AbstractsBiology & Animal Science

The right-hand-shaped polymerases comprising the DNA/RNA polymerase superfamily represent at least six different protein families containing replicases, transcriptases and repair proteins from all three domains of life as well as from their viruses. All of these polymerases have at least three subdomains: fingers, palm and thumb, which form together a structure resembling a right-hand. The catalytic site is located in the palm subdomain, in which polymerization process is catalysed by two Mg2+ ions. There can also be additional ions such as the non-catalytic ion in the RNA-dependent RNA polymerase of phage φ6, which is located approximately 6 Ångströms from the catalytic site. The phylogeny and common regions of the right-hand-shaped polymerases have been previously studied mainly using amino acid sequence alignments. However, the sequence similarity between polymerases belonging into different protein families is low and therefore, the structure alignment provides a potential alternative because protein structures can retain similarity longer in evolution than amino acid sequences. In this thesis, the common structural features between and within the families of the right-hand-shaped polymerases are described, and based on the structural cores the phylogenetic trees are deduced. In addition, the phylogenetic relationships between the right-hand-shaped polymerases and other structurally related proteins are described. As results, it is shown that a phylogenetic tree following the established boundaries of protein families is possible to construct based on structural core sharing no sequence identity. This tree, illustrating long distance phylogenetic relationships suggests that the known right-hand-shaped polymerase families are not the closest relatives to each other. The phylogenies within polymerase families suggest that the relationships among the polymerases do not always follow the evolution of the corresponding organism, which implies horizontal gene transfer between cells, and cells and viruses. The phylogeny of RNA virus RNA polymerases seem to be dependent on the priming mechanism and it does not follow the virion architecture or the Baltimore classification. In addition, the viral RNA-dependent RNA polymerases seem to share a third ion binding site in the proximity of catalytic site. Polymeraasit ovat elämälle välttämättömiä proteiinimolekyylejä. Niillä on välttämätön rooli genomin kopioinnissa, geenien ilmentämisessä sekä mutaatioiden korjaamisessa. Oikeakätiset polymeraasit muistuttavat rakenteeltaan oikeaa kättä ja niiden rakenne jaetaan kolmeen osaan: kämmeneen, sormiin ja peukaloon. Tällaisia polymeraaseja tunnetaan kaikista kolmesta elämän domeenista: eukaryooteista, bakteereista ja arkeoneista. Tämän lisäksi monilla viruksilla on vähintään yksi oikeakätinen polymeraasi. Nukleotidin, eli DNA:n tai RNA:n rakenneyksikön, lisääminen osaksi ketjua tapahtuu kämmenessä, jossa kaksi magnesium-ionia katalysoi reaktiota. Lisäksi, RNA virusten RNA polymeraaseilla on havaittu katalyyttisten ionien…