On the origin of papillomavirus proteins
Date
2019-07-08
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Abstract
Viirused on parasiitse eluviisiga bioloogilised objektid, mis kasutavad peremeesraku ressursse endi paljundamiseks. Erinevalt rakulistest organismidest puudub viirustel ühine eellane. Nende tekke kohta eksisteerib mitmeid hüpoteese, kuid viiruste täpne päritolu on tänini ebaselge.
Antud doktoritöös keskenduti papilloomiviiruse (PV) sugukonna päritolu uuringutele. PV-d on võimelised nakatama imetajaid, linde, roomajaid ja ka kalu. Kõrge riskiga inimese PV-d põhjustavad enamiku emakakaelavähi juhtudest ja on ka paljude teiste kasvajate tekitajad. Uuringu käigus analüüsiti erinevaid järjestuste andmebaase, tuvastamaks PV-des leiduvate valgugeenide homolooge (ühtset päritolu geene) rakulistes organismides. Tulemused näitasid, et rakuliste organismide genoomides leidub vaid PV-te replikatsioonivalgu E1 homolooge, jättes PV-te päritolu siiski veel ebaselgeks. Samas näitasid meie tulemused, et PV-d on evolutsiooniliselt suguluses polüoomiviiruste ja parvoviiruste sugukonnaga. Seosele viitasid nii kapsiidivalgu L1 kui ka E1 valgu geen.
Viiruse genoomid on kompaktsed ning kodeeriva potentsiaali efektiivsemaks kasutamiseks võivad mõned geenid üksteisega kas osaliselt või täielikult kattuda. Üheks selliseks geeniks on E8, mis asub PV-de E1 geeni sees ja mida on eksperimentaalselt tuvastatud väga vähestes PV-des. Töö teise eesmärgina analüüsiti in silico üle 300 PV genoomi, tuvastamaks E8 olemasolu nende E1 geenides. E8 ei suudetud tuvastada ainult nendes PV-des, mis nakatavad roomajaid, linde ja kalu. Tulemused viitavad hilisemale E8 tekkele, pärast imetajate lahknemist teistest selgroogsetest.
Eelpool nimetatud topelt kodeeriva ala, aga ka paljude teiste geenisiseste elementide tuvastamine nõuab spetsiifilisi lahendusi. Kolmanda eesmärgina loodi antud doktoritöö käigus veebitööriist nimega cRegions [http://bioinfo.ut.ee/cRegions/], mis on võimeline tuvastama erinevaid funktsionaalseid elemente viiruste geenidest.
Viruses are obligatory intracellular parasites harbouring enormous genetic and biological diversity. Viruses are the most abundant biological entities on Earth. Unlike cellular organisms, viruses have multiple evolutionary origins. While there are many hypotheses how viruses emerged, their exact origin is still unknown. In the current thesis, papillomaviruses (PVs) were used as an example to study the potential origin of a viral family. PVs infect many mammalian species, but also birds, turtles, snakes, and fish. PVs have been of interest due to their association with various cancers. Oncogenic human papillomaviruses (HPVs) are responsible for almost all cases of cervical and anal cancers. In this thesis, various sequence collections were analysed to detect distant homologs to PV protein domains in other organisms. We found that PVs have very weak connections to cellular organisms, as only domains from the E1 replication protein had distant homologs in cellular organisms. However, our study revealed that PVs are evolutionarily related to Polyomaviridae and Parvoviridae family. Both of them shared structural homologs of capsid protein L1 and two domains of replication protein E1. Viral genomes mainly encode protein-coding genes. Occasionally, some of these genes are fully embedded inside one another. In this thesis, over 300 PV genomes were analysed in silico to detect an embedded gene called E8, located within the E1 gene. The E8 was detected in almost all PV-s, except PVs infecting Sauropsida and fish. As these hosts are evolutionarily older than mammalian species, it confirms that E8 emerged after the divergence of mammals. The detection of the dual-coding region E8 and other embedded elements needs specific solutions. In this thesis, a web tool called cRegions [http://bioinfo.ut.ee/cRegions/] was developed to detect overlapping genes and other embedded elements in protein-coding genes of viruses.
Viruses are obligatory intracellular parasites harbouring enormous genetic and biological diversity. Viruses are the most abundant biological entities on Earth. Unlike cellular organisms, viruses have multiple evolutionary origins. While there are many hypotheses how viruses emerged, their exact origin is still unknown. In the current thesis, papillomaviruses (PVs) were used as an example to study the potential origin of a viral family. PVs infect many mammalian species, but also birds, turtles, snakes, and fish. PVs have been of interest due to their association with various cancers. Oncogenic human papillomaviruses (HPVs) are responsible for almost all cases of cervical and anal cancers. In this thesis, various sequence collections were analysed to detect distant homologs to PV protein domains in other organisms. We found that PVs have very weak connections to cellular organisms, as only domains from the E1 replication protein had distant homologs in cellular organisms. However, our study revealed that PVs are evolutionarily related to Polyomaviridae and Parvoviridae family. Both of them shared structural homologs of capsid protein L1 and two domains of replication protein E1. Viral genomes mainly encode protein-coding genes. Occasionally, some of these genes are fully embedded inside one another. In this thesis, over 300 PV genomes were analysed in silico to detect an embedded gene called E8, located within the E1 gene. The E8 was detected in almost all PV-s, except PVs infecting Sauropsida and fish. As these hosts are evolutionarily older than mammalian species, it confirms that E8 emerged after the divergence of mammals. The detection of the dual-coding region E8 and other embedded elements needs specific solutions. In this thesis, a web tool called cRegions [http://bioinfo.ut.ee/cRegions/] was developed to detect overlapping genes and other embedded elements in protein-coding genes of viruses.
Description
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Keywords
papilloomiviirused, viirusvalgud, viirusgeneetika