The genome-centric concept: Resynthesis of evolutionary theory
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA. BioEssays
(Impact Factor: 4.73).
05/2009; 31(5):512-25. DOI: 10.1002/bies.200800182
Modern biology has been heavily influenced by the gene-centric concept. Paradoxically, this very concept--on which bioresearch is based--is challenged by the success of gene-based research in terms of explaining evolutionary theory. To overcome this major roadblock, it is essential to establish new theories, to not only solve the key puzzles presented by the gene-centric concept, but also to provide a conceptual framework that allows the field to grow. This paper discusses a number of paradoxes and illustrates how they can be addressed by the genome-centric concept in order to further resynthesize evolutionary theory. In particular, methodological breakthroughs that analyze genome evolution are discussed. The multiple interactions among different levels of a complex system provide the key to understanding the relationship between self-organization and natural selection. Darwinian natural selection applies to the biological level due to its unique genetic and heterogeneous features, but does not simply or directly apply to either the lower non-living level or higher intellectual society level. At the complex bio-system level, the genome context (the entire package of genes and their genomic physical relationship or genomic topology), not the individual genes, defines the system and serves as the principle selection platform for evolution.
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Available from: Nicole Mcneil
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ABSTRACT: Anesthesia is widely used in several medical settings and accepted as safe. However, there is some evidence that anesthetic agents can induce genomic changes leading to neural degeneration or apoptosis. Although chromosomal changes have not been observed in vivo, this is most likely due to DNA repair mechanisms, apoptosis, or cellular senescence. Potential chromosomal alterations after exposure to common anesthetic agents may be relevant in patients with genomic instability syndromes or with aggressive treatment of malignancies. In this study, the P388 murine B cells were cultured in vitro, and spectral karyotyping (SKY) was utilized to uncover genome-wide changes. Clinically relevant doses of cisatracurium and propofol increased structural and numerical chromosomal instability. These results may be relevant in patients with underlying chromosomal instability syndromes or concurrently being exposed to chemotherapeutic agents. Future studies may include utilization of stimulated peripheral blood lymphocytes to further confirm the significance of these results.
Available from: Henry Heng
- "It is true that increasing attention has been given to the " gene context " rather than genes alone. However, without the conceptual framework of the genome theory, isolated approaches will not solve most paradoxes that the gene theory created  "
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ABSTRACT: While our understanding of gene-based biology has greatly improved, it is clear that the function of the genome and most diseases cannot be fully explained by genes and other regulatory elements. Genes and the genome represent distinct levels of genetic organization with their own coding systems; Genes code parts like protein and RNA, but the genome codes the structure of genetic networks, which are defined by the whole set of genes, chromosomes and their topological interactions within a cell. Accordingly, the genetic code of DNA offers limited understanding of genome functions. In this perspective, we introduce the genome theory which calls for the departure of gene-centric genomic research. To make this transition for the next phase of genomic research, it is essential to acknowledge the importance of new genome-based biological concepts and to establish new technology platforms to decode the genome beyond sequencing.
Available from: Joshua B Stevens
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ABSTRACT: Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused with chromosome fragmentation. In this analysis the phenomena of chromosome fragmentation and PCC are reviewed and their similarities and differences are discussed in order to facilitate differentiation of the similar morphologies. Furthermore, chromosome pulverization, which has been used almost synonymously with PCC, is re-examined. Interestingly, many past reports of chromosome pulverization are identified here as chromosome fragmentation and not PCC. These reports describe broad ranging mechanisms of pulverization induction and agree with recent evidence showing chromosome fragmentation is a cellular response to stress. Finally, biological aspects of chromosome fragmentation are discussed, including its application as one form of non-clonal chromosome aberration (NCCA), the driving force of cancer evolution.
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