Structural and Functional Evolution of the Trace Amine-Associated Receptors TAAR3, TAAR4 and TAAR5 in Primates

The family of trace amine-associated receptors (TAAR) comprises 9 mammalian TAAR subtypes, with intact gene and pseudogene numbers differing considerably even between closely related species. To date the best characterized subtype is TAAR1, which activates the Gs protein/adenylyl cyclase pathway upon stimulation by trace amines and psychoactive substances like MDMA or LSD. Recently, chemosensory function involving recognition of volatile amines was proposed for murine TAAR3, TAAR4 and TAAR5. Humans can smell volatile amines despite carrying open reading frame (ORF) disruptions in TAAR3 and TAAR4. Therefore, we set out to study the functional and structural evolution of these genes with a special focus on primates. Functional analyses showed that ligands activating the murine TAAR3, TAAR4 and TAAR5 do not activate intact primate and mammalian orthologs, although they evolve under purifying selection and hence must be functional. We also find little evidence for positive selection that could explain the functional differences between mouse and other mammals. Our findings rather suggest that the previously identified volatile amine TAAR3–5 agonists reflect the high agonist promiscuity of TAAR, and that the ligands driving purifying selection of these TAAR in mouse and other mammals still await discovery. More generally, our study points out how analyses in an evolutionary context can help to interpret functional data generated in single species

Involvement of the V2 Vasopressin Receptor in Adaptation to Limited Water Supply

Mammals adapted to a great variety of habitats with different accessibility to water. In addition to changes in kidney morphology, e.g. the length of the loops of Henle, several hormone systems are involved in adaptation to limited water supply, among them the renal-neurohypophysial vasopressin/vasopressin receptor system. Comparison of over 80 mammalian V2 vasopressin receptor (V2R) orthologs revealed high structural and functional conservation of this key component involved in renal water reabsorption. Although many mammalian species have unlimited access to water there is no evidence for complete loss of V2R function indicating an essential role of V2R activity for survival even of those species. In contrast, several marsupial V2R orthologs show a significant increase in basal receptor activity. An increased vasopressin-independent V2R activity can be interpreted as a shift in the set point of the renal-neurohypophysial hormone circuit to realize sufficient water reabsorption already at low hormone levels. As found in other desert mammals arid-adapted marsupials show high urine osmolalities. The gain of basal V2R function in several marsupials may contribute to the increased urine concentration abilities and, therefore, provide an advantage to maintain water and electrolyte homeostasis under limited water supply conditions

Investigating the seafloor below the Ekström Ice Shelf: the Sub-EIS-Obs project at East Antarctica’s continental margin

Knowledge of sub-ice shelf sedimentary sequences, ice-ocean interactions, and biological activities is still relatively sparse, largely due to the challenges involved in accessing ice shelf cavities. The Sub-EIS-Obs project, funded by the Alfred-Wegener-Institute (AWI) and the Federal Institute for Geosciences and Natural Resources (BGR) in Germany, is a multidisciplinary study, which aims to recover and characterize sediment sequences beneath the Ekström Ice Shelf (EIS) in East Antarctica. The project addresses several research objectives, such as the crustal evolution during the breakup of Gondwana, the build-up and variability of the East Antarctic Ice Sheet (EAIS) throughout the Cenozoic, reconstruction of grounding-line dynamics, sedimentary and erosional processes beneath the ice stream and shelf, and multidisciplinary observations of climate induced changes in ice-ocean interactions. A pre-site seismic survey campaign was carried out on the Ekström Ice Shelf in 2016/2017 and 2017/2018, resulting in 615 km of multi-fold seismic data. Based on these data, four different units were defined, which, according to preliminary interpretation, document geologic history of the breakup of Gondwana in the Jurassic (Explora-Wedge volcanic deposits) and ongoing marine and glacio-marine sedimentation during the Meso- and Cenozoic. On top of all strata a glacio-marine surface cover deposited during the Last Glacial Maximum and Holocene sedimentation is indicated in the seismic profiles. In order to sample all units separately, coring locations were selected accordingly. A hot water drilling system was used to drill holes through the shelf ice (ice thicknessesrange between∼210 and 330 m), enabling the deployment of a gravity corer, a Wippermann Grabber, a vibro-and a hammer coring system manufactured by Jilin University (Changchun, China), and a UWITEC percussioncorer (BAS corer). Moreover, a camera installed in a pressure housing enabled recording of high-resolution videofootage of the seafloor and associated benthic ecosystems as well as the base of the ice shelf. In addition, a Conductivity-Temperature-Depth probe was attached to all coring devices in order to record the oceanographic properties of the water column. Here, we present first results from the Sub-EIS-Obs sediment sampling campaigns 2017/2018 and 2018/2019. We present an overview of the long-term project aims, sampling strategy, perfor-mance of the hot water drilling operation, and recovered geological samples, and the video footages of the seafloor

Genetic Diversity among Ancient Nordic Populations

Using established criteria for work with fossil DNA we have analysed mitochondrial DNA from 92 individuals from 18 locations in Denmark ranging in time from the Mesolithic to the Medieval Age. Unequivocal assignment of mtDNA haplotypes was possible for 56 of the ancient individuals; however, the success rate varied substantially between sites; the highest rates were obtained with untouched, freshly excavated material, whereas heavy handling, archeological preservation and storage for many years influenced the ability to obtain authentic endogenic DNA. While the nucleotide diversity at two locations was similar to that among extant Danes, the diversity at four sites was considerably higher. This supports previous observations for ancient Britons. The overall occurrence of haplogroups did not deviate from extant Scandinavians, however, haplogroup I was significantly more frequent among the ancient Danes (average 13%) than among extant Danes and Scandinavians (∼2.5%) as well as among other ancient population samples reported. Haplogroup I could therefore have been an ancient Southern Scandinavian type “diluted” by later immigration events. Interestingly, the two Neolithic samples (4,200 YBP, Bell Beaker culture) that were typed were haplogroup U4 and U5a, respectively, and the single Bronze Age sample (3,300–3,500 YBP) was haplogroup U4. These two haplogroups have been associated with the Mesolithic populations of Central and Northern Europe. Therefore, at least for Southern Scandinavia, our findings do not support a possible replacement of a haplogroup U dominated hunter-gatherer population by a more haplogroup diverse Neolithic Culture

Structural and functional evolution of the P2Y12-like receptor group

Metabotropic pyrimidine and purine nucleotide receptors (P2Y receptors) belong to the superfamily of G protein-coupled receptors (GPCR). They are distinguishable from adenosine receptors (P1) as they bind adenine and/or uracil nucleotide triphosphates or diphosphates depending on the subtype. Over the past decade, P2Y receptors have been cloned from a variety of tissues and species, and as many as eight functional subtypes have been characterized. Most recently, several members of the P2Y12-like receptor group, which includes the clopidogrel-sensitive ADP receptor P2Y12, have been deorphanized. The P2Y12-like receptor group comprises several structurally related GPCR which, however, display heterogeneous agonist specificity including nucleotides, their derivatives, and lipids. Besides the established function of P2Y12 in platelet activation, expression in macrophages, neuronal and glial cells as well as recent results from functional studies implicate that several members of this group may have specific functions in neurotransmission, inflammation, chemotaxis, and response to tissue injury. This review focuses specifically on the structure-function relation and shortly summarizes some aspects of the physiological relevance of P2Y12-like receptor members

Cox26 is a novel stoichiometric subunit of the yeast cytochrome c oxidase.

The cytochrome c oxidase (COX) is the terminal enzyme of the respiratory chain. The complex accepts electrons from cytochrome c and passes them onto molecular oxygen. This process contributes to energy capture in the form of a membrane potential across the inner membrane. The enzyme complex assembles in a stepwise process from the three mitochondria-encoded core subunits Coxl, Cox2 and Cox3, which associate with nuclear-encoded subunits and cofactors. In the yeast Saccharomyces cerevisiae, the cytochrome c oxidase associates with the bc(1)-complex into supercomplexes, allowing efficient energy transduction. Here we report on Cox26 as a protein found in respiratory chain supercomplexes containing cytochrome c oxidase. Our analyses reveal Cox26 as a novel stoichiometric structural subunit of the cytochrome c oxidase. A loss of Cox26 affects cytochrome c oxidase activity and respirasome organization

Search for a platelet-activating factor receptor in the Trypanosoma cruzi proteome: a potential target for Chagas disease chemotherapy

Chagas disease (CD) causes the highest burden of parasitic diseases in the Western Hemisphere and is therefore a priority for drug research and development. Platelet-activating factor (PAF) causes the CD parasite Trypanosoma cruzi to differentiate, which suggests that the parasite may express PAF receptors. Here, we explored the T. cruzi proteome for PAF receptor-like proteins. From a total of 23,000 protein sequences, we identified 29 hypothetical proteins that are predicted to have seven transmembrane domains (TMDs), which is the main characteristic of the G protein-coupled receptors (GPCRs), including the PAF receptor. The TMDs of these sequences were independently aligned with domains from 25 animal PAF receptors and the sequences were analysed for conserved residues. The conservation score mean values for the TMDs of the hypothetical proteins ranged from 31.7-44.1%, which suggests that if the putative T. cruzi PAF receptor is among the sequences identified, the TMDs are not highly conserved. These results suggest that T. cruzi contains several GPCR-like proteins and that one of these GPCRs may be a PAF receptor. Future studies may further validate the PAF receptor as a target for CD chemotherapy