Snake mitochondrial genomes: phylogenetic relationships and implications of extended taxon sampling for interpretations of mitogenomic evolution

<p>Abstract</p> <p>Background</p> <p>Snake mitochondrial genomes are of great interest in understanding mitogenomic evolution because of gene duplications and rearrangements and the fast evolutionary rate of their genes compared to other vertebrates. Mitochondrial gene sequences have also played an important role in attempts to resolve the contentious phylogenetic relationships of especially the early divergences among alethinophidian snakes. Two recent innovative studies found dramatic gene- and branch-specific relative acceleration in snake protein-coding gene evolution, particularly along internal branches leading to Serpentes and Alethinophidia. It has been hypothesized that some of these rate shifts are temporally (and possibly causally) associated with control region duplication and/or major changes in ecology and anatomy.</p> <p>Results</p> <p>The near-complete mitochondrial (mt) genomes of three henophidian snakes were sequenced: <it>Anilius scytale</it>, <it>Rhinophis philippinus</it>, and <it>Charina trivirgata</it>. All three genomes share a duplicated control region and translocated tRNA^LEU, derived features found in all alethinophidian snakes studied to date. The new sequence data were aligned with mt genome data for 21 other species of snakes and used in phylogenetic analyses. Phylogenetic results agreed with many other studies in recovering several robust clades, including Colubroidea, Caenophidia, and Cylindrophiidae+Uropeltidae. Nodes within Henophidia that have been difficult to resolve robustly in previous analyses remained uncompellingly resolved here. Comparisons of relative rates of evolution of rRNA vs. protein-coding genes were conducted by estimating branch lengths across the tree. Our expanded sampling revealed dramatic acceleration along the branch leading to Typhlopidae, particularly long rRNA terminal branches within Scolecophidia, and that most of the dramatic acceleration in protein-coding gene rate along Serpentes and Alethinophidia branches occurred before <it>Anilius </it>diverged from other alethinophidians.</p> <p>Conclusions</p> <p>Mitochondrial gene sequence data alone may not be able to robustly resolve basal divergences among alethinophidian snakes. Taxon sampling plays an important role in identifying mitogenomic evolutionary events within snakes, and in testing hypotheses explaining their origin. Dramatic rate shifts in mitogenomic evolution occur within Scolecophidia as well as Alethinophidia, thus falsifying the hypothesis that these shifts in snakes are associated exclusively with evolution of a non-burrowing lifestyle, macrostomatan feeding ecology and/or duplication of the control region, both restricted to alethinophidians among living snakes.</p

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenLoss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.US National Institutes of Health (NIH) Training 5-T32-GM007748-33 Doris Duke Charitable Foundation 2006087 Fulbright Diabetes UK Fellowship BDA 11/0004348 Broad Institute from Pfizer, Inc. NIH U01 DK085501 U01 DK085524 U01 DK085545 U01 DK085584 Swedish Research Council Dnr 521-2010-3490 Dnr 349-2006-237 European Research Council (ERC) GENETARGET T2D GA269045 ENGAGE 2007-201413 CEED3 2008-223211 Sigrid Juselius Foundation Folkh lsan Research Foundation ERC AdG 293574 Research Council of Norway 197064/V50 KG Jebsen Foundation University of Bergen Western Norway Health Authority Lundbeck Foundation Novo Nordisk Foundation Wellcome Trust WT098017 WT064890 WT090532 WT090367 WT098381 Uppsala University Swedish Research Council and the Swedish Heart- Lung Foundation Academy of Finland 124243 102318 123885 139635 Finnish Heart Foundation Finnish Diabetes Foundation, Tekes 1510/31/06 Commission of the European Community HEALTH-F2-2007-201681 Ministry of Education and Culture of Finland European Commission Framework Programme 6 Integrated Project LSHM-CT-2004-005272 City of Kuopio and Social Insurance Institution of Finland Finnish Foundation for Cardiovascular Disease NIH/NIDDK U01-DK085545 National Heart, Lung, and Blood Institute (NHLBI) National Institute on Minority Health and Health Disparities N01 HC-95170 N01 HC-95171 N01 HC-95172 European Union Seventh Framework Programme, DIAPREPP Swedish Child Diabetes Foundation (Barndiabetesfonden) 5U01DK085526 DK088389 U54HG003067 R01DK072193 R01DK062370 Z01HG000024info:eu-repo/grantAgreement/EC/FP7/20201

bothcountries_species_richness_longformat

Number of individuals for each bird species on all trees observed including zeros. country: country tree was observed in (Nicaragua or Colombia); year: year of observation (2016); treesp: common name of tree species observed (see paper for species names); bird_sp: common name (Colombia) or code (Nicaragua) for each bird species observed; count: number of individuals observed (including zeros if never observed foraging in a tree species)

Peak fit analysis of mosasaur and monitor lizard IR spectra.

<p>(A) Peak fit analysis of the blue <i>Prognathodon</i> spectrum presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019445#pone-0019445-g005" target="_blank">Figures 5B, C</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019445#pone-0019445-g006" target="_blank">6A</a>. (B) Peak fit analysis of the <i>Varanus</i> spectrum shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019445#pone-0019445-g005" target="_blank">Figures 5C</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0019445#pone-0019445-g006" target="_blank">6A</a>. The background of both spectra was subtracted using the Opus Concave rubber band correction method found in the Bruker OPUS 6.5 software package. Default values were used; i.e., 10 iterations and 64 baseline points. This correction marginally influenced peak fitting, positions and intensities, compared to those of a simple straight line subtraction, indicating a well-behaved and stable background. (C) Correlation diagram for frequencies obtained in the peak fit analyses of the <i>Prognathodon</i> and <i>Varanus</i> spectra.</p

Partially mineralized fiber bundle obtained from IRSNB 1624.

<p>(A) Scanning electron micrograph of a partly mineralized fiber bundle located in between mineralized fragments of vessel-like structures. (B) Close up of the area marked in A showing partly mineralized fibers (arrows – note transition from mineralized to organic part of the fibers) and osteocyte-like entities (arrowheads).</p