Genetic structure and evolution of the Vps25 family, a yeast ESCRT-II component

BACKGROUND: Vps25p is the product of yeast gene VPS25 and is found in an endosomal sorting complex required for transport (ESCRT)-II, along with Vps22p and Vps36p. This complex is essential for sorting of ubiquitinated biosynthetic and endosomal cargoes into endosomes. RESULTS: We found that VPS25 is a highly conserved and widely expressed eukaryotic gene, with single orthologs in chromalveolate, excavate, amoebozoan, plant, fungal and metazoan species. Two paralogs were found in Trichomonas vaginalis. An ortholog was strikingly absent from the Encephalitozoon cuniculi genome. Intron positions were analyzed in VPS25 from 36 species. We found evidence for five ancestral VPS25 introns, intron loss, and single instances of intron gain (a Paramecium species) and intron slippage (Theileria species). Processed pseudogenes were identified in four mammalian genomes, with a notable absence in the mouse genome. Two retropseudogenes were found in the chimpanzee genome, one more recently inserted, and one evolving from a common primate ancestor. The amino acid sequences of 119 Vps25 orthologs are aligned, compared with the known secondary structure of yeast Vps25p, and used to carry out phylogenetic analysis. Residues in two amino-terminal PPXY motifs (motif I and II), involved in dimerization of Vps25p and interaction with Vps22p and Vps36p, were closely, but not absolutely conserved. Specifically, motif I was absent in Vps25 homologs of chromalveolates, euglenozoa, and diplomonads. A highly conserved carboxy-terminal lysine was identified, which suggests Vps25 is ubiquitinated. Arginine-83 of yeast Vps25p involved in Vps22p interaction was highly, but not absolutely, conserved. Human tissue expression analysis showed universal expression. CONCLUSION: We have identified 119 orthologs of yeast Vps25p. Expression of mammalian VPS25 in a wide range of tissues, and the presence in a broad range of eukaryotic species, indicates a basic role in eukaryotic cell function. Intron splice site positions were highly conserved across all major eukaryotic species, suggesting an ancestral origin. Amino acid sequence analysis showed the consensus for the amino-terminal proline-rich motifs is P- [WP]-X-[YF] for motif I (when present) and P-P-[FYL]-[FY] for motif II, and that Vps25 may be ubiquitinated

Connecting Cline Library with tribal communities: A case study

Northern Arizona University (NAU) is a public state university with a commitment to Native American students (Hughes and Tsosie 2013). The university’s Cline Library strongly supports the values of academic excellence, student engagement, and student success. NAU is a unique academic institution because it has a Native student community population of 4%; according to the National Center for Educational Statistics, in 2006 Native students at US universities averaged only 1% of the entire student population. As of 2016, the Native American population at NAU was 825 students. Compared to the overall student population Native students comprise about 3% of student growth. In 2005 NAU’s strategic plan defined a commitment to Native Americans and to “become one of the nation’s leading universities serving Native Americans.” This goal is currently under revision by the university’s Commission for Native Americans and the Vice President for Native American Affairs (Chad Hamill, PhD). What does this goal mean for the university? This is the only goal in the university’s strategic plan where a specific community is mentioned and highlighted as a priority. The institution’s commitment to serving Native Americans has a direct impact on the recruitment, retention, and graduation rates for Native American students. The university commitment to developing collaborative services and outreach programs to Native American communities and promoting engagement and appreciation of Native American cultures and tribal nations within the university and broader community is still a top goal (NAU Strategic Plan 2005-2010). Today over a hundred tribes from across the country are represented at NAU. A large portion of students come from the geographic region of Northern Arizona and New Mexico. Beginning in 2008, Cline Library sought out ways in which it could align its activities with the university's strategic commitment to serving Native Americans. Cline librarians and archivists work to support indigenous students, researchers, scholars, and communities through collecting and preserving Indigenous scholarship. In order to achieve the university’s commitment to Native Americans Cline Library needs a robust collection and services available for Native students. This paper will focus on themes that emerge from a critical analysis of the library’s collections and their work with American Indian communities. It will start by describing how the library applies concepts of critical librarianship and teaching and learning to collection development. The conversation continues with the critical role of librarians and archivists at Cline Library in supporting faculty and students. Finally, as an independent yet integrated department, the library’s Special Collections and Archives unit responds to the Native American community’s tribal concerns with the collaborative management of cultural materials in ways that balance archival theory and practice with access to sensitive information. The conclusion offers strategies to improve on existing efforts at Cline and ties together many of the themes woven throughout the article

Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein–ubiquitin conjugates

There is increasing evidence that ubiquitination of receptors provides an important endosomal sorting signal. Here we report that mammalian class E vacuolar protein-sorting (vps) proteins recognize ubiquitin. Both tumor susceptibility gene 101 (TSG101)/human VPS (hVPS)28 and hepatocyte growth factor receptor substrate (Hrs) cytosolic complexes bind ubiquitin-agarose. TSG101 and hVPS28 are localized to endosomes that contain internalized EGF receptor and label strongly for ubiquitinated proteins. Microinjection of anti-hVPS28 specifically retards EGF degradation and leads to endosomal accumulation of ubiquitin–protein conjugates. Likewise, depletion of TSG101 impairs EGF trafficking and causes dramatic relocalization of ubiquitin to endocytic compartments. Similar defects are found in cells overexpressing Hrs, further emphasizing the links between class E protein function, receptor trafficking, and endosomal ubiquitination

Characterization of the Deleted in Autism 1 Protein Family: Implications for Studying Cognitive Disorders

Autism spectrum disorders (ASDs) are a group of commonly occurring, highly-heritable developmental disabilities. Human genes c3orf58 or Deleted In Autism-1 (DIA1) and cXorf36 or Deleted in Autism-1 Related (DIA1R) are implicated in ASD and mental retardation. Both gene products encode signal peptides for targeting to the secretory pathway. As evolutionary medicine has emerged as a key tool for understanding increasing numbers of human diseases, we have used an evolutionary approach to study DIA1 and DIA1R. We found DIA1 conserved from cnidarians to humans, indicating DIA1 evolution coincided with the development of the first primitive synapses. Nematodes lack a DIA1 homologue, indicating Caenorhabditis elegans is not suitable for studying all aspects of ASD etiology, while zebrafish encode two DIA1 paralogues. By contrast to DIA1, DIA1R was found exclusively in vertebrates, with an origin coinciding with the whole-genome duplication events occurring early in the vertebrate lineage, and the evolution of the more complex vertebrate nervous system. Strikingly, DIA1R was present in schooling fish but absent in fish that have adopted a more solitary lifestyle. An additional DIA1-related gene we named DIA1-Like (DIA1L), lacks a signal peptide and is restricted to the genomes of the echinoderm Strongylocentrotus purpuratus and cephalochordate Branchiostoma floridae. Evidence for remarkable DIA1L gene expansion was found in B. floridae. Amino acid alignments of DIA1 family gene products revealed a potential Golgi-retention motif and a number of conserved motifs with unknown function. Furthermore, a glycine and three cysteine residues were absolutely conserved in all DIA1-family proteins, indicating a critical role in protein structure and/or function. We have therefore identified a new metazoan protein family, the DIA1-family, and understanding the biological roles of DIA1-family members will have implications for our understanding of autism and mental retardation

Reactive stress-coping styles show more variable reproductive expenditure and fitness outcomes

Stress-coping styles dictate how individuals react to stimuli and can be measured by the integrative physiological parameter of resting heart-rate variability (HRV); low resting HRV indicating proactive coping styles, while high resting HRV typifies reactive individuals. Over 5 successive breeding seasons we measured resting HRV of 57 lactating grey seals. Mothers showed consistent individual differences in resting HRV across years. We asked whether proactive and reactive mothers differed in their patterns of maternal expenditure and short-term fitness outcomes within seasons, using maternal daily mass loss rate to indicate expenditure, and pup daily mass gain to indicate within season fitness outcomes. We found no difference in average rates of maternal daily mass loss or pup daily mass gain between proactive and reactive mothers. However, reactive mothers deviated more from the sample mean for maternal daily mass and pup daily mass gain than proactive mothers. Thus, while proactive mothers exhibit average expenditure strategies with average outcomes, expenditure varies much more among reactive mothers with more variable outcomes. Overall, however, mean fitness was equal across coping styles, providing a mechanism for maintaining coping style diversity within populations. Variability in reactive mothers’ expenditures and success is likely a product of their attempts to match phenotype to prevailing environmental conditions, achieved with varying degrees of success