The need for speed

DNA sequence data are being produced at an ever-increasing rate. The Bowtie sequence-alignment algorithm uses advanced data structures to help data analysis keep pace with data generation.     

The need for speed. II. Myelin in calanoid copepods

Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group. Accepted: 8 January 2000     

A viral sampling design for testing the molecular clock and for estimating evolutionary rates and divergence times

MOTIVATION: The high pace of viral sequence change means that variation in the times at which sequences are sampled can have a profound effect both on the ability to detect trends over time in evolutionary rates and on the power to reject the Molecular Clock Hypothesis (MCH). Trends in viral evolutionary rates are of particular interest because their detection may allow connections to be established between a patient's treatment or condition and the process of evolution. Variation in sequence isolation times also impacts the uncertainty associated with estimates of divergence times and evolutionary rates. Variation in isolation times can be intentionally adjusted to increase the power of hypothesis tests and to reduce the uncertainty of evolutionary parameter estimates, but this fact has received little previous attention. RESULTS: We provide approximations for the power to reject the MCH when the alternative is that rates change in a linear fashion over time and when the alternative is that rates differ randomly among branches. In addition, we approximate the standard deviation of estimated evolutionary rates and divergence times. We illustrate how these approximations can be exploited to determine which viral sample to sequence when samples representing different dates are available.     

Marine reserves: the need for systems

Highly protected marine reserves are areas of the sea in which human disturbances are minimised so that the full natural biological diversity is maintained or, more often, allowed to recover to a more natural state. Europe has very few marine reserves; they are very small and almost all are in the Mediterranean. There are at present no official plans to create effective systems of marine reserves. Europe has many so-called Marine Protected Areas (MPAs). These are marine areas with some extra regulations or planning procedures. MPAs aim to make human activities more efficient and more sustainable. MPAs are user-orientated, knowledge-based, locality-dependent, problem-solving extensions of standard marine planning and management. Marine reserves are quite different. All extractive and potentially disturbing human activities are prohibited. The burden of proof is reversed; no evidence of damage or danger to particular species or habitats is required; all marine life is protected on principle. The concept of marine reserves is simple and practical, but because it is new, different and additional to existing marine management, the idea is seen by many as revolutionary. Basic biological principles and practical experience in many countries make it clear that marine reserves are important to science and education, essential for conservation and useful in resource management. These features apply in all regions and ecosystems. They are independent of climate, biogeography, current human activities and the present management. Representative and viable systems of marine reserves are needed in all regions. Fishing and other human disturbances have been widespread and intensive for so long that it is very difficult to predict the stages of recovery that occur in marine reserves. Furthermore, while some features change rapidly (e.g. numbers of previously targeted species), recovery continues for a long time (e.g. fourth- and fifth-order trophic and structural changes after >25 years). None of this alters the fact that, in scientific terms, marine reserves are controls not manipulations. Such controls are required if scientists are to understand the intrinsic processes and obtain data that are not confounded by human activities (e.g. separating natural variation from fishing effects). No significant progress will be made to establish marine reserves in Europe until scientists speak out strongly and clearly on the issue. We consider it is part of our professional duty as marine biologists to state publicly and frequently the need for a representative, replicated, networked and sustainable system of highly protected marine reserves. We doubt if our grandchildren will accept any excuses if we fail. Guest editors: J. Davenport, G. Burnell, T. Cross, M. Emmerson, R. McAllen, R. Ramsay & E. Rogan Challenges to Marine Ecosystems     

The need for anonymous genetic counseling and testing.

Concerns are mounting about the risks of genetic discrimination resulting from the release of predictive and presymptomatic genetic test results to employers, insurers, and others. The ability to keep this information confidential is questionable, particularly in view of the expansion of electronic medical databases. One solution is to afford individuals access to anonymous genetic counseling and testing. Probands would be identified only by a code that would not reveal personal information, and test results would be stored, retrieved, and released solely on the basis of this code. The experience with anonymous HIV testing, while not completely analogous, suggests that such an approach would be both practical and effective.     

The relation between maximal running speed and body mass in terrestrial mammals

The available data on maximal running speeds of mammals are presented, and the relationship between speed and body mass is considered. For all mammals ( n = 106), maximal running speed scales as (body mass)^0–17; however, the largest mammals are not the fastest, and an optimal size with regards to running ability is suggested ( 119 kg). Maximal running speeds are, on the average, somewhat more than twice maximal aerobic speeds.
Within the Artiodactyla, Carnivora or Rodentia, maximal running speed is mass independent, in agreement with theoretical expectations for geometrically similar animals (Thompson, 1917; Hill, 1950). McMahon's (1975 b ) model for elastic similarity is therefore not supported by the available data on maximal running speeds, and there appears to be no necessary correspondence between scaling of limb bone proportions and running ability.     

The need for a formal invalidation process for animal and non-animal tests

A plethora of regulations require that many chemicals and chemical products are tested for efficacy and/or toxicity. When permitted to operate effectively and without bias, the ECVAM/ICCVAM/OECD validation process can be used to independently establish that new animal and non-animal test procedures are sufficiently relevant and reliable for their stated purposes and should be considered for regulatory use. However, the validation process is under threat because of vested interests of various kinds, and it is clear that many currently-accepted animal tests and candidate animal and non-animal tests do not, and could never, meet the agreed criteria for necessity, test development, prevalidation, validation and acceptance. We therefore need an invalidation process to parallel and protect the validation process, so that such methods could be independently reviewed and declared irrelevant and/or unreliable for their claimed purposes. An additional advantage of such a process would be that valuable resources would no longer be wasted in attempts to secure the acceptance of inherently inadequate tests.     

Codon equilibrium II: Its use in estimating silent-substitution rates

Summary We study the equilibrium in the use of synonymous codons by eukaryotic organisms and find five equations involving substitution rates that we believe embody the important implications of equilibrium for the process of silent substitution. We then combine these five equations with additional criteria to determine sets of substitution rates applicable to eukaryotic organisms. One method employs the equilibrium equations and a principle of maximum entropy to find the most uniform set of rates consistent with equilibrium. In a second method we combine the equilibrium equations with data on the man-mouse divergence to determine that set of rates that is most neutral yet consistent with both types of data (i.e., equilibrium and divergence data). Simulations show this second method to be quite reliable in spite of significant saturation in the substitution process. We find that when divergence data are included in the calculation of rates, even though these rates are chosen to be as neutral as possible, the strength of selection inferred from the nonuniformity of the rates is approximately doubled. Both sets of rates are applied to estimate the human-mouse divergence time based on several independent subsets of the divergence data consisting of the quartet, C- or T-ending duet, and A- or G-ending duet codon sets. Both rate sets produce patterns of divergence times that are shortest for the quartet data, intermediate for the CT-ending duets, and longest for the AG-ending duets. This indicates that rates of transitions in the duet-codon sets are significantly higher than those in the quartet-codon sets; this effect is especially marked for AG, the rate of which in duets must be about double that in quartets.     

Codon equilibrium II: Its use in estimating silent-substitution rates

We study the equilibrium in the use of synonymous codons by eukaryotic organisms and find five equations involving substitution rates that we believe embody the important implications of equilibrium for the process of silent substitution. We then combine these five equations with additional criteria to determine sets of substitution rates applicable to eukaryotic organisms. One method employs the equilibrium equations and a principle of maximum entropy to find the most uniform set of rates consistent with equilibrium. In a second method we combine the equilibrium equations with data on the man-mouse divergence to determine that set of rates that is most neutral yet consistent with both types of data (i.e., equilibrium and divergence data). Simulations show this second method to be quite reliable in spite of significant saturation in the substitution process. We find that when divergence data are included in the calculation of rates, even though these rates are chosen to be as neutral as possible, the strength of selection inferred from the nonuniformity of the rates is approximately doubled. Both sets of rates are applied to estimate the human-mouse divergence time based on several independent subsets of the divergence data consisting of the quartet, C- or T-ending duet, and A- or G-ending duet codon sets. Both rate sets produce patterns of divergence times that are shortest for the quartet data, intermediate for the CT-ending duets, and longest for the AG-ending duets. This indicates that rates of transitions in the duet-codon sets are significantly higher than those in the quartet-codon sets; this effect is especially marked for A----G, the rate of which in duets must be about double that in quartets.     

The need for speed. I. Fast reactions and myelinated axons in copepods

A rapid and powerful escape response decreases predation risk in planktonic copepods. Calanoid copepods are sensitive to small and brief hydrodynamic disturbances: they respond with multiple nerve impulses to a vibrating sphere. Some species, such as Pleuromamma xiphias and Labidocera madurae, respond with very large spikes (1–4 mV), whereas maximum spike heights are an order of magnitude smaller in others, such as Undinula vulgaris and Neocalanus gracilis. A comparative study of the escape responses showed that all species reacted within 10 ms of the initiation of a hydrodynamic stimulus. However, U. vulgaris and N. gracilis had significantly shorter reaction times (minimum reaction times: 1.5 ms and 1.6 ms) than the other two, P. xiphias (6.6 ms) and L. madurae (3.1 ms). Examination of the first antenna and the central nervous system using transmission electron microscopy revealed extensive myelination of sensory and motor axons in the two species with the shorter reaction times. Axons of the other two species resembled typical crustacean unmyelinated fibers. A survey of 20 calanoids revealed that none of the species in two of the more ancient superfamilies possessed myelin, but myelination was present in the species from three more recently-evolved superfamilies. Accepted: 8 January 2000     

MareyMap: an R-based tool with graphical interface for estimating recombination rates

Comparing genetic and physical maps (the so-called Marey map approach) is still the most widely used approach to estimate genome-wide recombination rates. Remarkably, there is no available bioinformatics tool specifically devoted to Marey map approach. Here, we developed such a tool called MareyMap based on GNU R and Tcl/Tk. MareyMap offers a user-friendly graphical interface and includes useful features, such as data cleaning process, sophisticated interpolation methods to estimate local rates, possibility of complex queries, various range of import-export files. Moreover, MareyMap comes with ready-to-use maps for human, Drosophila, Caenorhabditis elegans and Arabidopsis. MareyMap has been made so that it can be easily upgraded with new data and interpolation methods. Availability: http://pbil.univ-lyon1.fr/software/mareymap/.