As we come to the end of 2011, several members of the Genome Biology Editorial Board give their views on the state of play in genomics

As we come to the end of 2011, Genome Biology has asked some members of our Editorial Board for their views on the state of play in genomics. What was their favorite paper of 2011? What are the challenges in their particular research area? Who has had the biggest influence on their careers? What advice would they give to young researchers embarking on a career in research?     

Efficient TDZ-induced regeneration from capitulum explants of Gerbera jamesonii Bolus ex Hooker F. - an ornamental plant with high aesthetic value

Gerbera jamesonii Bolus ex Hooker F. (Asteraceae), a most prominent ornamental plant ranking fifth in the world cut flower market has gained huge demand across the globe for its high aesthetic value. In the present study, an efficient plant regeneration protocol was developed using capitulum explants from the field grown mature plants of G. jamesonii. A successful surface sterilization procedure was established using a series of sterilants without affecting explant regenerability. The culture of capitulum explants on Pre-culture Induction Medium [(PIM), Murashige and Skoog (MS) medium fortified with 0.5?mg/L thidiazuron (TDZ) in combination with low levels of auxins] for a period of 2 weeks in dark conditions was crucial for inducing morphogenetic response. Upon transfer onto Shoot Regeneration Medium [(SRM), MS +4.0?mg/L 6-benzyladenine (BA) and 0.2?mg/L NAA], explants has significantly produced highest number of shoots (16?±?0.33). Incubation for 18–21?days on Shoot Multiplication and Elongation Medium [(SMEM), MS +2.0?mg/L BA +0.2?mg/L NAA] resulted in the highest number of multiple shoots (22.00?±?0.93) with increased mean shoot length (3.49?±?0.08). In vitro elongated shoots were rooted (95%) on ½ MS +1.0?mg/L indole-3-acetic acid (IAA) within 10–12?days and fully rooted plants were transferred to poly-house for hardening with 90% survival rate.     

The genetics and molecular biology of the titin/connectin-like proteins of invertebrates

Conclusions A substantial amount of information has been gathered about the structure and function of twitchin/titin-related proteins in the invertebrates. This has been obtained through sequence analysis and the analysis of loss-offunction phenotypes inC. elegans andDrosophila. Nevertheless, a number of fascinating questions remain, including: (i) Why are these invertebrate proteins all of approx. 700–800 kDa? In terms of sarcomeric organization, what is the significance of this size? (ii) Why do three of these proteins consist of a mixture of Ig and Fn domains, whereas UNC-89 contains only Ig domains? This is even more interesting because the structures of Ig and Fn domains are very similar (118). What is the significance of the repeating pattern of groups of Ig and Fn domains (e.g. Fn-Fn-Ig)? (iii) How are twitchin and the synchronous muscle isoform of projectin situated on the surface of thick filaments? That is, do they form polymers or are they located at discrete locations with intervening gaps? (iv) What is the mechanism by which the fundamentally similar projectin isoforms get localized to different sarcomeric locations? (v) If the data onAplysia twitchin can be extended to the muscles of other invertebrates, what is the mechanism by which twitchin inhibits the rate of relaxation? How does phosphorylation of twitchin relieve this inhibition? (vi) What are the substrates for the protein kinase domains of nematode twitchin and insect projectin? If rMLCs are indeed the substrates, how would and why does this phosphorylation take place for the IFM isoform of projectin, which resides primarily in the I band? If rMLCs are the substrates, given the stoichiometry of approx. 1∶50 for twitchin:myosin, and the likely fixed position of twitchin along the thick filament, how does phosphorylation of just a few rMLCs result in a physiological effect (e.g. inhibition of relaxation)? What is the true activator for the twitchin and projectin kinases? (vii) How does UNC-89 participate in M-line assembly? (viii) What are the biochemical and physiological functions of intestinal brush border twitchin? A number of investigators will enjoy pursuing these and other questions for some time in the future.     

Establishing gene function by mutagenesis in Arabidopsis thaliana

The nuclear genome of Arabidopsis thaliana was sequenced to near completion a few years ago, and ahead lies the challenge of understanding its meaning and discerning its potential. How many genes are there? What are they? What do they do? Computer algorithms combined with genome array technologies have proven efficient in addressing the first two questions as shown in a recent report ( Yamada et al., 2003 ). However, assessing the function of every gene in every cell will require years of careful analyses of the phenotypes caused by mutations in each gene. Current progress in generating large numbers of molecular markers and near‐saturation insertion mutant collections has immensely facilitated functional genomics studies in Arabidopsis. In this review, we focus on how gene function can be revealed through the analysis of mutants by either forward or reverse genetics. These mutants generally fall into two distinct classes. The first class typically includes point mutations or small deletions derived from chemical or fast neutron mutagenesis whereas the second class includes insertions of transferred‐DNA or transposon elements. We describe the current methods that are used to identify the gene corresponding to these mutations, which can then be used as a probe to further dissect its function.     

Estimating the minimum rate of genetic transformation in bacteria

Extensive data from multilocus electrophoresis are available for many bacterial populations. In some cases, for example Neisseria gonorrhoeae, these data are consistent with the population being in linkage equilibrium. This raises the following question. What frequency of transformation, or other means of genetic recombination, is needed, relative to mutation, to produce apparent panmixis? Simulation of a finite-population model suggests that, if transformation is at least twenty times as frequent as mutation, the population structure will be indistinguishable from a panmictic one, using the best available data sets. That is, relatively infrequent transformation is sufficient to produce approximate linkage equilibrium.     

Schema-based learning of adaptable and flexible prey-catching in anurans I. The basic architecture

A motor action often involves the coordination of several motor synergies and requires flexible adjustment of the ongoing execution based on feedback signals. To elucidate the neural mechanisms underlying the construction and selection of motor synergies, we study prey-capture in anurans. Experimental data demonstrate the intricate interaction between different motor synergies, including the interplay of their afferent feedback signals (Weerasuriya 1991; Anderson and Nishikawa 1996). Such data provide insights for the general issues concerning two-way information flow between sensory centers, motor circuits and periphery in motor coordination. We show how different afferent feedback signals about the status of the different components of the motor apparatus play a critical role in motor control as well as in learning. This paper, along with its companion paper, extend the model by Liaw et al. (1994) by integrating a number of different motor pattern generators, different types of afferent feedback, as well as the corresponding control structure within an adaptive framework we call Schema-Based Learning. We develop a model of the different MPGs involved in prey-catching as a vehicle to investigate the following questions: What are the characteristic features of the activity of a single muscle? How can these features be controlled by the premotor circuit? What are the strategies employed to generate and synchronize motor synergies? What is the role of afferent feedback in shaping the activity of a MPG? How can several MPGs share the same underlying circuitry and yet give rise to different motor patterns under different input conditions? In the companion paper we also extend the model by incorporating learning components that give rise to more flexible, adaptable and robust behaviors. To show these aspects we incorporate studies on experiments on lesions and the learning processes that allow the animal to recover its proper functioning     

Understanding the Human Genome Project: a biographical approach

This article analyzes a number of recently published autobiographies by leading participants in the Human Genome Project (HGP), in order to determine to what extent they may further our understanding of the history, scientific significance and societal impact of this major research endeavor. Notably, I will focus on three publications that fall under this heading, namely The common thread by John Sulston (2002/2003), The language of God (2006) by Francis Collins and A life decoded by Craig Venter (2007).1 Sulston's autobiography was co-authored by science writer Georgina Ferry. What may we learn from these autobiographical sources about the dynamics of scientific change? What is their added value in understanding science in general and the HGP in particular? These questions will be elaborated in three directions: on the level of knowledge (epistemology), power (politics) and the Self (ethics). On the epistemological level, genomics is often presented as a paradigm shift in the life sciences, a tremendous up-scaling of research, an “informatization” of life. Autobiographies may reveal how this shift – usually discussed in more general terms from a philosophy of science or science studies perspective – manifests itself on an individual scale, on a micro-epistemological level. On the political level, autobiographies may inform us about the micro-politics of scientific change. Finally, on the level of Self, autobiographies may allow us to analyze how researchers, through practices of Self, are actively engaged in constituting themselves as responsible subjects in the face of unpredictable dynamics and unforeseen dilemmas.     

Variegation mutants and mechanisms of chloroplast biogenesis

Variegated plants typically have green‐ and white‐sectored leaves. Cells in the green sectors contain normal‐appearing chloroplasts, whereas cells in the white sectors lack pigments and appear to be blocked at various stages of chloroplast biogenesis. Variegations can be caused by mutations in nuclear, chloroplast or mitochondrial genes. In some plants, the green and white sectors have different genotypes, but in others they have the same (mutant) genotype. One advantage of variegations is that they provide a means of studying genes for proteins that are important for chloroplast development, but for which mutant analysis is difficult, either because mutations in a gene of interest are lethal or because they do not show a readily distinguishable phenotype. This paper focuses on Arabidopsis variegations, for which the most information is available at the molecular level. Perhaps the most interesting of these are variegations caused by defective nuclear gene products in which the cells of the mutant have a uniform genotype. Two questions are of paramount interest: (1) What is the gene product and how does it function in chloroplast biogenesis? (2) What is the mechanism of variegation and why do green sectors arise in plants with a uniform (mutant) genotype? Two paradigms of variegation mechanism are described: immutans (im) and variegated2 (var2). Both mechanisms emphasize compensating activities and the notion of plastid autonomy, but redundant gene products are proposed to play a role in var2, but not in im. It is hypothesized that threshold levels of certain activities are necessary for normal chloroplast development.     

On the effect of phenotypic dimensionality on adaptation and optimality

What proportion of the traits of individuals has been optimally shaped by natural selection and what has not? Here, we estimate the maximal number of those traits using a mathematical model for natural selection in multitrait organisms. The model represents the most ideal conditions for natural selection: a simple genotype–phenotype map and independent variation between traits. The model is also used to disentangle the influence of fitness functions and the number of traits, n, per se on the efficiency of natural selection. We also allow n to evolve. Our simulations show that, for all fitness functions and even in the best conditions optimal phenotypes are rarely encountered, only for n = 1, and that a large proportion of traits are always far from their optimum, specially for large n. This happens to different degrees depending on the fitness functions (additive linear, additive nonlinear, Gaussian and multiplicative). The traits that arise earlier in evolution account for a larger proportion of the absolute fitness of individuals. Thus, complex phenotypes have, in proportion, more traits that are far from optimal and the closeness to the optimum correlates with the age of the trait. Based on estimated population sizes, mutation rates and selection coefficients, we provide an upper estimation of the number of traits that can become and remain adapted by direct natural selection.     

Health migration from Norway to Spain – ambiguous belonging

Abstract

In line with Gustafson (2008), most studies of transnationalism have investigated migration from south to north. This article examines health-, welfare- and lifestyle-related migration from Norway to Spain. The phenomenon is increasing, with consequences for national and municipal policies. The focus is on how Norwegian health migrants cope. Based on anthropological fieldwork and life story interviews we ask: Who are these migrants? How did the migration step come into being? How do they cope when the decision is effectuated? What kind of identity-related challenges do they face? The article also discusses implications for future comparative research on the phenomenon.     

Involvement of autophagy and mitochondrial dynamics in determining the fate and effects of irreparable mitochondrial DNA damage

Mitochondrial DNA (mtDNA) is different in many ways from nuclear DNA. A key difference is that certain types of DNA damage are not repaired in the mitochondrial genome. What, then, is the fate of such damage? What are the effects? Both questions are important from a health perspective because irreparable mtDNA damage is caused by many common environmental stressors including ultraviolet C radiation (UVC). We found that UVC-induced mtDNA damage is removed slowly in the nematode Caenorhabditis elegans via a mechanism dependent on mitochondrial fusion, fission, and autophagy. However, knockdown or knockout of genes involved in these processes—many of which have homologs involved in human mitochondrial diseases—had very different effects on the organismal response to UVC. Reduced mitochondrial fission and autophagy caused no or small effects, while reduced mitochondrial fusion had dramatic effects.     

Neuronal sub‐compartmentalization: a strategy to optimize neuronal function

Neurons are highly polarized cells that consist of three main structural and functional domains: a cell body or soma, an axon, and dendrites. These domains contain smaller compartments with essential roles for proper neuronal function, such as the axonal presynaptic boutons and the dendritic postsynaptic spines. The structure and function of these compartments have now been characterized in great detail. Intriguingly, however, in the last decade additional levels of compartmentalization within the axon and the dendrites have been identified, revealing that these structures are much more complex than previously thought. Herein we examine several types of structural and functional sub‐compartmentalization found in neurons of both vertebrates and invertebrates. For example, in mammalian neurons the axonal initial segment functions as a sub‐compartment to initiate the action potential, to select molecules passing into the axon, and to maintain neuronal polarization. Moreover, work in Drosophila melanogaster has shown that two distinct axonal guidance receptors are precisely clustered in adjacent segments of the commissural axons both in vivo and in vitro, suggesting a cell‐intrinsic mechanism underlying the compartmentalized receptor localization. In Caenorhabditis elegans, a subset of interneurons exhibits calcium dynamics that are localized to specific sections of the axon and control the gait of navigation, demonstrating a regulatory role of compartmentalized neuronal activity in behaviour. These findings have led to a number of new questions, which are important for our understanding of neuronal development and function. How are these sub‐compartments established and maintained? What molecular machinery and cellular events are involved? What is their functional significance for the neuron? Here, we reflect on these and other key questions that remain to be addressed in this expanding field of biology.     

Parallel and nonparallel behavioural evolution in response to parasitism and predation in Trinidadian guppies

Natural enemies such as predators and parasites are known to shape intraspecific variability of behaviour and personality in natural populations, yet several key questions remain: (i) What is the relative importance of predation vs. parasitism in shaping intraspecific variation of behaviour across generations? (ii) What are the contributions of genetic and plastic effects to this behavioural divergence? (iii) And to what extent are responses to predation and parasitism repeatable across independent evolutionary lineages? We addressed these questions using Trinidadian guppies (Poecilia reticulata) (i) varying in their exposure to dangerous fish predators and Gyrodactylus ectoparasites for (ii) both wild‐caught F0 and laboratory‐reared F2 individuals and coming from (iii) multiple independent evolutionary lineages (i.e. independent drainages). Several key findings emerged. First, a population's history of predation and parasitism influenced behavioural profiles, but to different extent depending on the behaviour considered (activity, shoaling or boldness). Second, we had evidence for some genetic effects of predation regime on behaviour, with differences in activity of F2 laboratory‐reared individuals, but not for parasitism, which had only plastic effects on the boldness of wild‐caught F0 individuals. Third, the two lineages showed a mixture of parallel and nonparallel responses to predation/parasitism, with parallel responses being stronger for predation than for parasitism and for activity and boldness than for shoaling. These findings suggest that different sets of behaviours provide different pay‐offs in alternative predation/parasitism environments and that parasitism has more transient effects in shaping intraspecific variation of behaviour than does predation.     

Growth releases of three shade‐tolerant species following canopy gap formation in old‐growth forests

Questions: Do the number, duration and magnitude of growth releases following formation of natural, fine‐scale canopy gaps differ among shade‐tolerant Thuja plicata, Tsuga heterophylla and Abies amabilis? What is the relative importance of tree‐level and gap‐level variables in predicting the magnitude and duration of releases? What does this tell us about mechanisms of tree species coexistence in such old‐growth forests? Location: Coastal British Columbia, Canada. Methods: We estimated the timing of formation of 20 gaps using dendroecological techniques and extracted increment cores from all three species growing around or within gaps. Using a species‐ and ecosystem‐specific release‐detection method, we determined the number of trees experiencing a release following gap formation. We quantified the duration and magnitude of individual releases and estimated the influence of tree‐level and gap‐level variables on these release attributes. Results: Eighty‐seven per cent (304 of 348) of all trees experienced a release following gap formation. T. heterophylla and A. amabilis experienced higher magnitude and longer duration releases than T. plicata. The effect of diameter on the duration of releases varied among species, with T. heterophylla and A. amabilis experiencing decreasing, and T. plicata experiencing increasing, duration of releases with increasing diameter. The effect of growth rate prior to a release on the magnitude of releases varied among trees of different diameters, with the slowest growing and smallest individuals of all species experiencing the most intensive releases. Conclusions: Our results provide detailed information on the number, duration and magnitude of growth releases of the above three species following gap formation. Differences in response to canopy gaps suggest differences in how these species ascend to the canopy strata. T. plicata may be less dependent on gaps to reach the canopy. Differing strategies for ascending to the canopy strata may be important in facilitating coexistence of these three species in old‐growth forests of coastal British Columbia.     

Issues in stem cell plasticity

Experimental biology and medicine work with stem cells more than twenty years. The method discovered for in vitro culture of human embryonal stem cells acquired at abortions or from?surplus” embryos left from in vitro fertilization, evoked immediately ideas on the posibility to aim development and differentiation of these cells at regeneration of damaged tissues. Recently, several surprising observations proved that even tissue‐specific (multipotent) stem cells are capable, under suitable conditions of producing a while spectrum of cell types, regardless, whether these tissues are derived from the same germ layer or not. This ability is frequently called stem cell plasticity but other authors also use different names ‐?non‐orthodox differentiation” or?transdifferentiation”. In this paper we wish to raise several important questions and problems related to this theme. Let us remind some of them: Is it possible to force cells of one‐type tissue to lool and act as cells of another tissue? Are these changes netural? Could these trans‐formations be used to treat diseases? What about the bioethic issue? However, the most serious task “still remains to be soloved ‐ how to detect, harvestand culture stem cells for therapy of certain diseases”.     

Pathogen recognition and signal transduction by the Pto kinase

In tomato, the disease resistance genePto confers resistance to bacterial speck disease by recognizing the expression of a corresponding avirulence gene,avrPto, in the pathogenPseudomonas syringae pv.tomato (Martinet al. 1993). Similar “gene-for-gene” interactions occur in many plant-pathogen associations (Flor 1971). Such recognition events often lead to the activation in the plant of a variety of defense responses including a rapid induction of localized necrosis at the site of infection (the hypersensitive response, HR), increased expression of defense-related genes, production of antimicrobial compounds, lignin formation, and the oxidative burst (Lambet al. 1989, Mehdy 1994). As a result, the pathogen is contained at the infection site and its growth is inhibited.Pto encodes a serine/threonine protein kinase and belongs to a clustered multigene family. Another member of thePto family calledFen confers no known disease resistance, but mediates a hypersensitive-like reaction in the plant to the insecticide fenthion (Martinet al. 1994). We are interested in a number of fundamental questions concerning the Pto signaling pathways. What is the molecular basis of thePto-avrPto gene-for-gene interaction? What are the components involved in thePto-mediated signal transduction chain? How does thePto kinase activate complex defense responses? This paper summarizes our recent progress towards understanding these questions.     

Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We Forget the Fathers?

What are the effects of our environment on human development and the next generation? Numerous studies have provided ample evidence that a healthy environment and lifestyle of the mother is important for her offspring. Biological mechanisms underlying these environmental influences have been proposed to involve alterations in the epigenome. Is there enough evidence to suggest a similar contribution from the part of the father? Animal models provide proof of a transgenerational epigenetic effect through the paternal germ line, but can this be translated to humans? To date, literature on fathers is scarce. Human studies do not always incorporate appropriate tools to evaluate paternal influences or epigenetic effects. In reviewing the literature, I stress the need to explore and recognize paternal contributions to offspring's health within the Developmental Origins of Health and Disease hypothesis, and coin this new concept the Paternal Origins of Health and Disease paradigm (POHaD). A better understanding of preconceptional origins of disease through the totality of paternal exposures, or the paternal exposome, will provide evidence‐based public health recommendations for future fathers.

     

Molecular clocks underlying vertebrate embryo segmentation: A 10-year-old hairy-go-round

Segmentation of the vertebrate embryo body is a fundamental developmental process that occurs with strict temporal precision. Temporal control of this process is achieved through molecular segmentation clocks, evidenced by oscillations of gene expression in the unsegmented presomitic mesoderm (PSM, precursor tissue of the axial skeleton) and in the distal limb mesenchyme (limb chondrogenic precursor cells). The first segmentation clock gene, hairy1, was identified in the chick embryo PSM in 1997. Ten years later, chick hairy2 expression unveils a molecular clock operating during limb development. This review revisits vertebrate embryo segmentation with special emphasis on the current knowledge on somitogenesis and limb molecular clocks. A compilation of human congenital disorders that may arise from deregulated embryo clock mechanisms is presented here, in an attempt to reconcile different sources of information regarding vertebrate embryo development. Challenging open questions concerning the somitogenesis clock are presented and discussed, such as When?, Where?, How?, and What for? Hopefully the next decade will be equally rich in answers. Birth Defects Research (Part C) 81:65–83, 2007. © 2007 Wiley‐Liss, Inc.     

From remotely sensed solar-induced chlorophyll fluorescence to ecosystem structure,function, and service: Part I—Harnessing theory

Solar-induced chlorophyll fluorescence (SIF) is a remotely sensed optical signal emitted during the light reactions of photosynthesis. The past two decades have witnessed an explosion in availability of SIF data at increasingly higher spatial and temporal resolutions, sparking applications in diverse research sectors (e.g., ecology, agriculture, hydrology, climate, and socioeconomics). These applications must deal with complexities caused by tremendous variations in scale and the impacts of interacting and superimposing plant physiology and three-dimensional vegetation structure on the emission and scattering of SIF. At present, these complexities have not been overcome. To advance future research, the two companion reviews aim to (1) develop an analytical framework for inferring terrestrial vegetation structures and function that are tied to SIF emission, (2) synthesize progress and identify challenges in SIF research via the lens of multi-sector applications, and (3) map out actionable solutions to tackle these challenges and offer our vision for research priorities over the next 5–10 years based on the proposed analytical framework. This paper is the first of the two companion reviews, and theory oriented. It introduces a theoretically rigorous yet practically applicable analytical framework. Guided by this framework, we offer theoretical perspectives on three overarching questions: (1) The forward (mechanism) question—How are the dynamics of SIF affected by terrestrial ecosystem structure and function? (2) The inference question: What aspects of terrestrial ecosystem structure, function, and service can be reliably inferred from remotely sensed SIF and how? (3) The innovation question: What innovations are needed to realize the full potential of SIF remote sensing for real-world applications under climate change? The analytical framework elucidates that process complexity must be appreciated in inferring ecosystem structure and function from the observed SIF; this framework can serve as a diagnosis and inference tool for versatile applications across diverse spatial and temporal scales.