Although mutation provides the fuel for phenotypic evolution, it also imposes a substantial burden on fitness through the production of predominantly deleterious alleles, a matter of concern from a ...human-health perspective. Here, recently established databases on de novo mutations for monogenic disorders are used to estimate the rate and molecular spectrum of spontaneously arising mutations and to derive a number of inferences with respect to eukaryotic genome evolution. Although the human per-generation mutation rate is exceptionally high, on a per-cell division basis, the human germline mutation rate is lower than that recorded for any other species. Comparison with data from other species demonstrates a universal mutational bias toward A/T composition, and leads to the hypothesis that genome-wide nucleotide composition generally evolves to the point at which the power of selection in favor of G/C is approximately balanced by the power of random genetic drift, such that variation in equilibrium genome-wide nucleotide composition is largely defined by variation in mutation biases. Quantification of the hazards associated with introns reveals that mutations at key splice-site residues are a major source of human mortality. Finally, a consideration of the long-term consequences of current human behavior for deleterious-mutation accumulation leads to the conclusion that a substantial reduction in human fitness can be expected over the next few centuries in industrialized societies unless novel means of genetic intervention are developed.
The profound influence of microorganisms on human life and global biogeochemical cycles underlines the value of studying the biogeography of microorganisms, exploring microbial genomes and expanding ...our understanding of most microbial species on Earth: that is, those present at low relative abundance. The detection and subsequent analysis of low-abundance microbial populations—the 'rare biosphere'—have demonstrated the persistence, population dynamics, dispersion and predation of these microbial species. We discuss the ecology of rare microbial populations, and highlight molecular and computational methods for targeting taxonomic 'blind spots' within the rare biosphere of complex microbial communities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The vast majority of biologists engaged in evolutionary studies interpret virtually every aspect of biodiversity in adaptive terms. This narrow view of evolution has become untenable in light of ...recent observations from genomic sequencing and population-genetic theory. Numerous aspects of genomic architecture, gene structure, and developmental pathways are difficult to explain without invoking the nonadaptive forces of genetic drift and mutation. In addition, emergent biological features such as complexity, modularity, and evolvability, all of which are current targets of considerable speculation, may be nothing more than indirect by-products of processes operating at lower levels of organization. These issues are examined in the context of the view that the origins of many aspects of biological diversity, from gene-structural embellishments to novelties at the phenotypic level, have roots in nonadaptive processes, with the population-genetic environment imposing strong directionality on the paths that are open to evolutionary exploitation.
Although the human germline mutation rate is higher than that in any other well-studied species, the rate is not exceptional once the effective genome size and effective population size are taken ...into consideration. Human somatic mutation rates are substantially elevated above those in the germline, but this is also seen in other species. What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern. Ultimately, the price will have to be covered by further investment in various forms of medical intervention. Resolving the uncertainties of the magnitude and timescale of these effects will require the establishment of stable, standardized, multigenerational measurement procedures for various human traits.
Massively parallel sequencing of 16S rRNA genes enables the comparison of terrestrial, aquatic, and host-associated microbial communities with sufficient sequencing depth for robust assessments of ...both alpha and beta diversity. Establishing standardized protocols for the analysis of microbial communities is dependent on increasing the reproducibility of PCR-based molecular surveys by minimizing sources of methodological bias. In this study, we tested the effects of template concentration, pooling of PCR amplicons, and sample preparation/interlane sequencing on the reproducibility associated with paired-end Illumina sequencing of bacterial 16S rRNA genes. Using DNA extracts from soil and fecal samples as templates, we sequenced pooled amplicons and individual reactions for both high (5- to 10-ng) and low (0.1-ng) template concentrations. In addition, all experimental manipulations were repeated on two separate days and sequenced on two different Illumina MiSeq lanes. Although within-sample sequence profiles were highly consistent, template concentration had a significant impact on sample profile variability for most samples. Pooling of multiple PCR amplicons, sample preparation, and interlane variability did not influence sample sequence data significantly. This systematic analysis underlines the importance of optimizing template concentration in order to minimize variability in microbial-community surveys and indicates that the practice of pooling multiple PCR amplicons prior to sequencing contributes proportionally less to reducing bias in 16S rRNA gene surveys with next-generation sequencing.
Ontography Lynch, Michael
Social studies of science,
06/2013, Letnik:
43, Številka:
3
Journal Article
Recenzirano
In this postscript to the special issue of Social Studies of Science on the ‘turn to ontology’ in science and technology studies, I discuss a tension that runs through many of the articles in the ...issue. This is a tension between adopting a general philosophical ontology and pursuing empirical studies of particular historical and contemporary practices. The general ontology highlights multiplicity and difference and rejects the idea that, for example, an identical disease entity underlies different practical enactments of that disease in different clinical and research circumstances. The empirical approach investigates how particular identities and differences are negotiated and instantiated in specific circumstances. The two approaches are not necessarily incompatible, but the first settles questions of identity and difference through a ‘pre-theoretical decision’, while the second remains open to distinct resolutions of what counts as identity and difference in the practical settings studied. In this postscript, I argue that a commitment to a general philosophical ontology confuses investigations of specific practical ontologies. To avoid such confusion, I recommend ‘ontography’: historical and ethnographic investigations of particular world-making and world-sustaining practices that do not begin by assuming a general picture of the world. Such investigations avoid making sharp distinctions between epistemology and ontology and take a symmetrical approach to concerns about identity and difference.
Although numerous investigators assume that the global features of genetic networks are moulded by natural selection, there has been no formal demonstration of the adaptive origin of any genetic ...network. This Analysis shows that many of the qualitative features of known transcriptional networks can arise readily through the non-adaptive processes of genetic drift, mutation and recombination, raising questions about whether natural selection is necessary or even sufficient for the origin of many aspects of gene-network topologies. The widespread reliance on computational procedures that are devoid of population-genetic details to generate hypotheses for the evolution of network configurations seems to be unjustified.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
One of the most striking features of proteins is their common assembly into multimeric structures, usually homomers with even numbers of subunits all derived from the same genetic locus. However, ...although substantial structural variation for orthologous proteins exists within and among major phylogenetic lineages, in striking contrast to patterns of gene structure and genome organization, there appears to be no correlation between the level of protein structural complexity and organismal complexity. In addition, there is no evidence that protein architectural differences are driven by lineage-specific differences in selective pressures. Here, it is suggested that variation in the multimeric states of proteins can readily arise from stochastic transitions resulting from the joint processes of mutation and random genetic drift, even in the face of constant directional selection for one particular protein architecture across all lineages. Under the proposed hypothesis, on a long evolutionary timescale, the numbers of transitions from monomers to dimers should approximate the numbers in the opposite direction and similarly for transitions between higher-order structures.
This volume includes an unpublished manuscript and selected portions of five seminars by Harold Garfinkel – the founder of ethnomethodology – on the topic of practices in the natural sciences and ...mathematics. The volume provides a coherent and sustained account of his program for the study of ordinary and specialized social actions. Presenting broader theoretical and methodological initiatives, as well as discussions and summaries of exemplary studies of social phenomena within and beyond the sciences, this work dates to the period in the 1980s during which the field of Science and Technology Studies was taking shape, with ethnomethodological studies of scientific practice forming a major part of its development at the time. Aside from their historical importance, the manuscript and seminars present a distinctive perspective on the natural and social sciences that remains highly original and pertinent to research on science, social science, and everyday life today. Offering critical insights and proposals relating to developments in Ethnomethodology and Conversation Analysis, this volume will appeal to scholars of Sociology and Science and Technology Studies with interests in the work of Garfinkel.
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