Regional effect on the molecular clock rate of protein evolution in Eutherian and Metatherian genomes

Background Different types of proteins diverge at vastly different rates. Moreover, the same type of protein has been observed to evolve with different rates in different phylogenetic lineages. In the present study we measured the rates of protein evolution in Eutheria (placental mammals) and Metatheria (marsupials) on a genome-wide basis and we propose that the gene position in the genome landscape has an important influence on the rate of protein divergence. Results We analyzed a protein-encoding gene set (n = 15,727) common to 16 mammals (12 Eutheria and 4 Metatheria). Using sliding windows that averaged regional effects of protein divergence we constructed landscapes in which strong and lineage-specific regional effects were seen on the molecular clock rate of protein divergence. Within each lineage, the relatively high rates were preferentially found in subtelomeric chromosomal regions. Such regions were observed to contain important and well-studied loci for fetal growth, uterine function and the generation of diversity in the adaptive repertoire of immunoglobulins. Conclusions A genome landscape approach visualizes lineage-specific regional differences between Eutherian and Metatherian rates of protein evolution. This phenomenon of chromosomal position is a new element that explains at least part of the lineage-specific effects and differences between proteins on the molecular clock rates.

Characterization and hierarchical static timing analysis of mixed-signal design

As the technology grows, the tendency to increase the data rate also increases. Clocks with higher frequencies have to be generated to meet the increased data rate. Any mismatch between the clock rate and data rate will lead to the capture of the wrong data. Hence performing timing analysis for any design to validate the capture of correct data plays a major role in any System on chip. This paper explains the procedure followed to perform timing analysis for any mixed-signal design.

Compensation of time-varying clock-offset in a LBL navigation

This paper presents compensation of the clock-offset in a long baseline (LBL)navigation. It departs from the existing literature mainly in dealing with a time-varyingclock-offset, i.e. the clock-rate drifts over the time. Specifically, the clock-offsetdynamics are introduced to the ToFs as an autoregressive filter.Subsequently,interactions among the now biased ToFs and the kinematics of an autonomousunderwater vehicle (AUV)–the navigation subject–are represented in a state-spaceform. Implementing the so-called graphic approach, minimum sensor requirementfor this system’s observability is then explicated. Finally, a standard discrete Kalmanfilter is deployed as the state estimator. By simulation, it is demonstrated that theestimator manages to compensate the offset and to provide localization with less than1 m accuracy

Additive Uncorrelated Relaxed Clock Models for the Dating of Genomic Epidemiology Phylogenies

Phylogenetic dating is one of the most powerful and commonly used methods of drawing epidemiological interpretations from pathogen genomic data. Building such trees requires considering a molecular clock model which represents the rate at which substitutions accumulate on genomes. When the molecular clock rate is constant throughout the tree then the clock is said to be strict, but this is often not an acceptable assumption. Alternatively, relaxed clock models consider variations in the clock rate, often based on a distribution of rates for each branch. However, we show here that the distributions of rates across branches in commonly used relaxed clock models are incompatible with the biological expectation that the sum of the numbers of substitutions on two neighboring branches should be distributed as the substitution number on a single branch of equivalent length. We call this expectation the additivity property. We further show how assumptions of commonly used relaxed clock models can lead to estimates of evolutionary rates and dates with low precision and biased confidence intervals. We therefore propose a new additive relaxed clock model where the additivity property is satisfied. We illustrate the use of our new additive relaxed clock model on a range of simulated and real data sets, and we show that using this new model leads to more accurate estimates of mean evolutionary rates and ancestral dates.

Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses

BackgroundThe emergence and spread of tick-borne arboviruses pose an increased challenge to human and animal health. In Europe this is demonstrated by the increasingly wide distribution of tick-borne encephalitis virus (TBEV, Flavivirus, Flaviviridae), which has recently been found in the UK. However, much less is known about other tick-borne flaviviruses (TBFV), such as the closely related louping ill virus (LIV), an animal pathogen which is endemic to the UK and Ireland but which has been detected in other parts of Europe including Scandinavia and Russia. The emergence and potential spatial overlap of these viruses necessitates improved understanding of LIV genomic diversity, geographic spread and evolutionary history.Methodology/principal findingsWe sequenced a virus archive composed of 22 LIV isolates which had been sampled throughout the UK over a period of over 80 years. Combining this dataset with published virus sequences, we detected no sign of recombination and found low diversity and limited evidence for positive selection in the LIV genome. Phylogenetic analysis provided evidence of geographic clustering as well as long-distance movement, including movement events that appear recent. However, despite genomic data and an 80-year time span, we found that the data contained insufficient temporal signal to reliably estimate a molecular clock rate for LIV. Additional analyses revealed that this also applied to TBEV, albeit to a lesser extent, pointing to a general problem with phylogenetic dating for TBFV.Conclusions/significanceThe 22 LIV genomes generated during this study provide a more reliable LIV phylogeny, improving our knowledge of the evolution of tick-borne flaviviruses. Our inability to estimate a molecular clock rate for both LIV and TBEV suggests that temporal calibration of tick-borne flavivirus evolution should be interpreted with caution and highlight a unique aspect of these viruses which may be explained by their reliance on tick vectors.Author SummaryTick-borne pathogens represent a major emerging threat to public health and in recent years have been expanding into new areas. LIV is a neglected virus endemic to the UK and Ireland (though it has been detected in Scandinavia and Russia) which is closely related to the major human pathogen TBEV, but predominantly causes disease in sheep and grouse. The recent detection of TBEV in the UK, which has also emerged elsewhere in Europe, requires more detailed understanding of the spread and sequence diversity of LIV. This could be important for diagnosis and vaccination, but also to improve our understanding of the evolution and emergence of these tick-borne viruses. Here we describe the sequencing of 22 LIV isolates which have been sampled from several host species across the past century. We have utilised this dataset to investigate the evolutionary pressures that LIV is subjected to and have explored the evolution of LIV using phylogenetic analysis. Crucially we were unable to estimate a reliable molecular clock rate for LIV and found that this problem also extends to a larger phylogeny of TBEV sequences. This work highlights a previously unknown caveat of tick-borne flavivirus evolutionary analysis which may be important for understanding the evolution of these important pathogens.

A Fast Approach for Generating Efficient Parsers on FPGAs

The development of modern networking requires that high-performance network processors be designed quickly and efficiently to support new protocols. As a very important part of the processor, the parser parses the headers of the packets—this is the precondition for further processing and finally forwarding these packets. This paper presents a framework designed to transform P4 programs to VHDL and to generate parsers on Field Programmable Gate Arrays (FPGAs). The framework includes a pipeline-based hardware architecture and a back-end compiler. The hardware architecture comprises many components with varying functionality, each of which has its own optimized VHDL template. By using the output of a standard frontend P4 compiler, our proposed compiler extracts the parameters and relationships from within the used components, which can then be mapped to corresponding templates by configuring, optimizing, and instantiating them. Finally, these templates are connected to output VHDL code. When a prototype of this framework is implemented and evaluated, the results demonstrate that the throughputs of the generated parsers achieve nearly 320 Gbps at a clock rate of around 300 MHz. Compared with state-of-the-art solutions, our proposed parsers achieve an average of twice the throughput when similar amounts of resources are being used.

Analysis and Design of Universal Shift Register Using Pulsed Latches

Power utilization and die region space are the significant boundaries which are considered for structuring low level power outcomes. This paper put forward the structure of low force general move register and 4-piece counter utilizing pipe rationale. Since flip failures are an innate structure hinder in a few applications, different flip lemon are over viewed and executed in widespread move register and 4-piece counter. Flip lemon utilizing pipe rationale is viewed as dependent on the correlation of intensity and region. At last, a low force all inclusive move register and 4-piece counter is planned utilizing pipe rationale. The proposed USR and 4-piece counters are mimicked with various clock rate going from 100 KHz to 500MHz. Re-enactment of these flip flounders, the widespread move register and the 4-piece counters are finished utilizing Tanner device at 180nm innovation. The normal force and the PDP of USR are improved by 33% and 27% and further the normal force and the PDP of 4-piece counter are improved by 36.9% and 30.2% when contrasted and existing plan separately. So the put forward plan is reasonable for low level power and elite applications.