RESUMEN
Genomic imprinting-the non-equivalence of maternal and paternal genomes-is a critical process that has evolved independently in many plant and mammalian species1,2. According to kinship theory, imprinting is the inevitable consequence of conflictive selective forces acting on differentially expressed parental alleles3,4. Yet, how these epigenetic differences evolve in the first place is poorly understood3,5,6. Here we report the identification and molecular dissection of a parent-of-origin effect on gene expression that might help to clarify this fundamental question. Toxin-antidote elements (TAs) are selfish elements that spread in populations by poisoning non-carrier individuals7-9. In reciprocal crosses between two Caenorhabditis tropicalis wild isolates, we found that the slow-1/grow-1 TA is specifically inactive when paternally inherited. This parent-of-origin effect stems from transcriptional repression of the slow-1 toxin by the PIWI-interacting RNA (piRNA) host defence pathway. The repression requires PIWI Argonaute and SET-32 histone methyltransferase activities and is transgenerationally inherited via small RNAs. Remarkably, when slow-1/grow-1 is maternally inherited, slow-1 repression is halted by a translation-independent role of its maternal mRNA. That is, slow-1 transcripts loaded into eggs-but not SLOW-1 protein-are necessary and sufficient to counteract piRNA-mediated repression. Our findings show that parent-of-origin effects can evolve by co-option of the piRNA pathway and hinder the spread of selfish genes that require sex for their propagation.
Asunto(s)
Caenorhabditis , Impresión Genómica , ARN de Interacción con Piwi , Secuencias Repetitivas de Ácidos Nucleicos , Animales , Femenino , Masculino , Alelos , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Caenorhabditis/genética , Caenorhabditis/metabolismo , Cruzamientos Genéticos , Padre , Genoma/genética , Impresión Genómica/genética , Organismos Hermafroditas/genética , Histona Metiltransferasas/genética , Histona Metiltransferasas/metabolismo , Madres , Oocitos/metabolismo , ARN de Interacción con Piwi/genética , Biosíntesis de Proteínas , Secuencias Repetitivas de Ácidos Nucleicos/genética , ARN Mensajero/genética , Toxinas Biológicas/genética , Transcripción GenéticaRESUMEN
BACKGROUND: Recently we described two outbred mouse lines which have been selected for high fertility. These mouse models doubled the number of offspring per litter. OBJECTIVES: Although selected for a primarily female-trait of high fertility (increased litter size), we were interested whether also males of the fertility lines show differences within their reproductive organs. MATERIALS AND METHODS: We investigated males from two outbred mouse lines which have been selected for the phenotype "high fertility" for more than 170 generations. In the present study, we analysed the testicular cell type composition by flow cytometry. We further investigated the weights of reproductive organs, histomorphometry of testis as well as studied sperm motility parameters using a thermal stress assay as well as a sperm hyperactivation assay. RESULTS: Here, we describe that males of the fertility line (FL) 1 show an increased percentage of diploid cells within the testis. Flow cytometric analysis identified this enlarged cell population as Leydig cells. Testis weights were unaffected whereas the weights of seminal vesicles of FL1 and FL2 were increased compared to Ctrl bucks. FL2 males show decreased diameter of tubulus seminiferi and an enhanced spermatid/Sertoli cell index. Sperm motility parameters of FL1 and Ctrl males are initially indistinguishable but FL1 spermatozoa show a better performance in a thermal stress experiment over a 5 hours observation period. DISCUSSION: These data indicate that although selected for a primarily female-trait of high fertility also males from the fertility lines are effected by defined alterations in their reproductive organs. CONCLUSION: Some of these alterations are FL1-specific others are FL2-associated, indicating that different molecular strategies warrant the high-fertility phenotype on the female as well as on the male side.
