Evolutionary constraints on yeast protein size

BACKGROUND: Despite a strong evolutionary pressure to reduce genome size, proteins vary in length over a surprisingly wide range also in very compact genomes. Here we investigated the evolutionary forces that act on protein size in the yeast Saccharomyces cerevisiae utilizing a system-wide bioinformatics approach. Data on yeast protein size was compared to global experimental data on protein expression, phenotypic pleiotropy, protein-protein interactions, protein evolutionary rate and biochemical classification. RESULTS: Comparing the experimentally determined abundance of individual proteins, highly expressed proteins were found to be consistently smaller than lowly expressed proteins, in accordance with the biosynthetic cost minimization hypothesis. Yeast proteins able to maintain a high expression level despite a large size tended to belong to a very distinct set of protein families, notably nuclear transport and translation initiation/elongation. Large proteins have significantly more protein-protein interactions than small proteins, suggesting that a requirement for multiple interaction domains may constitute a positive selective pressure for large protein size in yeast. The higher frequency of protein-protein interactions in large proteins was not accompanied by a higher phenotypic pleiotropy. Hence, the increase in interactions may not reflect an increase in function differentiation. Proteins of different sizes also evolved at similar rates. Finally, whereas the biological process involved was found to have little influence on protein size the biochemical activity exerted by the protein represented a dominant factor. More than one third of all biochemical activity classes were enriched in one or more size intervals. CONCLUSION: In yeast, there is an inverse relationship between protein size and protein expression such that highly expressed proteins tend to be of smaller size. Also, protein size is moderately affected by protein connectivity and strongly affected by biochemical activity. Phenotypic pleiotropy does not seem to affect protein size

Contribution of type W human endogenous retroviruses to the human genome: Characterization of HERV-W proviral insertions and processed pseudogenes

Background: Human endogenous retroviruses (HERVs) are ancient sequences integrated in the germ line cells and vertically transmitted through the offspring constituting about 8% of our genome. In time, HERVs accumulated mutations that compromised their coding capacity. A prominent exception is HERV-W locus 7q21.2, producing a functional Env protein (Syncytin-1) coopted for placental syncytiotrophoblast formation. While expression of HERV-W sequences has been investigated for their correlation to disease, an exhaustive description of the group composition and characteristics is still not available and current HERV-W group information derive from studies published a few years ago that, of course, used the rough assemblies of the human genome available at that time. This hampers the comparison and correlation with current human genome assemblies. Results: In the present work we identified and described in detail the distribution and genetic composition of 213 HERV-W elements. The bioinformatics analysis led to the characterization of several previously unreported features and provided a phylogenetic classification of two main subgroups with different age and structural characteristics. New facts on HERV-W genomic context of insertion and co-localization with sequences putatively involved in disease development are also reported. Conclusions: The present work is a detailed overview of the HERV-W contribution to the human genome and provides a robust genetic background useful to clarify HERV-W role in pathologies with poorly understood etiology, representing, to our knowledge, the most complete and exhaustive HERV-W dataset up to date

CLIQ Based Quench Protection of 16 [T] Nb3Sn Block-Coil Dipole Magnets for a Future Circular Collider

Protection of large high-field, high-energy accelerator magnets is very challenging with current technology. To avoid damage to the magnet coil by local or global overheating, the maximum temperature in the hot-spot of the magnet coil must be kept under certain levels depending on the materials used in the coil construction. The current state of the art technology seems unable to do so. A novel protection system for large superconducting magnets based on generating Inter Filament Coupling Loss through current oscillations in the magnet circuit is applied and simulated successfully for the Nb3Sn block-coil dipole magnet intended for use in a 100 [TeV] Future Circular Collider. The proposed protection system is able to keep the maximum temperature of the magnet coil during a quench below 350 [K] at nominal operating conditions, system parameters and geometry, and is shown to achieve a maximum temperature in the coil hot-spot as low as 260 [K] for the optimal protection system configuration. Several variations on the nominal coil geometry have been investigated, showing that an increase in inductance is detrimental while a reduction is beneficial from the point of view of the new protection system. Among the variations investigated are a graded coil and a coil with a larger aperture than the nominal geometry. The graded coil is found the most difficult to protect, while the larger aperture coil variant is the easiest to protect, with regards to the hot-spot temperature. A large parameter space has been investigated, and the most influential parameters are found to alter the hot-spot temperature by 50 [K], while the least influential by 10 [K] when moving away from their respective nominal values. Most influential are the electrical configuration of the protection system, the non-Copper content of the superconducting strands and the coil geometry. Least influential are the residual resistivity ratio and filament twist pitch. Taking the internal voltages to ground in the coil during application of the new protection system into account, the graded coil must be discarded completely, as turn-to-turn voltages can reach several hundred volt. The reduced inductance variants, therein the larger aperture one, proves the optimal also with respect to voltage: the turn-to-turn voltages are kept well below 100 [V], while the inter-layer voltage, critical for the application of the new protection system, only barely exceeds 1 [kV]

CLIQ Based Quench Protection of 16 [T] Nb3Sn Block-Coil Dipole Magnets for a Future Circular Collider

Protection of large high-field, high-energy accelerator magnets is very challenging with current technology. To avoid damage to the magnet coil by local or global overheating, the maximum temperature in the hot-spot of the magnet coil must be kept under certain levels depending on the materials used in the coil construction. The current state of the art technology seems unable to do so. A novel protection system for large superconducting magnets based on generating Inter Filament Coupling Loss through current oscillations in the magnet circuit is applied and simulated successfully for the Nb3Sn block-coil dipole magnet intended for use in a 100 [TeV] Future Circular Collider. The proposed protection system is able to keep the maximum temperature of the magnet coil during a quench below 350 [K] at nominal operating conditions, system parameters and geometry, and is shown to achieve a maximum temperature in the coil hot-spot as low as 260 [K] for the optimal protection system configuration. Several variations on the nominal coil geometry have been investigated, showing that an increase in inductance is detrimental while a reduction is beneficial from the point of view of the new protection system. Among the variations investigated are a graded coil and a coil with a larger aperture than the nominal geometry. The graded coil is found the most difficult to protect, while the larger aperture coil variant is the easiest to protect, with regards to the hot-spot temperature. A large parameter space has been investigated, and the most influential parameters are found to alter the hot-spot temperature by 50 [K], while the least influential by 10 [K] when moving away from their respective nominal values. Most influential are the electrical configuration of the protection system, the non-Copper content of the superconducting strands and the coil geometry. Least influential are the residual resistivity ratio and filament twist pitch. Taking the internal voltages to ground in the coil during application of the new protection system into account, the graded coil must be discarded completely, as turn-to-turn voltages can reach several hundred volt. The reduced inductance variants, therein the larger aperture one, proves the optimal also with respect to voltage: the turn-to-turn voltages are kept well below 100 [V], while the inter-layer voltage, critical for the application of the new protection system, only barely exceeds 1 [kV]

PROPHECY—a database for high-resolution phenomics

The rapid recent evolution of the field phenomics—the genome-wide study of gene dispensability by quantitative analysis of phenotypes—has resulted in an increasing demand for new data analysis and visualization tools. Following the introduction of a novel approach for precise, genome-wide quantification of gene dispensability in Saccharomyces cerevisiae we here announce a public resource for mining, filtering and visualizing phenotypic data—the PROPHECY database. PROPHECY is designed to allow easy and flexible access to physiologically relevant quantitative data for the growth behaviour of mutant strains in the yeast deletion collection during conditions of environmental challenges. PROPHECY is publicly accessible at http://prophecy.lundberg.gu.se

No Definite Evidence for Human Endogenous Retroviral HERV-W and HERV-H RNAS in Plasma of Latvian Patients Suffering from Multiple Sclerosis and Other Neurological Diseases

Publisher Copyright: © 2016 by Jonas Blomberg.Multiple sclerosis (MS) is a neurological disease of unknown aetiology. Several research groups reported an increased level of human endogenous retroviruses HERV-W and HERV-H RNAs in cerebrospinal fluid, plasma and supernatants of cell cultures from MS individuals. To quantify the abundance of extracellular virion-associated HERV, RNAs in blood, plasma samples from Latvian MS patients, patients with other neurological diseases (OND), as well as blood donors (BD), were retrospectively studied by using both our previously published and newly developed quantitative Real-time reverse transcription PCR assays (QPCRs) targeting different polymerase (pol) gene regions of HERV-W and HERV-H. Unspecific signals due to incomplete removal of DNA were monitored by running the assays with and without reverse transcription (RT±) in parallel. According to our score, a few MS, OND and healthy controls gave borderline signals simultaneously with both newly developed HERV-H and HERV-W QPCRs, but the rest were negative. All borderline positive samples also had small amounts of non-retroviral cellular mRNA with possible origin from cell-free circulating RNA fragments, apoptotic bodies or exosomes, which can mimic the previously described virus-like particles. The results do not confirm the previous reports on prevalence of HERV-H or-W virion-associated RNA in plasma of MS patients.publishersversionPeer reviewe

Prevalence and Phylogeny of Coronaviruses in Wild Birds from the Bering Strait Area (Beringia)

Coronaviruses (CoVs) can cause mild to severe disease in humans and animals, their host range and environmental spread seem to have been largely underestimated, and they are currently being investigated for their potential medical relevance. Infectious bronchitis virus (IBV) belongs to gamma-coronaviruses and causes a costly respiratory viral disease in chickens. The role of wild birds in the epidemiology of IBV is poorly understood. In the present study, we examined 1,002 cloacal and faecal samples collected from 26 wild bird species in the Beringia area for the presence of CoVs, and then we performed statistical and phylogenetic analyses. We detected diverse CoVs by RT-PCR in wild birds in the Beringia area. Sequence analysis showed that the detected viruses are gamma-coronaviruses related to IBV. These findings suggest that wild birds are able to carry gamma-coronaviruses asymptomatically. We concluded that CoVs are widespread among wild birds in Beringia, and their geographic spread and frequency is higher than previously realised. Thus, Avian CoV can be efficiently disseminated over large distances and could be a genetic reservoir for future emerging pathogenic CoVs. Considering the great animal health and economic impact of IBV as well as the recent emergence of novel coronaviruses such as SARS-coronavirus, it is important to investigate the role of wildlife reservoirs in CoV infection biology and epidemiology

Characterization of Human MMTV-like (HML) Elements Similar to a Sequence That Was Highly Expressed in a Human Breast Cancer: Further Definition of the HML-6 Group

AbstractPreviously, we found a retroviral sequence, HML-6.2BC1,to be expressed at high levels in a multifocal ductal breast cancer from a 41-year-old woman who also developed ovarian carcinoma. The sequence of a human genomic clone (HML-6.28) selected by high-stringency hybridization with HML-6.2BC1is reported here. It was 99% identical to HML-6.2BC1and gave the same restriction fragments as total DNA. HML-6.28 is a 4.7-kb provirus with a 5′LTR, truncated in RT. Data from two similar genomic clones and sequences found in GenBank are also reported. Overlaps between them gave a rather complete picture of the HML-6.2BC1-like human endogenous retroviral elements. Work with somatic cell hybrids and FISH localized HML-6.28 to chromosome 6, band p21, close to the MHC region. The causal role of HML-6.28 in breast cancer remains unclear. Nevertheless, the ca. 20 Myr old HML-6 sequences enabled the definition of common and unique features of type A, B, and D (ABD) retroviruses. In Gag, HML-6 has no intervening sequences between matrix and capsid proteins, unlike extant exogenous ABD viruses, possibly an ancestral feature. Alignment of the dUTPase showed it to be present in all ABD viruses, but gave a phylogenetic tree different from trees made from other ABD genes, indicating a distinct phylogeny of dUTPase. A conserved 24-mer sequence in the amino terminus of some ABD envelope genes suggested a conserved function

Phylogeny-Directed Search for Murine Leukemia Virus-Like Retroviruses in Vertebrate Genomes and in Patients Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Prostate Cancer

Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV) like retroviruses (MLLVs) are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV) and Human Mouse retrovirus-like RetroViruses (HMRVs)) reported from patients suffering from prostate cancer (PC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect “stealth” infection, or that XMRV/HMRV never reached humans, have to be considered