A Blog Around The Clock

New and Exciting in PLoS this week

There are new articles in four PLoS journals today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week – you go and look for your own favourites:

Mammalian Sleep Dynamics: How Diverse Features Arise from a Common Physiological Framework:

The field of sleep physiology has made huge strides in recent years, uncovering the neurological structures which are critical to sleep regulation. However, given the small number of species studied in such detail in the laboratory, it remains to be seen how universal these mechanisms are across the whole mammalian order. Mammalian sleep is extremely diverse, and the unihemispheric sleep of dolphins is nothing like the rapidly cycling sleep of rodents, or the single daily block of humans. Here, we use a mathematical model to demonstrate that the established sleep physiology can indeed account for the sleep of a wide range of mammals. Furthermore, the model gives insight into why the sleep patterns of different species are so distinct: smaller animals burn energy more rapidly, resulting in more rapid sleep-wake cycling. We also show that mammals that sleep unihemispherically may have a single additional neuronal pathway which prevents sleep-promoting neurons on opposite sides of the hypothalamus from activating simultaneously. These findings suggest that the basic physiology controlling sleep evolved before mammals, and illustrate the functional flexibility of this simple system.

Evolutionary Trends of the Pharyngeal Dentition in Cypriniformes (Actinopterygii: Ostariophysi):

The fish order Cypriniformes is one of the most diverse ray-finned fish groups in the world with more than 3000 recognized species. Cypriniformes are characterized by a striking distribution of their dentition: namely the absence of oral teeth and presence of pharyngeal teeth on the last gill arch (fifth ceratobranchial). Despite this limited localisation, the diversity of tooth patterns in Cypriniformes is astonishing. Here we provide a further description of this diversity using X-ray microtomography and we map the resulting dental characters on a phylogenetic tree to explore evolutionary trends. We performed a pilot survey of dental formulae and individual tooth shapes in 34 adult species of Cypriniformes by X-ray microtomography (using either conventional X-ray machine, or synchrotron microtomography when necessary) or by dissecting. By mapping morphological results in a phylogenetic tree, it emerges that the two super-families Cobitoidea and Cyprinoidea have followed two distinct evolutionary pathways. Furthermore, our analysis supports the hypothesis of a three-row dentition as ancestral for Cyprinoidea and a general trend in tooth row reduction in most derived lineages. Yet, this general scheme must be considered with caution as several events of tooth row gain and loss have occurred during evolutionary history of Cyprinoidea. Dentition diversity in Cypriniformes constitutes an excellent model to study the evolution of complex morphological structures. This morphological survey clearly advocates for extending the use of X-ray microtomography to study tooth morphology in Cypriniformes. Yet, our survey also underlines that improved knowledge of Cypriniformes life traits, such as feeding habits, is required as current knowledge is not sufficient to conclude on the link between diet and dental morphology.

2010 ISCB Overton Prize Awarded to Steven E. Brenner:

Each year the International Society for Computational Biology (ISCB; http://www.iscb.org) honors a young scientist who has already achieved a significant and lasting impact on our field. The ISCB Awards Committee, comprised of current and former directors of the society and chaired by Søren Brunak, director of the Center for Biological Sequence Analysis at the Technical University of Denmark, has announced that the recipient of the 2010 ISCB Overton Prize is Steven E. Brenner of the University of California, Berkeley, California, United States (Image 1).

Plato’s Cave Algorithm: Inferring Functional Signaling Networks from Early Gene Expression Shadows:

Elucidating the biochemical interactions in living cells is essential to understanding their behavior under various external conditions. Some of these interactions occur between signaling components with many active states, and their activity levels may be difficult to measure directly. However, most methods to reverse engineer interaction networks rely on measuring gene activity at steady state under various cellular stimuli. Such gene measurements therefore ignore the intermediate effects of signaling components, and cannot reliably convey the interactions between the signaling components themselves. We propose using the changes in activity of early genes shortly after the stimulus to infer the functional interactions between the unmeasured signaling components. The change in expression in such genes at these times is directly and linearly affected by the signaling components, since there is insufficient time for other genes to be transcribed and interfere with the early genes’ expression. We present an algorithm that uses such measurements to reverse engineer the functional interaction network between signaling components, and also provides a means for testing these predictions. The algorithm therefore uses feasible experiments to reconstruct functional networks. We applied the algorithm to experimental measurements and uncovered known interactions, as well as novel interactions that were then confirmed experimentally.

OsPIE1, the Rice Ortholog of Arabidopsis PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1, Is Essential for Embryo Development:

The SWR1 complex is important for the deposition of histone variant H2A.Z into chromatin necessary to robustly regulate gene expression during growth and development. In Arabidopsis thaliana, the catalytic subunit of the SWR1-like complex, encoded by PIE1 (PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1), has been shown to function in multiple developmental processes including flowering time pathways and petal number regulation. However, the function of the PIE1 orthologs in monocots remains unknown. We report the identification of the rice (Oryza sativa) ortholog, OsPIE1. Although OsPIE1 does not exhibit a conserved exon/intron structure as Arabidopsis PIE1, its encoded protein is highly similar to PIE1, sharing 53.9% amino acid sequence identity. OsPIE1 also has a very similar expression pattern as PIE1. Furthermore, transgenic expression of OsPIE1 completely rescued both early flowering and extra petal number phenotypes of the Arabidopsis pie1-2 mutant. However, homozygous T-DNA insertional mutants of OsPIE1 in rice were embryonically lethal, in contrast to the viable mutants in the orthologous genes for yeast, Drosophila and Arabidopsis (Swr1, DOMINO and PIE1, respectively). Taken together, our results suggest that OsPIE1 is the rice ortholog of Arabidopsis PIE1 and plays an essential role in rice embryo development.

The Roots of Bioinformatics:

Every new scientific discipline or methodology reaches a point in its maturation where it is fruitful for it to turn its gaze inward, as well as backward. Such introspection helps to clarify the essential structure of a field of study, facilitating communication, pedagogy, standardization, and the like, while retrospection aids this process by accounting for its beginnings and underpinnings. In this spirit, PLoS Computational Biology is launching a new series of themed articles tracing the roots of bioinformatics. Essays from prominent workers in the field will relate how selected scientific, technological, economic, and even cultural threads came to influence the development of the field we know today. These are not intended to be review articles, nor personal reminiscences, but rather narratives from individual perspectives about the origins and foundations of bioinformatics, and are expected to provide both historical and technical insights. Ideally, these articles will offer an archival record of the field’s development, as well as a human face on an important segment of science, for the benefit of current and future workers.

Web-Based, Participant-Driven Studies Yield Novel Genetic Associations for Common Traits:

Twin studies have shown that many human physical characteristics, such as hair curl, earlobe shape, and pigmentation are at least partly heritable. In order to identify the genes involved in such traits, we administered Web-based surveys to the customer base of 23andMe, a personal genetics company. Upon completion of surveys, participants were able to see how their answers compared to those of other customers. Our examination of 22 different common traits in nearly 10,000 participants revealed associations among several single-nucleotide polymorphisms (SNPs, a type of common DNA sequence variation) and freckling, hair curl, asparagus anosmia (the inability to detect certain urinary metabolites produced after eating asparagus), and photic sneeze reflex (the tendency to sneeze when entering bright light). Additionally our analysis verified the association of a large number of previously identified genes with variation in hair color, eye color, and freckling. Our analysis not only identified new genetic associations, but also showed that our novel way of doing research–collecting self-reported data over the Web from involved participants who also receive interpretations of their genetic data–is a viable alternative to traditional methods.

Consent and Internet-Enabled Human Genomics:

This month, PLoS Genetics is publishing an article from the company 23andMe reporting the first genome-wide association studies (GWAS) on multiple traits ascertained by self-reported information provided through the Internet from over 10,000 participants who pay the company for providing whole genome genotypes [1]. The paper passed through scientific review by a panel of three experts relatively quickly and is sure to attract the attention of anyone with freckles, curly hair, or an aversion to asparagus. Novel associations are described for four intrinsically interesting traits (out of 22 considered), while known associations with hair and eye color are replicated in a dynamic data-gathering context. Additionally, intriguing observations on the interaction between genetic self-knowledge and self-report of phenotypes are described. The implications of the successful application of this Internet-enabled approach to GWAS research were considered to be more than sufficient to warrant publication in the journal. However, publication was delayed for six months while the editors sought a variety of opinions on three issues: ethical review, consent, and data access. Anyone who has read Rebecca Skloot’s The Immortal Life of Henrietta Lacks [2] will be sensitive to the ongoing ethical and moral concerns surrounding consent and research with human samples. The editors of PLoS Genetics decided to proceed after satisfying ourselves on two major points, namely that the participants were not coerced to participate in the study in any way, and they were clearly aware that their samples would be used for genetic research. Recognizing that institutional review is an imperfect process and that the complexities raised by GWAS are not readily resolved, we call for a concerted effort on the part of granting agencies, scientists, review boards, and the public communities they serve to standardize processes and procedures of consent and review of human genomic research. It also needs to be stated that the Editor-in-Chief, Professor Greg Barsh, is a potential consultant to 23andMe, and so recused himself from all dealings with this paper prior to acceptance.