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: 4.84). 05/2009; 31(5):512-25. DOI: 10.1002/bies.200800182
Source: PubMed

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.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: LINE-1 retrotransposons encode the reverse transcriptase (RT) enzyme, required for their own mobility, the expression of which is inhibited in differentiated tissues while being active in tumors. Experimental evidence indicate that the inhibition of LINE-1-derived RT restores differentiation in cancer cells, inhibits tumor progression and yields globally reprogrammed transcription profiles. Newly emerging data suggest that LINE-1-encoded RT modulates the biogenesis of miRNAs, by governing the balance between the production of regulatory double-stranded RNAs and RNA:DNA hybrid molecules, with a direct impact on global gene expression. Abnormally high RT activity unbalances the transcriptome in cancer cells, while RT inhibition restores 'normal' miRNA profiles and their regulatory networks. This RT-dependent mechanism can target the myriad of transcripts - both coding and non-coding, sense and antisense - in eukaryotic transcriptomes, with a profound impact on cell fates. LINE-1-encoded RT emerges therefore as a key regulator of a previously unrecognized mechanism in tumorigenesis.
    Oncotarget 09/2014; 5(18):8039-51. · 6.63 Impact Factor
  • Source
    Conhecer para Preservar-Conhecer para Divulgar. Carta-Galeria Arqueológico-Histórica do Concelho de Vila Nova da Barquinha, Edited by Centro de Pré-História do Instituto Politécnico de Tomar, 12/2014: chapter A Grande Caminhada: pages 16-43; Centro de Pré-História do Instituto Politécnico de Tomar., ISBN: 978-972-9473-86-9
  • [Show abstract] [Hide abstract]
    ABSTRACT: The basis for the gene mutation theory of cancer that dominates current molecular cancer research consists of: the belief that gene-level aberrations such as mutations are the main cause of cancers, the concept that stepwise gene mutation accumulation drives cancer progression, and the hallmarks of cancer. The research community swiftly embraced the hallmarks of cancer, as such synthesis has supported the notions that common cancer genes are responsible for the majority of cancers and the complexity of cancer can be dissected into simplified molecular principles. The gene/pathway classification based on individual hallmarks provides explanation for the large number of diverse gene mutations, which is in contrast to the original estimation that only a handful of gene mutations would be discovered. Further, these hallmarks have been highly influential as they also provide the rationale and research direction for continued gene-based cancer research. While the molecular knowledge of these hallmarks is drastically increasing, the clinical implication remains limited, as cancer dynamics cannot be summarized by a few isolated/fixed molecular principles. Furthermore, the highly heterogeneous genetic signature of cancers, including massive stochastic genome alterations, challenges the utility of continuously studying each individual gene mutation under the framework of these hallmarks. It is therefore necessary to re-evaluate the concept of cancer hallmarks through the lens of cancer evolution. In this analysis, the evolutionary basis for the hallmarks of cancer will be discussed and the evolutionary mechanism of cancer suggested by the genome theory will be employed to unify the diverse molecular mechanisms of cancer. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 05/2015; 136(9). DOI:10.1002/ijc.29031 · 5.01 Impact Factor