Detecting Remote Sequence Homology in Disordered Proteins: Discovery of Conserved Motifs in the N-Termini of Mononegavirales phosphoproteins

Paramyxovirinae are a large group of viruses that includes measles virus and parainfluenza viruses. The viral Phosphoprotein (P) plays a central role in viral replication. It is composed of a highly variable, disordered N-terminus and a conserved C-terminus. A second viral protein alternatively expressed, the V protein, also contains the N-terminus of P, fused to a zinc finger. We suspected that, despite their high variability, the N-termini of P/V might all be homologous; however, using standard approaches, we could previously identify sequence conservation only in some Paramyxovirinae. We now compared the N-termini using sensitive sequence similarity search programs, able to detect residual similarities unnoticeable by conventional approaches. We discovered that all Paramyxovirinae share a short sequence motif in their first 40 amino acids, which we called soyuz1. Despite its short length (11–16aa), several arguments allow us to conclude that soyuz1 probably evolved by homologous descent, unlike linear motifs. Conservation across such evolutionary distances suggests that soyuz1 plays a crucial role and experimental data suggest that it binds the viral nucleoprotein to prevent its illegitimate self-assembly. In some Paramyxovirinae, the N-terminus of P/V contains a second motif, soyuz2, which might play a role in blocking interferon signaling. Finally, we discovered that the P of related Mononegavirales contain similarly overlooked motifs in their N-termini, and that their C-termini share a previously unnoticed structural similarity suggesting a common origin. Our results suggest several testable hypotheses regarding the replication of Mononegavirales and suggest that disordered regions with little overall sequence similarity, common in viral and eukaryotic proteins, might contain currently overlooked motifs (intermediate in length between linear motifs and disordered domains) that could be detected simply by comparing orthologous proteins

A management systems approach to rural development

Past failures to plan rural planning, planners' relative neglect of recurrent resource management, and the underutilised capacity of government field staff all support the case for increased attention to be given to management procedures in rural development. A simple systems presentation is used to set out a rural plan management system with six component systems: Programming and Implementation Management Field Staff Management Local Participation Procedures Evaluation Review Sequence Rural Research and Development Plan Formulation Procedures Management procedures for these six systems either have been or are being developed and tested in the Kenya Government's Special Rural Development Programme. They are described in turn. Choices and principles in system design and in replication both within Kenya and in other countries are discussed. The most important single conclusion is that public sector performance in rural development is most likely to be improved initially through attention to programming, implementation and monitoring, with later gradual extension through evaluation to plan formulation

PIM: a practical management system for implementing rural development programmes and projects

This paper describes the origins and operation of a management system for implementing rural development programmes and projects. The system has been developed from elements from several sources, including network analysis, Management by Objectives, and the Malaysian Red Book system. Simplifications have been continually introduced during testing. Independent evaluations of the system have found that it sharpens government implementation of projects and programmes in rural areas. The system has three main parts: an Annual Programming Exercise in which those responsible for implementation jointly plan how it shall be carried out; a Monthly Management Meeting which receives reports on progress and decides on who shall do what, how and by when; and a Monthly Management Report, distributed to those whose action is required, sent out shortly after the meeting. The system has operated in the Kenya Special Rural Development Programme for eighteen months. With minor adaptation it appears replicable within Kenya in connection with district planning. In Kenya and in other countries, it could be used to improve implementation of a wide variety of rural development programmes and projects. It might be particularly effective in Tanzania as a system for operation by the District Development Directors

Larger mammalian body size leads to lower retroviral activity

Retroviruses have been infecting mammals for at least 100 million years, leaving descendants in host genomes known as endogenous retroviruses (ERVs). The abundance of ERVs is partly determined by their mode of replication, but it has also been suggested that host life history traits could enhance or suppress their activity. We show that larger bodied species have lower levels of ERV activity by reconstructing the rate of ERV integration across 38 mammalian species. Body size explains 37% of the variance in ERV integration rate over the last 10 million years, controlling for the effect of confounding due to other life history traits. Furthermore, 68% of the variance in the mean age of ERVs per genome can also be explained by body size. These results indicate that body size limits the number of recently replicating ERVs due to their detrimental effects on their host. To comprehend the possible mechanistic links between body size and ERV integration we built a mathematical model, which shows that ERV abundance is favored by lower body size and higher horizontal transmission rates. We argue that because retroviral integration is tumorigenic, the negative correlation between body size and ERV numbers results from the necessity to reduce the risk of cancer, under the assumption that this risk scales positively with body size. Our model also fits the empirical observation that the lifetime risk of cancer is relatively invariant among mammals regardless of their body size, known as Peto's paradox, and indicates that larger bodied mammals may have evolved mechanisms to limit ERV activity

The Evolutionary History of Protein Domains Viewed by Species Phylogeny

Protein structural domains are evolutionary units whose relationships can be detected over long evolutionary distances. The evolutionary history of protein domains, including the origin of protein domains, the identification of domain loss, transfer, duplication and combination with other domains to form new proteins, and the formation of the entire protein domain repertoire, are of great interest.A methodology is presented for providing a parsimonious domain history based on gain, loss, vertical and horizontal transfer derived from the complete genomic domain assignments of 1015 organisms across the tree of life. When mapped to species trees the evolutionary history of domains and domain combinations is revealed, and the general evolutionary trend of domain and combination is analyzed.We show that this approach provides a powerful tool to study how new proteins and functions emerged and to study such processes as horizontal gene transfer among more distant species

Sex is always well worth its two-fold cost

Sex is considered as an evolutionary paradox, since its evolutionary advantage does not necessarily overcome the two fold cost of sharing half of one's offspring's genome with another member of the population. Here we demonstrate that sexual reproduction can be evolutionary stable even when its Darwinian fitness is twice as low when compared to the fitness of asexual mutants. We also show that more than two sexes are always evolutionary unstable. Our approach generalizes the evolutionary game theory to analyze species whose members are able to sense the sexual state of their conspecifics and to switch sexes consequently. The widespread emergence and maintenance of sex follows therefore from its co-evolution with even more widespread environmental sensing abilities.Comment: 8 pages, 3 figure

Overlapping genes and the proteins they encode differ significantly in their sequence composition from non-overlapping genes.

Overlapping genes represent a fascinating evolutionary puzzle, since they encode two functionally unrelated proteins from the same DNA sequence. They originate by a mechanism of overprinting, in which point mutations in an existing frame allow the expression (the "birth") of a completely new protein from a second frame. In viruses, in which overlapping genes are abundant, these new proteins often play a critical role in infection, yet they are frequently overlooked during genome annotation. This results in erroneous interpretation of mutational studies and in a significant waste of resources. Therefore, overlapping genes need to be correctly detected, especially since they are now thought to be abundant also in eukaryotes. Developing better detection methods and conducting systematic evolutionary studies require a large, reliable benchmark dataset of known cases. We thus assembled a high-quality dataset of 80 viral overlapping genes whose expression is experimentally proven. Many of them were not present in databases. We found that overall, overlapping genes differ significantly from non-overlapping genes in their nucleotide and amino acid composition. In particular, the proteins they encode are enriched in high-degeneracy amino acids and depleted in low-degeneracy ones, which may alleviate the evolutionary constraints acting on overlapping genes. Principal component analysis revealed that the vast majority of overlapping genes follow a similar composition bias, despite their heterogeneity in length and function. Six proven mammalian overlapping genes also followed this bias. We propose that this apparently near-universal composition bias may either favour the birth of overlapping genes, or/and result from selection pressure acting on them

The RNA Virus Database

The RNA Virus Database is a database and web application describing the genome organization and providing analytical tools for the 938 known species of RNA virus. It can identify submitted nucleotide sequences, can place them into multiple whole-genome alignments (in species where more than one isolate has been fully sequenced) and contains translated genome sequences for all species. It has been created for two main purposes: to facilitate the comparative analysis of RNA viruses and to become a hub for other, more specialised virus Web sites. It is available at the following four mirrored sites. http://virus.zoo.ox.ac.uk/rnavirusdb; http://hivweb.sanbi.ac.za/rnavirusdb; http://bioinf.cs.auckland.ac.nz/rnavirusdb; http://tree.bio.ed.ac.uk/rnavirusdb.Citation: Belshaw, R. et al. (2009). 'The RNA Virus Database', Nucleic Acids Research, 37(Database issue), D431-D435. [Available at http://nar.oxfordjournals.org/]. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited