The genome-centric concept: resynthesis of evolutionary theory
ABSTRACT 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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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.03/2012; 26(2):117-24. DOI:10.1016/S1674-8301(12)60021-9
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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.Genomics 05/2011; 98(4):242-52. DOI:10.1016/j.ygeno.2011.05.008 · 2.79 Impact Factor
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ABSTRACT: Evolutionary approaches to carcinogenesis have gained prominence in the literature and enhanced our understanding of cancer. However, an appreciation of neoplasia in the context of evolutionary transitions, particularly the transition from independent genes to a fully integrated genome, is largely absent. In the gene-genome evolutionary transition, mobile genetic elements (MGEs) can be studied as the extant exemplars of selfish autonomous lower-level units that cooperated to form a higher-level, functionally integrated genome. Here, we discuss levels of selection in cancer cells. In particular, we examine the tension between gene and genome units of selection by examining the expression profiles of MGE domains in an array of human cancers. Overall, across diverse cancers, there is an aberrant expression of several families of mobile elements, including the most common MGE in the human genome, retrotransposon LINE 1. These results indicate an alternative life-history strategy for MGEs in the cancers studied. Whether the aberrant expression is the cause or effect of tumourigenesis is unknown, although some evidence suggests that dysregulation of MGEs can play a role in cancer origin and progression. These data are interpreted in combination with phylostratigraphic reports correlating the origin of cancer genes with multicellularity and other potential increases in complexity in cancer cell populations. Cooperation and conflict between individuals at the gene, genome and cell level provide an evolutionary medicine perspective of cancer that enhances our understanding of disease pathogenesis and treatment.South African Journal of Science 12/2011; 108(9-10):1-5. DOI:10.4102/sajs.v108i9/10.1002 · 1.03 Impact Factor