Diana Ekman

What properties characterize the hub proteins of the protein-protein interaction network of Saccharomyces cerevisiae?

BackgroundMost proteins interact with only a few other proteins while a small number of proteins (hubs) have many interaction partners. Hub proteins and non-hub proteins differ in several respects; however, understanding is not complete about what properties characterize the hubs and set them apart from proteins of low connectivity. Therefore, we have investigated what differentiates hubs from non-hubs and static hubs (party hubs) from dynamic hubs (date hubs) in the protein-protein interaction network of Saccharomyces cerevisiae.ResultsThe many interactions of hub proteins can only partly be explained by bindings to similar proteins or domains. It is evident that domain repeats, which are associated with binding, are enriched in hubs. Moreover, there is an over representation of multi-domain proteins and long proteins among the hubs. In addition, there are clear differences between party hubs and date hubs. Fewer of the party hubs contain long disordered regions compared to date hubs, indicating that these regions are important for flexible binding but less so for static interactions. Furthermore, party hubs interact to a large extent with each other, supporting the idea of party hubs as the cores of highly clustered functional modules. In addition, hub proteins, and in particular party hubs, are more often ancient. Finally, the more recent paralogs of party hubs are underrepresented.ConclusionOur results indicate that multiple and repeated domains are enriched in hub proteins and, further, that long disordered regions, which are common in date hubs, are particularly important for flexible binding.

Expansion of Protein Domain Repeats

Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein–protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

Arrangements in the modular evolution of proteins

It has been known for the last couple of decades that proteins evolve partly through rearrangements of larger fragments, typically domains. These units are considered the basic modules of protein structure, evolution and function. In the last few years, the analysis of protein-domain rearrangements has provided us with functional and evolutionary insights and has aided improved functional predictions and domain assignments to previously uncharacterised genes and proteins. Although some mechanisms that govern modular rearrangements of protein domains have been uncovered, such as the addition or deletion of a single N- or C-terminal domain, much is still unknown about the genetics behind these arrangements.

Alcohol use among university students in Sweden measured by an electronic screening instrument

BackgroundElectronic-based alcohol screening and brief interventions for university students with problem drinking behaviours forms an important means by which to identify risky drinkers.MethodsIn this study an e-SBI project was implemented to assess drinking patterns, and to provide personalised feedback about alcohol consumption and related health problems, to students in a Swedish university. In this study, third semester university students (n = 2858) from all faculties (colleges) at the University were invited to participate in e-SBI screenings. This study employed a randomised controlled trial, with respondents having a equal chance of being assigned to a limited, or full-feedback response.ResultsThe study shows that high risk drinkers tend to underestimate their own consumption compared to others, and that these high risk drinkers experience more negative consequences after alcohol intake, than other respondents. There was a strong belief, for both high- and low-risk drinkers, that alcohol helped celebrations be more festive. This study also confirms findings from other study locations that while males drank more than females in our study population; females reached the same peak alcohol blood concentrations as males.ConclusionObtaining clear and current information on drinking patterns demonstrated by university students can help public health officials, university administration, and local health care providers develop appropriate prevention and treatment strategies.

Identifying and Quantifying Orphan Protein Sequences in Fungi

For large regions of many proteins, and even entire proteins, no homology to known domains or proteins can be detected. These sequences are often referred to as orphans. Surprisingly, it has been reported that the large number of orphans is sustained in spite of a rapid increase of available genomic sequences. However, it is believed that de novo creation of coding sequences is rare in comparison to mechanisms such as domain shuffling and gene duplication; hence, most sequences should have homologs in other genomes. To investigate this, the sequences of 19 complete fungi genomes were compared. By using the phylogenetic relationship between these genomes, we could identify potentially de novo created orphans in Saccharomyces cerevisiae. We found that only a small fraction, <2%, of the S. cerevisiae proteome is orphan, which confirms that de novo creation of coding sequences is indeed rare. Furthermore, we found it necessary to compare the most closely related species to distinguish between de novo created sequences and rapidly evolving sequences where homologs are present but cannot be detected. Next, the orphan proteins (OPs) and orphan domains (ODs) were characterized. First, it was observed that both OPs and ODs are short. In addition, at least some of the OPs have been shown to be functional in experimental assays, showing that they are not pseudogenes. Furthermore, in contrast to what has been reported before and what is seen for older orphans, S. cerevisiae specific ODs and proteins are not more disordered than other proteins. This might indicate that many of the older, and earlier classified, orphans indeed are fast-evolving sequences. Finally, >90% of the detected ODs are located at the protein termini, which suggests that these orphans could have been created by mutations that have affected the start or stop codons.

Evaluating dosage compensation as a cause of duplicate gene retention in Paramecium tetraurelia.

The high retention of duplicate genes in the genome of Paramecium tetraurelia has led to the hypothesis that most of the retained genes have persisted because of constraints due to gene dosage. This and other possible mechanisms are discussed in the light of expectations from population genetics and systems biology.

Electronic screening and brief intervention for risky drinking in Swedish university students — A randomized controlled trial

BACKGROUND The limited number of electronic screening and brief intervention (e-SBI) projects taking place in young adult student populations has left knowledge gaps about the specific methods needed to motivate reduced drinking. The aim of the present study was to compare differences in alcohol consumption over time after a series of e-SBIs was conducted with two groups of young adult students who were considered risky drinkers. The intervention group (IG) (n=80) received extensive normative feedback; the control group (CG) (n=78) received very brief feedback consisting of only three statements. METHOD An e-SBI project was conducted in naturalistic settings among young adult students at a Swedish university. This study used a randomized controlled trial design, with respondents having an equal chance of being assigned to either the IG or the CG. The study assessed changes comparing the IG with the CG on four alcohol-related measurements: proportion with risky alcohol consumption, average weekly alcohol consumption, frequency of heavy episodic drinking (HED) and peak blood alcohol concentration (BAC). Follow-up was performed at 3 and 6 months after baseline. RESULTS The study documented a significant decrease in the average weekly consumption for the IG over time but not for the CG, although the differences between the groups were non-significant. The study also found that there were significant decreases in HED over time within both groups; the differences were about equal in both groups at the 6-month follow-up. The proportion of risky drinkers decreased by about a third in both the CG and IG at the 3- and 6-month follow-ups. CONCLUSIONS As the differences between the groups at 6 months for all alcohol-related outcome variables were not significant, the shorter, generic brief intervention appears to be as effective as the longer one including normative feedback. However, further studies in similar naturalistic settings are warranted with delayed assessment groups as controls in order to increase our understanding of reactivity assessment in email-based interventions among students.

Unintentional drowning in northern Iran : A population-based study

The Iranian Ministry of Health documented that about 1500 people died from drowning annually in Iran between years 2000 and 2001. This study is a descriptive, retrospective, population-based analysis of 342 unintentional drowning deaths occurring to residents and tourists in Guilan and Mazandran Provinces in Iran over a 1-year period (2005-2006), using multiple data sources. The findings from this study demonstrate that the drowning rate for residents of the study population, 4.24 per 100,000, is much higher than drowning rates for populations in developed economies in Europe. Risk factors for drowning in the study populations include male gender, young age, and swimming in unsupervised areas. Drownings occurred most frequently in rivers, followed by canals and lakes. While much more remains to be done to investigate the problems associated with drowning deaths and injuries in Iran, the information obtained from this study can help point the way to targeted interventions.

Epitope-specific antibody response is controlled by immunoglobulin VH polymorphisms

Epitope-specific antibody responses recognized by germline-encoded structures are of significant relevance for the development of autoantibody-mediated autoimmune diseases.

Long indels are disordered: A study of disorder and indels in homologous eukaryotic proteins☆

Proteins evolve through point mutations as well as by insertions and deletions (indels). During the last decade it has become apparent that protein regions that do not fold into three-dimensional structures, i.e. intrinsically disordered regions, are quite common. Here, we have studied the relationship between protein disorder and indels using HMM-HMM pairwise alignments in two sets of orthologous eukaryotic protein pairs. First, we show that disordered residues are much more frequent among indel residues than among aligned residues and, also are more prevalent among indels than in coils. Second, we observed that disordered residues are particularly common in longer indels. Disordered indels of short-to-medium size are prevalent in the non-terminal regions of proteins while the longest indels, ordered and disordered alike, occur toward the termini of the proteins where new structural units are comparatively well tolerated. Finally, while disordered regions often evolve faster than ordered regions and disorder is common in indels, there are some previously recognized protein families where the disordered region is more conserved than the ordered region. We find that these rare proteins are often involved in information processes, such as RNA processing and translation. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly.