Trends in genetics

Crosstalk between genetic and epigenetic information through cytosine deamination.

Publication Date: 2010 Aug 25 PMID: 20800313
Authors: Chahwan, R. - Wontakal, S. N. - Roa, S.
Journal: Trends Genet

Decades of work have elucidated the existence of two forms of heritable information, namely genetic and epigenetic, which are collectively referred to as the 'dual inheritance'. The underlying mechanisms behind these two modes of inheritance have so far remained distinct. Cytosine deaminases, such as activation-induced cytidine deaminase (AID) and other members of the APOBEC family, have been implicated both in genetic variation of somatic cells and in epigenetic remodeling of germ and pluripotent cells. We hereby synthesize these seemingly dissociated functions into one coherent model, and further suggest that cytosine deaminases, particularly AID, might have a broader influence by modulating epigenetic information in somatic or cancer cells, as well as by triggering genetic variation in germ and pluripotent cells through mutation followed by natural selection. We therefore propose that the AID/APOBEC family of deaminases are likely to have acted as drivers throughout vertebrate evolution.

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Secondary metabolic gene clusters: evolutionary toolkits for chemical innovation.

Publication Date: 2010 Aug 23 PMID: 20739089
Authors: Osbourn, A.
Journal: Trends Genet

Microbes and plants produce a huge array of secondary metabolites that have important ecological functions. These molecules have long been exploited in medicine as antibiotics, anticancer and anti-infective agents and for a wide range of other applications. Gene clusters for secondary metabolic pathways are common in bacteria and filamentous fungi, and examples have now been discovered in plants. Here, current knowledge of gene clusters across the kingdoms is evaluated with the aim of trying to understand the rules behind cluster existence and evolution. Such knowledge will be crucial in learning how to activate the enormous number of 'silent' gene clusters being revealed by whole-genome sequencing and hence in making available a wealth of novel compounds for evaluation as drug leads and other bioactives. It could also facilitate the development of crop plants with enhanced pest or disease resistance, improved nutritional qualities and/or elevated levels of high-value products.

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Maintenance of duplicate genes and their functional redundancy by reduced expression.

Publication Date: 2010 Aug 11 PMID: 20708291
Authors: Qian, W. - Liao, B. Y. - Chang, A. Y. - Zhang, J.
Journal: Trends Genet

Although evolutionary theories predict functional divergence between duplicate genes, many old duplicates still maintain a high degree of functional similarity and are synthetically lethal or sick, an observation that has puzzled many geneticists. We propose that expression reduction, a special type of subfunctionalization, facilitates the retention of duplicates and the conservation of their ancestral functions. Consistent with this hypothesis, gene expression data from both yeasts and mammals show a substantial decrease in the level of gene expression after duplication. Whereas the majority of the expression reductions are likely to be neutral, some are apparently beneficial to rebalancing gene dosage after duplication.

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Mimivirus: the emerging paradox of quasi-autonomous viruses.

Publication Date: 2010 Aug 7 PMID: 20696492
Authors: Claverie, J. M. - Abergel, C.
Journal: Trends Genet

What is a virus? Are viruses alive? Should they be classified among microorganisms? One would expect these simple questions to have been settled a century after the discovery of the first viral disease. For years, modern virology successfully unravelled the huge diversity of viruses in terms of genetic material, replication mechanism, pathogenicity, host infection, and more recently particle structure, planet-wide distribution and ecological significance. Yet, little progress was made in understanding their evolutionary origin(s), as well as the fundamental nature of their relationship with the cellular world. Thanks to the recent studies on Mimivirus and other large DNA viruses, we are now entering a new era where the most basic concepts about viruses are revisited, including their true nature, how fundamentally different they are from cellular microorganisms, and how essential they might have been in the major innovations that punctuated the evolution of life.

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Psoriasis genetics: breaking the barrier.

Publication Date: 2010 Sep PMID: 20692714
Authors: Roberson, E. D. - Bowcock, A. M.
Journal: Trends Genet

Psoriasis is a common incurable inflammatory skin disease affecting 2-3% of the European population. Psoriatic skin contains large numbers of immune cells which produce many cytokines, chemokines and inflammatory molecules. The epidermis divides much faster than normal and has a defective outer layer or barrier which under normal circumstances protects from infection and dehydration. Psoriatic skin is characterized by a distinct set of inflammation and epidermal proliferation and differentiation markers, and it has been unclear whether the genetic basis of psoriasis reflects defects of the immune system or of the skin. One genetic determinant lies within the major histocompatibility complex class 1 region. Genome-wide association studies have revealed genetic susceptibility factors that play a role in the formation of immune cells found in psoriasis lesions. Others affect epidermal proliferation and skin barrier formation. Hence, genetic components of both the immune system and the epidermis can predispose to disease.

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Causes and evolutionary significance of genetic convergence.

Publication Date: 2010 Sep PMID: 20685006
Authors: Christin, P. A. - Weinreich, D. M. - Besnard, G.
Journal: Trends Genet

Convergent phenotypes provide extremely valuable systems for studying the genetics of new adaptations. Accumulating studies on this topic have reported surprising cases of convergent evolution at the molecular level, ranging from gene families being recurrently recruited to identical amino acid replacements in distant lineages. Together, these different examples of genetic convergence suggest that molecular evolution is in some cases strongly constrained by a combination of limited genetic material suitable for new functions and a restricted number of substitutions that can confer specific enzymatic properties. We discuss approaches for gaining further insights into the causes of genetic convergence and their potential contribution to our understanding of how the genetic background determines the evolvability of complex organismal traits.

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Lineage-specific expansion of DNA-binding transcription factor families.

Publication Date: 2010 Sep PMID: 20675012
Authors: Charoensawan, V. - Wilson, D. - Teichmann, S. A.
Journal: Trends Genet

DNA-binding domains (DBDs) are essential components of sequence-specific transcription factors (TFs). We have investigated the distribution of all known DBDs in more than 500 completely sequenced genomes from the three major superkingdoms (Bacteria, Archaea and Eukaryota) and documented conserved and specific DBD occurrence in diverse taxonomic lineages. By combining DBD occurrence in different species with taxonomic information, we have developed an automatic method for inferring the origins of DBD families and their specific combinations with other protein families in TFs. We found only three out of 131 (2%) DBD families shared by the three superkingdoms.

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Increased sequence conservation of domain repeats in prokaryotic proteins.

Publication Date: 2010 Sep PMID: 20643491
Authors: Reshef, D. - Itzhaki, Z. - Schueler-Furman, O.
Journal: Trends Genet

Protein domain repeats within a protein sequence have been observed throughout all domains of life. Our analysis shows a significantly higher degree of sequence identity between repeated domains in prokaryotes compared to eukaryotes. We discuss this difference in the light of aggregation prevention, contribution to functional divergence and binding-related functions. We then address the possible underlying features that create and conserve domain repeats. Our findings provide a starting point for the identification of the fundamental principles that underlie this basic difference between eukaryotic and prokaryotic protein evolution.

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DNA methylation reprogramming during plant sexual reproduction?

Publication Date: 2010 Sep PMID: 20609490
Authors: Jullien, P. E. - Berger, F.
Journal: Trends Genet

Chromatin modifications including histone marks and DNA methylation restrict the transcriptional repertoire and participate in cell fate establishment. Conservation of modified chromatin states through cell division and their inheritance through meiosis create mitotic and trans-generational forms of epigenetic memory, respectively. This lies in apparent contradiction with the requirement to reset cell-fate instructive chromatin states between generations. Although DNA methylation is reset in mammals, its resetting in plants remains controversial, and several lines of evidence support trans-generational inheritance of DNA methylation. Based on recent reports we propose that DNA demethylation during female gametogenesis is followed by DNA remethylation during early embryo development. We propose that this reprogramming event is achieved through interplay between active and passive mechanisms that involve both DNA demethylation and de novo DNA methylation.

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Robustness and evolvability.

Publication Date: 2010 Sep PMID: 20598394
Authors: Masel, J. - Trotter, M. V.
Journal: Trends Genet

Why isn't random variation always deleterious? Are there factors that sometimes make adaptation easier? Biological systems are extraordinarily robust to perturbation by mutations, recombination and the environment. It has been proposed that this robustness might make them more evolvable. Robustness to mutation allows genetic variation to accumulate in a cryptic state. Switching mechanisms known as evolutionary capacitors mean that the amount of heritable phenotypic variation available can be correlated to the degree of stress and hence to the novelty of the environment and remaining potential for adaptation. There have been two somewhat separate literatures relating robustness to evolvability. One has focused on molecular phenotypes and new mutations, the other on morphology and cryptic genetic variation. Here, we review both literatures, and show that the true distinction is whether recombination rates are high or low. In both cases, the evidence supports the claim that robustness promotes evolvability.

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