The Dispanins: A Novel Gene Family of Ancient Origin That Contains 14 Human Members

The Interferon induced transmembrane proteins (IFITM) are a family of transmembrane proteins that is known to inhibit cell invasion of viruses such as HIV-1 and influenza. We show that the IFITM genes are a subfamily in a larger family of transmembrane (TM) proteins that we call Dispanins, which refers to a common 2TM structure. We mined the Dispanins in 36 eukaryotic species, covering all major eukaryotic groups, and investigated their evolutionary history using Bayesian and maximum likelihood approaches to infer a phylogenetic tree. We identified ten human genes that together with the known IFITM genes form the Dispanin family. We show that the Dispanins first emerged in eukaryotes in a common ancestor of choanoflagellates and metazoa, and that the family later expanded in vertebrates where it forms four subfamilies (A–D). Interestingly, we also find that the family is found in several different phyla of bacteria and propose that it was horizontally transferred to eukaryotes from bacteria in the common ancestor of choanoflagellates and metazoa. The bacterial and eukaryotic sequences have a considerably conserved protein structure. In conclusion, we introduce a novel family, the Dispanins, together with a nomenclature based on the evolutionary origin

DNA methylation correlation networks in overweight and normal-weight adolescents reveal differential coordination

Multiple health issues are associated with obesity and numerous factors are causative of the disease. The role of genetic factors is well established, as is the knowledge that dietary and sedentary behavior promotes weight gain. Although there is strong suspicion towards the role of epigenetics as a driving force toward disease, this field remains l in the context of obesity. DNA methylation correlation networks were profiled from blood samples of 69 adolescents of two distinct weight-classes; obese (n=35) and normal-weight (n=34). The network analysis revealed major differences in the organization of the networks where the network of the obese had less modularity compared to normal-weight. This is manifested by more and smaller clusters in the obese, pertaining to genes of related functions and pathways, than the network of the normal-weight. Consequently, this suggests that biological pathways have a lower order of coordination between each other in means of DNA methylation in obese than normal-weight. Analysis of highly connected genes, hubs, in the two networks suggests that the difference in coordination between biological pathways may be derived by changes of the methylation pattern of these hubs; highly connected genes in one network had an intriguingly low connectivity in the other. In conclusion, the results suggest differential regulation of transcription through changes in the coordination of DNA methylation in overweight and normal weighted individuals. The findings of this study are a major step towards understanding the role of DNA methylation in obesity and provide potential biomarkers for diagnosing and predicting obesity

Multiple sequence alignment of the <i>Dispanins</i>.

<p>The multiple sequence alignment shows the conserved regions around the two transmembrane helices in the <i>Dispanins</i>. Consensus protein sequences of each vertebrate subfamily together with invertebrates, <i>M. brevicollis</i> (Mb) and a bacterial consensus sequences are included Conserved residues are coloured according to the Zappo scheme in Jalview and well conserved motifs are marked with a square. The conserved splice site between the two transmembrane helices is marked with a red line.</p

The protein features and topology of the <i>Dispanin</i> subfamilies.

<p>The picture shows the membrane topology and sequences features of a representative human member of each subfamily. Conserved motifs and residues are shown and those which have a sequence identity of more than 90% are framed in black and those with 80–90% sequence similarity are framed in blue. Predicted phosphorylation (Green) and glycosylation (orange) sites are shown.</p