Global patterns of genetic diversity and phylogeography of Echinococcus granulosus sensu stricto – a tapeworm species of significant public health concern
Kuupäev
2018-06-29
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Abstrakt
Tsüstiline ehhinokokoos (CE) on haigus, mida põhjustavad Echinococcus granulosus sensu lato (s. l.) kompleksi kuuluvad paelussid. Sellesse kompleksi kuuluvate liikide hulgas on E. granulosus sensu stricto (s. s.) eriti oluline, olles ülemaailmselt kõige laialdasemalt levinud ning ka kõige sagedasem CE tekitaja inimesel.
Kuigi liigi geneetilise struktuuri mõistmiseks oli läbi viidud mitmeid uurimustöid, esines olulisi lünki, kuna siiani oli kasutatud lühikesi mitokondriaalseid (mtDNA) järjestusi. Esiteks oli üheks kõige olulisemaks probleemiks E. granulosus s. s. mitokondriaalsete genotüüpide olemasolu ning eristamine. Teiseks, kuigi oli välja pakutud, et G1–G3 on mitogenoomi geneetilise sarnasuse alusel üks liik, ei olnud seda teaduslikult näidatud. Kolmandaks, senised geneetilise mitmekesisuse ning fülogeograafia analüüsid ei olnud võimaldanud mõista detailseid globaalseid mustreid vähese fülogeneetilise eristusvõime tõttu.
Käesolevas doktoritöös analüüsiti ülemaailmselt kogutud parasiidiproove sekveneerides mitokondri genoomi pea täies pikkuses ning kaasates analüüsi ka mitmed tuumalookused. Esiteks tegime kindlaks, et E. granulosus s. s. koosneb kahest mitokondriaalsest genotüübist G1 ning G3 ja näitasime, et G2 ei ole eraldi genotüüp. Teiseks tegime kindlaks, et G1 ning G3 võib lugeda üheks liigiks. Kolmandaks näitasime, et genotüüpide G1 ja G3 geneetiline mitmekesisus on kõrge ning globaalsed alampopulatsioonid on geneetiliselt vähe diferentseerunud. Seda on suure tõenäosusega mõjutanud intensiivne ülemaailmne loomakaubandus ning -transport. Fülogeograafilise analüüsi tulemused näitasid, et E. granulosus s. s. üheks olulisemaks ekspansiooni keskpunktiks on olnud Lähis-Ida piirkond, mis on hästi tuntud lamba, veise ja kitse kodustamise piirkonnana – kõik need liigid on ka olulised E. granulosus s. s. vaheperemehed.
Antud doktoritöö on aluseks tulevastele E. granulosus s. s. genotüüpide leviku, geneetilise mitmekesisuse ning fülogeograafia alastele analüüsidele.
Cystic echinococcosis (CE) is a disease caused by tapeworms within the species complex Echinococcus granulosus sensu lato (s. l.). Within this complex, E. granulosus sensu stricto (s. s.) is associated with the majority of human CE cases globally and thus merits particular attention. Although extensive research had been carried out on the genetic structure of this species, significant gaps still existed due to the use of relatively short mitochondrial DNA sequences so far. Firstly, one of the most pressing questions was the existence and distinction of E. granulosus s. s. mitochondrial genotypes. Secondly, despite the assumptions that the mitochondrial genotypes can be regarded as a distinct species, further analysis was required. Thirdly, analyses of the patterns of genetic diversity and phylogeography of E. granulosus s. s. had lacked sufficient phylogenetic power to reveal detailed insight. The present thesis addressed these issues by sequencing and analysing near-complete mtDNA sequences and several nuclear loci for a large panel of globally distributed E. granulosus s. s. samples. Firstly, we determined that E. granulosus s. s. comprises two clearly distinct mitochondrial genotypes G1 and G3, whereas G2 is not a valid genotype. Secondly, we confirmed that G1 and G3 can indeed be regarded as a single species. Thirdly, the analyses of the global patterns of genetic diversity and phylogeography of E. granulosus s. s. revealed high genetic variation within genotypes G1 and G3, coupled with low genetic differentiation between G1 and G3 subpopulations globally, which is likely the consequence of extensive global animal transport and trade. The phylogeographic analysis revealed the Middle East as the origin of a large-scale expansion of both genotypes. The new data that the present thesis presents underpins our fundamental understanding of the genetic make-up of E. granulosus s. s. and provides a strong basis for future research on this parasite.
Cystic echinococcosis (CE) is a disease caused by tapeworms within the species complex Echinococcus granulosus sensu lato (s. l.). Within this complex, E. granulosus sensu stricto (s. s.) is associated with the majority of human CE cases globally and thus merits particular attention. Although extensive research had been carried out on the genetic structure of this species, significant gaps still existed due to the use of relatively short mitochondrial DNA sequences so far. Firstly, one of the most pressing questions was the existence and distinction of E. granulosus s. s. mitochondrial genotypes. Secondly, despite the assumptions that the mitochondrial genotypes can be regarded as a distinct species, further analysis was required. Thirdly, analyses of the patterns of genetic diversity and phylogeography of E. granulosus s. s. had lacked sufficient phylogenetic power to reveal detailed insight. The present thesis addressed these issues by sequencing and analysing near-complete mtDNA sequences and several nuclear loci for a large panel of globally distributed E. granulosus s. s. samples. Firstly, we determined that E. granulosus s. s. comprises two clearly distinct mitochondrial genotypes G1 and G3, whereas G2 is not a valid genotype. Secondly, we confirmed that G1 and G3 can indeed be regarded as a single species. Thirdly, the analyses of the global patterns of genetic diversity and phylogeography of E. granulosus s. s. revealed high genetic variation within genotypes G1 and G3, coupled with low genetic differentiation between G1 and G3 subpopulations globally, which is likely the consequence of extensive global animal transport and trade. The phylogeographic analysis revealed the Middle East as the origin of a large-scale expansion of both genotypes. The new data that the present thesis presents underpins our fundamental understanding of the genetic make-up of E. granulosus s. s. and provides a strong basis for future research on this parasite.
Kirjeldus
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Märksõnad
echinococcosis, Echinococcus granulosus, genetic diversity, phylogeography