We traced the genesis and regulatory wiring of the Metaviridaederived domesticated genes (DGs) through phylogenomic analysis, using wholegenome information from more than 90 chordate genomes. Mammalian retroelementderived DGs (RDDGs) have been shown to originate in several steps by independent domestication events and to diversify later by gene duplications. Analysis of syntenic loci has shown that diverse RDDGs and their chromosomal positions were fully established in the ancestor of placental mammals. By analysis of active Metaviridae lineages in amniotes, we have demonstrated that RDDGs originated from retroelement remains. During the domestication process, de novo acquisition of regulatory regions is shown to be a prerequisite for the survival of the DGs. The origin and evolution of de novo acquired promoters and untranslated regions in diverse mammalian RDDGs have been explained by comparative analysis of orthologous gene loci. The origin of placental mammalspecific innovations and adaptations, such as placenta and newly evolved brain functions, was most probably connected to the regulatory wiring of DGs and their rapid fixation in the ancestor of placental mammals.
COBISS.SI-ID: 26492711
AID/APOBEC proteins are cytidine deaminases, which act within the innate immune response to protect the genome against the harmful effects of retroelements. The protective activity of mammalian APOBEC proteins is evident from clusters of hypermutations present in retroelements of mammalian genomes, but their role in host defense and their impact on genome evolution in other vertebrates is not known. In this study, we report the first evidence of cytidine deaminase activity in nonmammalian vertebrates, in the green anole lizard genome, where the oldest known APOBEC1 (A1) protein was recently discovered. Our results confirm that the lizard A1 protein is a potent cytidine deaminase and an inhibitor of retrotransposition. Our comparative analysis of the antiretroelement activity of lizard and human APOBEC proteins showed that the mechanism of A1induced LINE inhibition is evolutionary conserved and significantly different from that of human A3 proteins. Together with the editing detected in vertebrate LINE elements, our study indicates that AID/APOBEC antiretroelement activity originates in early vertebrates. Our findings open new perspectives in AID/APOBEC protein research and are an important contribution to our understanding of their physiological roles and their impact on the evolution of vertebrate genomes.
COBISS.SI-ID: 27367975
We were able to show for the first time that human group X secreted phospholipase A2 (hGX sPLA2) induces lipid droplet (LD) formation in the highly tumorigenic MDAMB231 breast cancer cells in an enzyme activitydependent manner, thereby stimulating cell proliferation and significantly prolonging cell survival under serum deprivationinduced stress. Our results suggested that free fatty acids, in particular oleic acid, released from membrane phospholipids by the action of hGX sPLA2, are substantially responsible for LD biogenesis and cell survival. It was also demonstrated that the mechanism of hGXinduced cell survival and lipid accumulation is associated with alterations in the expression of key lipogenic and βoxidation enzymes, and modulation of AMPactivated protein kinase (AMPK) and protein B/Akt kinase signalling pathways. The protumorigenic effects induced by hGX sPLA2 were abolished by etomoxir, suggesting a critical role for βoxidation in hGXinduced LD formation and cell survival in breast cancer cells. The ability of hGX sPLA2 to act as a modulator of basic lipid metabolism and cancer cell survival is thus well established. This could have important implications in elucidating the role of hGX and other sPLA2s, such as hGV and hGIII, in cancer and human pathophysiology in general.
COBISS.SI-ID: 27087655
For some decades, cone snail venoms have been providing peptides, generally termed conopeptides, that exhibit a large diversity of pharmacological properties. However, little attention has been devoted to the high molecular mass (HMM) proteins in venoms of mollusks. In order to shed more light on cone snail venom HMM components, the proteins of dissected and injected venom of a fishhunting cone snail, Conus consors, were extensively assessed. HMM venom proteins were separated by twodimensional polyacrylamide gel electrophoresis and analyzed by mass spectrometry (MS). The MS data were interpreted using UniProt database, EST libraries from C. consors venom duct and salivary gland, and their genomic information. Numerous protein families were discovered in the lumen of the venom duct and assigned a biological function, thus pointing to their potential role in venom production and maturation. Interestingly, the study also revealed original proteins defining new families of unknown function. Only two groups of HMM proteins passing the venom selection process – echotoxins and hyaluronidases – were clearly present in the injected venom. They are suggested to contribute to the envenomation process. This newly devised integrated HMM proteomic analysis is a big step towards identification of the protein arsenal used in a cone snail venom apparatus for venom production, maturation and function. This work represents the first integral proteomic study performed exclusively by Slovenian researchers, on equipment instaled in Slovenia. By the Slovenian Research Agency, this work was proclaimed as exceptional scientific achievement in 2012 in the field of NaturalMathematical Sciences in RS.
COBISS.SI-ID: 26042407
We showed that the poreforming protein perforin (PFN) is able to induce invaginations and formation of complete internal vesicles in giant and large unilamellar vesicles. Membrane capacitance measurements showed that PFN is able to increase a planar lipid membrane surface area in the absence of pore formation. Addition of PFN to Jurkat cells caused the formation of internal vesicles prior to pores and triggered an endocytosislike event in addition to pore formation. By the Slovenian Research Agency, this work was proclaimed as exceptional scientific achievement in 2011 in the field of NaturalMathematical Sciences in RS.
COBISS.SI-ID: 2493519