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

PLoS One. 2024 Oct 18;19(10):e0312303. doi: 10.1371/journal.pone.0312303. eCollection 2024.

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.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alu Elements* / genetics
  • Animals
  • Cercopithecidae / genetics
  • DNA Transposable Elements / genetics
  • Evolution, Molecular*
  • Factor IX* / genetics
  • Hemophilia B* / genetics
  • Humans
  • Male
  • Mutation
  • Platyrrhini / genetics
  • Polyadenylation

Substances

  • Factor IX
  • 3' Untranslated Regions
  • DNA Transposable Elements

Grants and funding

The author(s) received no specific funding for this work.