Evolucija TDP-43 in njegovih psevdogenov pri sesalcih

Gnidovec, Luka (author), Župunski, Vera (mentor)

TDP-43 je RNA vezavni protein s številnimi pomembnimi funkcijami v vseh stopnjah procesiranja RNA. Pomembno vlogo igra tudi v patofiziologiji nekaterih nevrodegenerativnih bolezni, kot sta ALS in FTLD. Človeški gen, ki zapisuje za TDP-43, se imenuje TARDBP. Sestavljen je iz šestih eksonov in vmesnih intronov, po procesiranju pa lahko dobimo 8 različnih mRNA, od katerih ena zapisuje za TDP-43. TARDBP je evolucijsko precej ohranjen, kar kaže na pomembno funkcijo proteina TDP-43. Poleg gena TARDBP se v človeškem genomu nahaja še pet njegovih procesiranih psevdogenov. V diplomski nalogi smo proučili evolucijske odnose TDP-43 pri sesalcih. Evolucijsko drevo smo zgradili s pomočjo 66 zaporedij sesalskih ortologov mRNA TDP-43, saj so proteinska zaporedja preveč podobna. Ugotovili smo, da evolucija TDP-43 v veliki meri sovpada s privzeto filogenijo vrst, z nekaterimi izjemami. Poleg tega smo raziskali, kdaj v evoluciji je prišlo do nastanka procesiranih psevdogenov 1, 2, 3 in 8. Ugotovili smo, da so vsi ti psevdogeni ohranjeni pri človeku podobnih opicah in opicah starega sveta. Za psevdogen 1 lahko z zanesljivostjo trdimo, da je ohranjen tudi pri opicah novega sveta. To zelo verjetno drži tudi za psevdogen 2, medtem ko so pri psevdogenih 3 in 8 rezultati bolj nejasni.

• Language: Slovenian
• Keywords: TDP-43, filogenetska analiza, psevdogeni
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2020
• PID: 20.500.12556/RUL-119799
• COBISS.SI-ID: 32569091
• Publication date in RUL: 11.09.2020

Secondary language

• Language: English
• Title: Evolution of mammalian TDP-43 and its pseudogenes

Abstract

TDP-43 is an RNA-binding protein involved in all stages of RNA processing. It also plays an important role in pathophysiology of some neurodegenerative diseases including ALS and FTLD. The human gene encoding TDP-43 is TARDBP. It consists of six exons and five introns. After processing, there are eight possible mRNA variants, one of which encodes for TDP-43. In addition to TARDBP, there are five processed TDP-43 pseudogenes in human genome. We examined the phylogenetic relationships of mammalian TDP-43 orthologues. The evolutionary tree was based on mRNA sequences because protein sequences are too similar. We concluded that TDP-43 phylogeny is mostly analogous to the evolutionary relationships of mammalian species with a few exceptions. In addition, we also studied when the human TDP-43 pseudogenes 1, 2, 3 and 8 emerged during evolution. We established that all these pseudogenes are present in Old world monkeys and Apes. Pseudogene 1 is also conserved in New world monkeys. The same is likely true for pseudogene 2, while analyses of pseudogene 3 and 8 give unclear information on the origin of these two pseudogenes.

• Keywords: TDP-43, phylogenetic analysis, pseudogenes