ABSTRACT
Crossing over during meiotic prophase I is required for sexual reproduction in mice and contributes to genome-wide genetic diversity. Here we report on the characterization of an N-ethyl-N-nitrosourea-induced, recessive allele called mei4, which causes sterility in both sexes owing to meiotic defects. In mutant spermatocytes, chromosomes fail to congress properly at the metaphase plate, leading to arrest and apoptosis before the first meiotic division. Mutant oocytes have a similar chromosomal phenotype but in vitro can undergo meiotic divisions and fertilization before arresting. During late meiotic prophase in mei4 mutant males, absence of cyclin dependent kinase 2 and mismatch repair protein association from chromosome cores is correlated with the premature separation of bivalents at diplonema owing to lack of chiasmata. We have identified the causative mutation, a transversion in the 5' splice donor site of exon 1 in the mouse ortholog of Human Enhancer of Invasion 10 (Hei10; also known as Gm288 in mouse and CCNB1IP1 in human), a putative B-type cyclin E3 ubiquitin ligase. Importantly, orthologs of Hei10 are found exclusively in deuterostomes and not in more ancestral protostomes such as yeast, worms, or flies. The cloning and characterization of the mei4 allele of Hei10 demonstrates a novel link between cell cycle regulation and mismatch repair during prophase I.
Subject(s)
Cell Cycle Proteins/genetics , Crossing Over, Genetic/genetics , Meiotic Prophase I/genetics , Mutation , Ubiquitin-Protein Ligases/genetics , Adaptor Proteins, Signal Transducing , Alleles , Animals , Base Pair Mismatch/genetics , Cattle , Cell Cycle Proteins/physiology , Cyclin-Dependent Kinase 2/deficiency , Cyclin-Dependent Kinase 2/genetics , Cyclin-Dependent Kinase 2/metabolism , Female , Humans , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout , Recombination, Genetic , Ubiquitin-Protein Ligases/physiologyABSTRACT
Using the housefly, Musca domestica (L), as a model system, we tested the ability of two extrems in the range of possible captive breeding protocols to yield sustainable populations following founding with low founder numbers. The protocols tested included two levels of migration as well as inbreeding followed by selection, each with appropriate controls. Each low-founder-number population was founded with two pairs of flies. The maximum migration scheme had 50% migration per generation, and the minimum migration populations experienced a migration rate of 2.5% per generation. The control level of migration was 0%. A fourth low-founder-number treatment was designed to test the effect of inbreeding followed by selection. Two sets of high-founder-number control groups were also derived from the stock population. Two fitness measures, viability and productivity of the populations, were recorded at the fifth generation. Populations in the minimum-migration and zero migration treatment groups had lower fitness than populations in any other treatment for both measures. Populations that experienced inbreeding and selection for high fitness levels, high levels of migration, or large high-founder-number populations were equally fit. These results demonstrate that a captive-breeding scheme that contains substantial levels of migration or inbreeding followed by selection can yield highly adapted populations. Efecto de la migración o intracruza seguido por la selección de poblacions originadas a partir de un número pequeño de fundadores.
Resumen: En este trabajo usamos a la mosca doméstica Musca domestica (L.) como un sistema modelo para examinar la habilidad de dos extremos en el espectro posible de protocolos para obtener poblaciones sustentables de especies cautivas luego de un evento fundador con un número bajo de fundadores. Los protocolos examinados incluyeron dos níveles de migración, asi como también intracruza seguid de selección, cada uno con controles apropiados. Cada población originada a partir de un número bajo de fundadores por fue fundada por dos pares de moscas. El esquema de mayor migración tuvo una tasa de migración del 50% generación y el mínimo experimentó una tasa de migración del 2.5% por generación. El nivel control de migración fue del 0%. Un cuarto tratamiento con un bajo número de fundadores fue diseñado para examinar el efecto la intracruza seguido de selección. También se obtuvieron a partir de la población original dos juegos de grupos de control con un alto número de fundadores. En la quinta generación se registraron dos medidas la condicíon, la viabilidad y la productividad de las poblaciones. Las poblaciones en los grupos con immigración baja o nula tuvieron una condición más baja que las poblaciones en cualquiera de los otros tratamientos para ambas medidas de condición. Las poblaciones que experimentaron intracruza y selección para niveles de condición altos, niveles altos de migración o un número de fundadores alto tuvieron la misma condición. Estos resultados demuestran que un esquema de cría en cautiverio que incluya niveles substanciales de migración o intracruza seguido de selección puede producir poblaciones altamente adaptadas.
