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

authored by

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.

Organisation(s)

Institute of Geobotany

External Organisation(s)

Charité - Universitätsmedizin Berlin
Max Planck Institute for Molecular Genetics (MPIMG)
Freie Universität Berlin (FU Berlin)
Hannover Medical School (MHH)
Universität Pompeu Fabra (UPF)

Type

Article

Journal

PLOS ONE

Volume

19

ISSN

1932-6203

Publication date

18.10.2024

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

General

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1371/journal.pone.0312303 (Access: Open)