A transposable element prevents severe hemophilia B and provides insights into the evolution of new- and old world primates

verfasst von

Johannes Kopp, Alice Rovai, Michael Ott, Heiner Wedemeyer, Andreas Tiede, Hans Jürgen Böhmer, Tomas Marques, Jörg Langemeier, Jens Bohne, Simon Alexander Krooss

Abstract

Alu-elements comprise a large part of the human genome and some insertions have been shown to cause diseases. Here, we illuminate the protective role of an Alu-element in the 3’UTR of the human Factor 9 gene and its ability to ameliorate a poly(A) site mutation in a hemophilia B patient, preventing him from developing a severe disease. Using a minigene, we examined the disease-causing mutation and the modifying effect of the transposon in cellulo. Further, we simulated evolutionary scenarios regarding alternative polyadenylation before and after Alu insertion. A sequence analysis revealed that Old World monkeys displayed a highly conserved polyadenylation sites in this Alu-element, whereas New World monkeys lacked this motif, indicating a selective pressure. We conclude that this transposon has inserted shortly before the separation of Old and New World monkeys and thus also serves as a molecular landmark in primate evolution.

Organisationseinheit(en)

Institut für Geobotanik

Externe Organisation(en)

Charité - Universitätsmedizin Berlin
Max-Planck-Institut für molekulare Genetik (MPIMG)
Freie Universität Berlin (FU Berlin)
Medizinische Hochschule Hannover (MHH)
Universität Pompeu Fabra (UPF)

Typ

Artikel

Journal

PLOS ONE

Band

19

ISSN

1932-6203

Publikationsdatum

18.10.2024

Publikationsstatus

Veröffentlicht

Peer-reviewed

Ja

ASJC Scopus Sachgebiete

Allgemein

Ziele für nachhaltige Entwicklung

SDG 3 – Gute Gesundheit und Wohlergehen

Elektronische Version(en)

https://doi.org/10.1371/journal.pone.0312303 (Zugang: Offen)