Can we find the genes involved in complex traits?

A report on the third Complex Trait Consortium meeting, Bar Harbor, USA, 6-9 July 2004.     

Natural variation in phosphorylation of photosystem II proteins in Arabidopsis thaliana: is it caused by genetic variation in the STN kinases?

Reversible phosphorylation of photosystem II (PSII) proteins is an important regulatory mechanism that can protect plants from changes in ambient light intensity and quality. We hypothesized that there is natural variation in this process in Arabidopsis (Arabidopsis thaliana), and that this results from genetic variation in the STN7 and STN8 kinase genes. To test this, Arabidopsis accessions of diverse geographical origins were exposed to two light regimes, and the levels of phospho-D1 and phospho-light harvesting complex II (LHCII) proteins were quantified by western blotting with anti-phosphothreonine antibodies. Accessions were classified as having high, moderate or low phosphorylation relative to Col-0. This variation could not be explained by the abundance of the substrates in thylakoid membranes. In genotypes with atrazine-resistant forms of the D1 protein, low D1 and LHCII protein phosphorylation was observed, which may be due to low PSII efficiency, resulting in reduced activation of the STN kinases. In the remaining genotypes, phospho-D1 levels correlated with STN8 protein abundance in high-light conditions. In growth light, D1 and LHCII phosphorylation correlated with longitude and in the case of LHCII phosphorylation also with temperature variability. This suggests a possible role of natural variation in PSII protein phosphorylation in the adaptation of Arabidopsis to diverse environments.     

How do goannas find sea turtle nests?

Squamate reptiles rely heavily on visual and chemical cues to detect their prey, so we expected yellow‐spotted goannas (Varanus panoptes) which are predators of sea turtle nests on mainland beaches in northern Australia would use these cues to find sea turtle nests. Ghost crabs (Ocypode ceratophthalmus and Ocypode cordimanus) are also common on Australian sea turtle nesting beaches and frequently burrow into sea turtle nests. However, the potential for ghost crab burrowing activity at sea turtle nests to signal the location of a nest to goannas has not been investigated. Here, we used camera traps and presence of tracks at nests to record goanna activity around selected nests during the incubation period and 10 days after hatchling turtles emerged from their nests. We also recorded the number of ghost crab burrows around nests to evaluate ghost crab activity. Our results indicated that nest discovery by goannas was independent of nest age, but that the nest visitation rate of goannas and crabs increased significantly after a nest had been opened by a goanna or after hatchlings had emerged from the nest. There was no apparent connection between ghost crab burrows into a nest and the likelihood of that nest being predated by goannas.     

How well do we understand the clusters found in microarray data?

We wished to quantify the state-of-the-art of our understanding of clusters in microarray data. To do this we systematically compared the clusters produced on sets of microarray data using a representative set of clustering algorithms (hierarchical, k-means, and a modified version of QT_CLUST) with the annotation schemes MIPS, GeneOntology and GenProtEC. We assumed that if a cluster reflected known biology its members would share related ontological annotations. This assumption is the basis of "guilt-by-association" and is commonly used to assign the putative function of proteins. To statistically measure the relationship between cluster and annotation we developed a new predictive discriminatory measure. We found that the clusters found in microarray data do not in general agree with functional annotation classes. Although many statistically significant relationships can be found, the majority of clusters are not related to known biology (as described in annotation ontologies). This implies that use of guilt-by-association is not supported by annotation ontologies. Depending on the estimate of the amount of noise in the data, our results suggest that bioinformatics has only codified a small proportion of the biological knowledge required to understand microarray data.     

Food security in 2044: How do we control the fungal threat?

Plant fungal pathogens place considerable strain on agricultural productivity and threaten global food security. In recent decades, advances in crop breeding, farming practice and the agrochemical industry have allowed crop yields to keep pace with food demand. In this opinion article, we speculate on which recent technological advances will allow us to maintain this situation into the future. We take inspiration that it is 25 y since the first plant disease resistance genes were cloned, and imagine if and how agricultural control of pathogens will be achieved by the year 2044. We examine which technologies are best poised to make the jump from lab bench to field application, and propose that future control measures will likely depend on effective integrated disease management.     

How do site-specific DNA-binding proteins find their targets?

Essentially all the biological functions of DNA depend on site-specific DNA-binding proteins finding their targets, and therefore ‘searching’ through megabases of non-target DNA. In this article, we review current understanding of how this sequence searching is done. We review how simple diffusion through solution may be unable to account for the rapid rates of association observed in experiments on some model systems, primarily the Lac repressor. We then present a simplified version of the ‘facilitated diffusion’ model of Berg, Winter and von Hippel, showing how non-specific DNA–protein interactions may account for accelerated targeting, by permitting the protein to sample many binding sites per DNA encounter. We discuss the 1-dimensional ‘sliding’ motion of protein along non-specific DNA, often proposed to be the mechanism of this multiple site sampling, and we discuss the role of short-range diffusive ‘hopping’ motions. We then derive the optimal range of sliding for a few physical situations, including simple models of chromosomes in vivo, showing that a sliding range of ~100 bp before dissociation optimizes targeting in vivo. Going beyond first-order binding kinetics, we discuss how processivity, the interaction of a protein with two or more targets on the same DNA, can reveal the extent of sliding and we review recent experiments studying processivity using the restriction enzyme EcoRV. Finally, we discuss how single molecule techniques might be used to study the dynamics of DNA site-specific targeting of proteins.     

How do follower reef fishes find nuclear fishes?

Among reef fishes, it is common for “follower” individuals to accompany “nuclear” species and to feed on prey uncovered by their foraging. In this study, I examine the cues used by followers to find nuclear fish. A model of a ubiquitous nuclear fish was maintained immobile or moved to disturb the substratum and the number of fish species and individuals attracted was compared to control treatments. The results showed that: 1) bottom disturbance was the strongest attraction factor for follower reef fishes; 2) visual features of the nuclear also attracted follower reef fishes; 3) there was no evidence of an interaction between bottom disturbance and nuclear fish appearance in the attraction of followers, supporting the idea that both factors independently elicit following behaviour by reef fishes.     

How do Arabidopsis Roots Differentiate Hydrotropism from Gravitropism?

Root hydrotropism is a response to moisture gradients, which is considered to be important for drought avoidance. Recent reevaluation of root hydrotropism has emphasised the dominating effect of root gravitropism on it. It has been suggested that amyloplast dynamics inside columella cells and auxin regulation play roles in this interacting mechanism, even though the existence of distinct pathways of two tropisms derived from different stimuli remained unclear. We have recently found two factors that separate the mechanism of hydrotropism from that of gravitropism in Arabidopsis seedling roots. One is the difference in the mode of auxin-mediated growth regulation between two tropisms, and the other is the identification of gene indispensable only for root hydrotropism. Here we summarize the recent progress on root hydrotropism research and discuss the remaining and emerging issues.Key Words: auxin, gravitropism, hydrotropism, root, MIZU-KUSSEI1 (MIZ1)     

Physician prescribing practices: What do we know? Where do we go? How do we get there?

Although drug prescribing is one of the most important components of medical care, little is known about how prescribing practices are determined and how they can be influenced. Enhancing the quality and effectiveness of drug prescribing requires research and better dissemination of information to physicians and other decision-makers. This requires a collaborative effort and a coordinated action plan. Participants at the Physician Prescribing Practices Workshop, held in Ottawa in October 1995, addressed issues and made recommendations in three areas: current knowledge and issues for research in the field of prescribing practices, and the capacity of Canadian databases to study these issues, strategies for disseminating and implementing knowledge and research findings to enhance the quality of prescribing; and the formation of a network to foster collaboration among stakeholders.     

How much do we know about the breeding biology of bird species in the world?

Knowledge on species’ breeding biology is the building blocks of avian life history theory. A review for the current status of the knowledge at a global scale is needed to highlight the priority for future research. We collected all available information on three critical nesting parameters (clutch size, incubation period and nestling period) for the close to 10 000 bird species in the world and identified taxonomic, geographic and habitat gaps in the distribution of knowledge on avian breeding biology. The results show that only one third of all extant species are well known regarding the three nesting parameters analyzed, while the rest are partly or poorly known. Most data deficient taxonomic groups are tropical forest nesters, particularly from the Amazon basin, southeast Asia, Equatorial Africa and Madagascar – the places that harbor the world's highest bird diversity. These knowledge gaps could be hampering our understanding of avian life histories. Ornithologists are encouraged to pay more efforts to explore the breeding biology of those poorly‐known species.     

How much do we know about the current extinction rate?

Since about J600, 486 animal species have been recorded extinct. This represents about 0.04% of all animal species so far described. In the same period, 600 plant species are known to have disappeared, about 0.25% of the total. These figures are much smaller than those of the Permian/ Triassic and Cretaceous/Tertiary mass extinctions. One might therefore conclude that at present life on earth is at comparatively little risk of extinction. However, there is a growing body of data to show that the converse is true.     

How many genes in Arabidopsis come from cyanobacteria? An estimate from 386 protein phylogenies

It is well known that chloroplasts and mitochondria donated many genes to nuclear chromosomes during evolution - but how many is "many"? A sample of 3961 Arabidopsis nuclear protein-coding genes was compared with the complete set of proteins from yeast and 17 reference prokaryotic genomes, including one cyanobacterium (the lineage from which plastids arose). The analysis of 386 phylogenetic trees distilled from these data suggests that between approximately 400 (1.6%) and approximately 2200 (9.2%) of Arabidopsis nuclear genes stem from cyanobacteria. The degree of conservation preserved in protein sequences in addition to lateral gene transfer between free-living prokaryotes pose substantial challenges to genome phylogenetics.     

How do flies tolerate microorganisms in the gut?

Although gut epithelia are in constant contact with a large number of microbe-derived immune elicitors such as peptidoglycan, they do not mount an intense immune response. In this issue of Cell Host & Microbe, Lhocine et al. (2008) report that the PIMS gene product induces immune tolerance by reducing the availability of the peptidoglycan receptor in the plasma membrane. These findings provide a novel insight into the molecular mechanisms by which the host gut maintains balanced host-microbe interactions.     

Invertebrates in the canopy of tropical rain forests How much do we really know?

The current state of knowledge of canopy invertebrates in tropical rain forests is reviewed using data drawn, without bias toward taxon, collecting method or biogeographical region, from 89 studies concerned with mass-collecting (>1000 individuals). The review is intended to identify the most serious gaps and biases in the distribution of higher taxa among forest types and biogeographical regions. With respect to knowledge, biogeographical regions can be ranked as Neotropical > Australian > Oriental > Afrotropical. The canopy of lowland wet and subtropical forests has been studied in greater detail, whereas the canopy of lowland dry and montane forests is much less well known. Collecting techniques influence greatly the present knowledge of canopy invertebrates. Invertebrates other than arthropods, often abundant in epiphytic habitats, phytotelmata and perched litter, are virtually unknown. The abundance of several groups, such as Acari, Collembola and Isoptera, is almost certainly seriously underestimated. Densities of invertebrate individuals in the canopy of tropical rain forests appear to be lower than in temperate forests, although invertebrate abundance is dissipated by the high standing-biomass of rain forests. Coleoptera, particularly Staphylinidae, Curculionidae and Chrysomelidae, along with Hymenoptera, Lepidoptera and Araneae appear to be the most speciose taxa in the canopy, and it is probable that this reflects their range of feeding habits and exploitation of rain forests habitats. The distribution of individuals among the major arthropod orders and across the studies examined is complex and depends on many factors. The amount of variance that can be directly explained by biogeography, forest types (subtropical, wet, dry or montane), or collecting methods appears to be about 11%. The explained variance increases when considering major families of Coleoptera (28%) or subfamilies of Chrysomelidae (40%). In all cases, the variance explained by the type of forest is much higher than by that explained by biogeography. These conclusions are similar when considering various prey-predator relationships in the canopy. This suggests that, at the higher taxa level, the composition of the invertebrate fauna in the canopy may vary comparatively more across forest types than across biogeographical regions and this is discussed briefly from a conservation viewpoint.