factors thought to influence mating system evolution are considered, and we highlight the different approaches available to estimate mating system parameters, in particular the selfing rate. Recent population biological studies on polyploid species (Bulinus truncatus, Ancylus fluviatilis) indicate that selfing is the predominant mating system. These studies have contributed to a deeper understanding of conceptual issues in the evolution of selfing rates. Throughout, we emphasize the need for further carefully designed studies.     

What Do We Measure When We Measure Aggression?

Biological research on aggression is increasingly consulted for possible answers to the social problems of crime and violence. This paper reviews some contrasting approaches to the biological understanding of behavior—behavioral genetic, social-environmental, physiological, developmental—as a prelude to arguing that approaches to aggression are beset by vagueness and imprecision in their definitions and disunity in their measurement strategies. This vagueness and disunity undermines attempts to compare and evaluate the different approaches empirically. Nevertheless, the definitions reveal commitments to particular metaphysical views concerning behavior. Alternative understandings of aggression suggest even different research approaches than those most commonly found in the literature.     

酸雨对植物影响的研究进展

本文综述了当前从种群和群落自然生态系统水平上、个体水平上、细胞水平上、生理生化水平上对酸雨对植物的影响研究，指出在分子遗传水平上研究酸雨生态效应及机理还有待进一步完善和发展。     

Selenium and selenoproteins in mammals: extraordinary,essential, enigmatic

Selenium (Se), once known only for its potential toxicity, is now well established as an essential trace element for mammals. Insufficient Se intake predisposes to and manifests in a variety of diseases. Recent studies have proven that it is the synthesis of selenocysteine (Sec)-containing proteins, designated selenoproteins, which represents an essential prerequisite for regular development and a long and healthy life. New transgenic mouse models analysing those selenoproteins with proven enzymatic functions displayed particular phenotypes and highlighted essential Se-dependent processes in development, growth or against specific challenges. While there is a growing molecular understanding of and general agreement on the importance of sufficiently high Se intake and undisturbed selenoprotein biosynthesis, many of the recently identified selenoproteins are still uncharacterised, and the effects and consequences of supra-physiological Se dosages are not biochemically understood. With the recent definition of the human and mouse selenoproteomes and a growing number of available tools, the Se field is now geared for a great leap forward. Se biology has already broadened our knowledge about the genetic code and about protein translation. It now holds great promises also for a better understanding of some key aspects of cancer, inflammation, fertility and prevention of age-associated diseases.Received 17 March 2004; received after revision 29 April 2004; accepted 27 May 2004