RESUMEN
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.
Asunto(s)
Pollos , Células Germinativas , Humanos , Masculino , Animales , Ratones , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Pollos/genética , Pollos/metabolismo , Células Germinativas/metabolismo , Testículo/metabolismo , Elementos Transponibles de ADN/genética , ARN de Interacción con Piwi , Mamíferos/genéticaRESUMEN
We present our open-source pipeline for quickly enhancing open data sets with research-focused expansions and show its effectiveness on a cornerstone open data set released by the Cook County government in Illinois. The City of Chicago and Cook County were both early adopters of open data portals and have made a wide variety of data available to the public; we focus on the medical examiner case archive which provides information about deaths recorded by Cook County's Office of the Medical Examiner, including overdoses invaluable to substance use disorder research. Our pipeline derives key variables from open data and links to other publicly available data sets in support of accelerating translational research on substance use disorders. Our methods apply to location-based analyses of overdoses in general and, as an example, we highlight their impact on opioid research. We provide our pipeline as open-source software to act as open infrastructure for open data to help fill the gap between data release and data use.