Do plant and human pathogens have a common pathogenicity strategy?

Recently, a novel 'two-step' model of pathogenicity has been described that suggests host-cell-derived vasculoproliferative factors play a crucial role in the pathogenesis of bacillary angiomatosis, a disease caused by the human pathogenic bacterium Bartonella henselae. The resulting proliferation of endothelial cells could be interpreted as bacterial pathogens triggering the promotion of their own habitat: the host cell. Similar disease mechanisms are well known in the plant pathogen Agrobacterium tumefaciens, which causes crown gall disease. There are notable similarities between the pathogenicity of A. tumefaciens leading to tumourous disease in plants and to the B. henselae-triggered proliferation of endothelial cells in humans. Here, we hypothesize that this pathogenicity strategy might be common to several bacterial species in different hosts owing to shared pathogenicity factors.     

Adeno-associated virus: a key to the human genome?

Adeno-associated viruses (AAV) are widely spread throughout the human population, yet no pathology has been associated with infection. This fact, together with the availability of simple molecular techniques to alter the packaged viral genome, has made AAV a serious contender in the search for an ideal gene therapy delivery vehicle. However, our understanding of the intriguing features of this virus is far from exhausted and it is likely that the mechanisms underlying the viral lifestyle will reveal possible novel strategies that can be employed in future clinical approaches. One such aspect is the unique approach AAV has evolved in order to establish latency. In the absence of a cellular milieu that will support productive viral replication, wild-type AAV can integrate its genome site specifically into a locus on human chromosome 19 (termed AAVS1), where it resides without apparent effects on the host cell until cellular conditions are changed by outside influences, such as adenovirus super-infection, which will lead to the rescue of the viral genome and productive replication. This article will introduce the biology of AAV, the unique viral strategy of targeted genome integration and address relevant questions within the context of attempts to establish therapeutic approaches that will utilize targeted gene addition to the human genome.     

The regulation of autophagy by calcium signals: Do we have a consensus?

Macroautophagy (hereafter called ‘autophagy’) is a cellular process for degrading and recycling cellular constituents, and for maintenance of cell function. Autophagy initiates via vesicular engulfment of cellular materials and culminates in their degradation via lysosomal hydrolases, with the whole process often being termed ‘autophagic flux’. Autophagy is a multi-step pathway requiring the interplay of numerous scaffolding and signalling molecules. In particular, orthologs of the family of ∼30 autophagy-regulating (Atg) proteins that were first characterised in yeast play essential roles in the initiation and processing of autophagic vesicles in mammalian cells. The serine/threonine kinase mTOR (mechanistic target of rapamycin) is a master regulator of the canonical autophagic response of cells to nutrient starvation. In addition, AMP-activated protein kinase (AMPK), which is a key sensor of cellular energy status, can trigger autophagy by inhibiting mTOR, or by phosphorylating other downstream targets. Calcium (Ca²⁺) has been implicated in autophagic signalling pathways encompassing both mTOR and AMPK, as well as in autophagy seemingly not involving these kinases. Numerous studies have shown that cytosolic Ca²⁺ signals can trigger autophagy. Moreover, introduction of an exogenous chelator to prevent cytosolic Ca²⁺ signals inhibits autophagy in response to many different stimuli, with suggestions that buffering Ca²⁺ affects not only the triggering of autophagy, but also proximal and distal steps during autophagic flux. Observations such as these indicate that Ca²⁺ plays an essential role as a pro-autophagic signal. However, cellular Ca²⁺ signals can exert anti-autophagic actions too. For example, Ca²⁺ channel blockers induce autophagy due to the loss of autophagy-suppressing Ca²⁺ signals. In addition, the sequestration of Ca²⁺ by mitochondria during physiological signalling appears necessary to maintain cellular bio-energetics, thereby suppressing AMPK-dependent autophagy. This article attempts to provide an integrated overview of the evidence for the proposed roles of various Ca²⁺ signals, Ca²⁺ channels and Ca²⁺ sources in controlling autophagic flux.     

Do exogenous polyamines have an impact on the response of a salt-sensitive rice cultivar to NaCl?

In order to analyze the putative impact of polyamines (PAs) on the plant response to salt, seedlings from the salt-sensitive rice cultivar I Kong Pao (IKP) were exposed for 5, 12 and 19 days to 0, 50 or 100 mM NaCl in the absence, or in the presence of exogenous PAs (putrescine (Put), spermidine (Spd) or spermine (Spm) 1mM) or inhibitors of PA synthesis (methylglyoxalbis-guanyl hydrazone (MGBG) 1mM, cyclohexylammonium (CHA) 5mM and D-arginine (D-Arg) 5mM). The addition of PAs in nutritive solution reduced plant growth in the absence of NaCl and did not afford protection in the presence of salt. PA-treated plants exhibited a higher K+/Na+ ratio in the shoots, suggesting an improved discrimination among monovalent cations at the root level, especially at the sites of xylem loading. The diamine Put induced a decrease in the shoot water content in the presence of NaCl, while Spd and Spm had no effects on the plant water status. In contrast to Spd, Spm was efficiently translocated to the shoots. Both PAs (Spd and Spm) induced a decrease in cell membrane stability as suggested by a strong increase in malondialdehyde content of PA-treated plants exposed to NaCl. These results are discussed in relation to the putative functions of PAs in stressed plant metabolism.     

Do we have the auxin receptor yet?

Several auxin-binding proteins (ABP) have now been identified using a variety of techniques. A 43-kDa glycoprotein thought to be a dimer of 22-kDa subunits has been identified as a strong candidate for the auxin receptor that mediates cell elongation in etiolated maize shoots. The primary sequence has been deduced and several interesting structural features have been discerned. There is indirect evidence that this 22-kDa ABP has a receptor function, the most compelling being that antibodies directed against the ABP can block an auxin-induced response. There is evidence that changes in auxin-induced growth capacity in shoots correlates with changes in the abundance of the 22-kDa ABP suggesting that in some cases the 22-kDa ABP may be limiting growth. Confirmation of receptor function for one of these newly-identified ABP's should open the way for genetic manipulation of crop growth.     

Industrial melanism: Do we have the answers?

Entomologists from the late 19th century onwards recognized the evolutionary interest of the association of black forms of the peppered moth with industrialization. They developed a qualitative explanation of the phenomenon involving a change in relative crypsis of the phenotypes due to the blackening of the moth's resting background by air pollution. More recently, ecological geneticists have obtained some estimates of predation by birds and of population parameters such as migration rate. Models incorporating these estimates have explored the ways in which natural selection influences spatial variation and the maintenance of polymorphism. Studies on the peppered moth and some of the many other insects exhibiting industrial melanism have concentrated on the variability and dynamics of adult populations. Recent work which has begun to examine the ecology and behaviour of individuals, complete life cycles, and gene-phenotype relationships, is refining our understanding of this adaptation and also of present-day declines in melanic frequencies in response to falling air pollution.     

Do disparate mechanisms of duplication add similar genes to the genome?

Gene duplication is the fundamental source of new genes. Biases in duplication have profound implications for the dynamics of gene content during evolution. In this article, we compare genes arising from whole gene duplication (WGD), smaller scale duplication (SSD) and singletons in Saccharomyces cerevisiae. Our results demonstrate that genes duplicated by WGD and SSD are similarly biased with respect to codon bias and evolutionary rate, although differing significantly in their functional constituency.     

Do proteins learn to evolve? The Hopfield network as a basis for the understanding of protein evolution

Correlations between amino-acid residues can be observed in sets of aligned protein sequences, and the analysis of their statistical and evolutionary significance and distribution has been thoroughly investigated. In this paper, we present a model based on such covariations in protein sequences in which the pairs of residues that have mutual influence combine to produce a system analogous to a Hopfield neural network. The emergent properties of such a network, such as soft failure and the connection between network architecture and stored memory, have close parallels in known proteins. This model suggests that an explanation for observed characters of proteins such as the diminution of function by substitutions distant from the active site, the existence of protein folds (superfolds) that can perform several functions based on one architecture, and structural and functional resilience to destabilizing substitutions might derive from their inherent network-like structure. This model may also provide a basis for mapping the relationship between structure, function and evolutionary history of a protein family, and thus be a powerful tool for rational engineering.     

Is a genome a codeword of an error-correcting code?

Since a genome is a discrete sequence, the elements of which belong to a set of four letters, the question as to whether or not there is an error-correcting code underlying DNA sequences is unavoidable. The most common approach to answering this question is to propose a methodology to verify the existence of such a code. However, none of the methodologies proposed so far, although quite clever, has achieved that goal. In a recent work, we showed that DNA sequences can be identified as codewords in a class of cyclic error-correcting codes known as Hamming codes. In this paper, we show that a complete intron-exon gene, and even a plasmid genome, can be identified as a Hamming code codeword as well. Although this does not constitute a definitive proof that there is an error-correcting code underlying DNA sequences, it is the first evidence in this direction.     

Commentary: Do we have a consistent terminology for species diversity? The fallacy of true diversity

There is no single best index that can be used to answer all questions about species diversity. Entropy-based diversity indices, including Hill’s indices, cannot account for geographical and phylogenetic structure. While a single diversity index arises if we impose several constraints—most notably that gamma diversity be completely decomposed into alpha and beta diversity—there are many ecological questions regarding species diversity for which it is counterproductive, requiring decomposability. Non-decomposable components of gamma diversity may quantify important intrinsic ecological properties, such as resilience or nestedness.     

What's in a genome? The C-value enigma and the evolution of eukaryotic genome content

Some notable exceptions aside, eukaryotic genomes are distinguished from those of Bacteria and Archaea in a number of ways, including chromosome structure and number, repetitive DNA content, and the presence of introns in protein-coding regions. One of the most notable differences between eukaryotic and prokaryotic genomes is in size. Unlike their prokaryotic counterparts, eukaryotes exhibit enormous (more than 60 000-fold) variability in genome size which is not explained by differences in gene number. Genome size is known to correlate with cell size and division rate, and by extension with numerous organism-level traits such as metabolism, developmental rate or body size. Less well described are the relationships between genome size and other properties of the genome, such as gene content, transposable element content, base pair composition and related features. The rapid expansion of ‘complete’ genome sequencing projects has, for the first time, made it possible to examine these relationships across a wide range of eukaryotes in order to shed new light on the causes and correlates of genome size diversity. This study presents the results of phylogenetically informed comparisons of genome data for more than 500 species of eukaryotes. Several relationships are described between genome size and other genomic parameters, and some recommendations are presented for how these insights can be extended even more broadly in the future.     

The variability of the mitochondrial genome in human aging: a key for life and death?

The impressive performance of the research in mitochondrial genetics and human aging in the last decade outlines a new scenery in which the inherited variation of the mitochondrial genome (mtDNA) may play a role in rate and quality of aging. This variation in humans was initially looked at as nearly neutral, and useful just for the reconstruction of human population history. However, recent data suggest that different mtDNA molecules are qualitatively different from each other. The aim of this paper is to discuss current ideas on the relationships among mitochondrial function, mtDNA inherited variation, and aging. The main processes where the mitochondrion is involved and the importance these processes have on aging and death of individuals will be described. A possible connection between programmed death phenomena (mitoptosis, apoptosis, phenoptosis) and rate and quality of aging will be discussed. Finally, the possible role played in these processes by the mtDNA germline variation will be explored.