Amniotes co-opt intrinsic genetic instability to protect germ-line genome integrity

Nat Commun. 2023 Feb 13;14(1):812. doi: 10.1038/s41467-023-36354-x.

Abstract

Unlike PIWI-interacting RNA (piRNA) in other species that mostly target transposable elements (TEs), >80% of piRNAs in adult mammalian testes lack obvious targets. However, mammalian piRNA sequences and piRNA-producing loci evolve more rapidly than the rest of the genome for unknown reasons. Here, through comparative studies of chickens, ducks, mice, and humans, as well as long-read nanopore sequencing on diverse chicken breeds, we find that piRNA loci across amniotes experience: (1) a high local mutation rate of structural variations (SVs, mutations ≥ 50 bp in size); (2) positive selection to suppress young and actively mobilizing TEs commencing at the pachytene stage of meiosis during germ cell development; and (3) negative selection to purge deleterious SV hotspots. Our results indicate that genetic instability at pachytene piRNA loci, while producing certain pathogenic SVs, also protects genome integrity against TE mobilization by driving the formation of rapid-evolving piRNA sequences.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chickens* / genetics
  • Chickens* / metabolism
  • DNA Transposable Elements / genetics
  • Germ Cells* / metabolism
  • Humans
  • Male
  • Mammals / genetics
  • Mice
  • Piwi-Interacting RNA
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Testis / metabolism

Substances

  • RNA, Small Interfering
  • DNA Transposable Elements
  • Piwi-Interacting RNA