The pachytene checkpoint

The pachytene checkpoint prevents meiotic nuclear division in cells that fail to complete meiotic recombination and chromosome synapsis. This control mechanism prevents chromosome missegregation that would lead to the production of aneuploid gametes. The pachytene checkpoint requires a subset of proteins that function in the mitotic DNA damage checkpoint. In budding yeast, the pachytene checkpoint also requires meiosis-specific chromosomal proteins and, unexpectedly, proteins concentrated in the nucleolus. Progress has been made in identifying components of the cell-cycle machinery that are impacted by the checkpoint.     

转基因雄性不育系及其在杂种种子生产上的应用

雄性不育为农作物杂种优势的利用开辟了一条经济有效的途径。本综述了利用生物技术培育转基因雄性不育的多种策略,以及繁育用作大田配制杂交种的母本雄性不育系的新方法;探讨了其应用于商业化杂种生产的重要性及前景。     

DNA methylation patterns of human pachytene spermatocytes

A study has been made of the possibility that methylation occurs during germ cell production in the human testis. Utilizing the immunoperoxidase method with an antibody to 5-methylcytidine, it has been demonstrated that the number of immunoreactive sites on bivalents increased between early and mid/late pachytene.     

Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin activation

Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea and eukaryotes, including humans. Genetic deficiencies of enzymes involved in Moco biosynthesis in humans lead to a severe and usually fatal disease. Moco contains a tricyclic pyranopterin, termed molybdopterin (MPT), that bears the cis-dithiolene group responsible for molybdenum ligation. The dithiolene group of MPT is generated by MPT synthase, which consists of a large and small subunits. The 1.45 A resolution crystal structure of MPT synthase reveals a heterotetrameric protein in which the C-terminus of each small subunit is inserted into a large subunit to form the active site. In the activated form of the enzyme this C-terminus is present as a thiocarboxylate. In the structure of a covalent complex of MPT synthase, an isopeptide bond is present between the C-terminus of the small subunit and a Lys side chain in the large subunit. The strong structural similarity between the small subunit of MPT synthase and ubiquitin provides evidence for the evolutionary antecedence of the Moco biosynthetic pathway to the ubiquitin dependent protein degradation pathway.     

A disruption of pachytene DNA metabolism in male mice with chromosomally-derived sterility

DNA metabolism was analyzed in spermatocytes of mice that were sterile either because of X-autosome or autosome-autosome translocations, or because of trisomy. In the strains analyzed, spermatogenic development is arrested by metaphase I or soon thereafter. In all such strains, a disruption of the normal pattern of pachytene DNA metabolism occurred. Prepachytene metabolism appeared normal. Disruption was manifest in both the level of endogenously generated nicks during pachytene and in the distribution of nicks among the different DNA sequence classes. Nicking was more intense in the steriles and tended to be randomized in distribution. Satellite DNA underwent pachytene nick-repair in the steriles but not in fertile controls. The repair capacity of spermatocytes from steriles was equal to that of the fertiles; the higher frequency of nicks in the steriles was due to a persistence of nicking activity.     

Epistasis and hybrid sterility in Saccharomyces

Hybrid sterility is thought to be due to deleterious epistatic interactions between genes from different species. Here we demonstrate that dominant genic incompatibility does not contribute to sterility in hybrids between Saccharomyces cerevisiae and five closely related species. Sterile diploids were made fertile by genome doubling to produce hybrid tetraploids. Based on these and previous results, we conclude that neither genic incompatibility nor classical chromosomal speciation models apply.     

Cytoplasmic male sterility in relation to hybrid wheat breeding

Summary The method of substitution and restoration of nucleus is briefly described.Three species, Aegilops caudata, Ae. ovata and Triticum timopheevi, were used as donors of male sterility cytoplasms.The characteristics of these three cytoplasms are summarized as follows:Caudata-cytoplasm: This cytoplasm has in many respects deleterious effects on the manifestation of alien genomes. Substitution lines having hexaploid wheat genome constitution are mostly male sterile while the female organ is normal. Some lines set frequently germless seeds. Haploid and twin seedlings are of common occurrence in other lines. Pistillody is common in the substitution lines with tetraploid wheat genomes.Ovata-cytoplasm: No pistillody was found in the substitution lines, both with hexaploid and tetraploid wheats. Male sterility is always complete in the substitution lines of hexaploid wheats with the exception of P 168, a variety of common wheat having a pair of satchromosomes of Ae. caudata. This variety restores male fertility completely. No effective restorers were found for the substitution lines of emmer wheat. Delayed heading is common in the 4x substitution lines.Timopheevi-cytoplasm: Substitution lines of 6x wheats are mostly male sterile, while those of 4x wheats are more or less male fertile. Only the genome of T. spelta duhamelianum restores completely pollen fertility.Among the indispensable factors for the success of hybrid wheat, five were discussed. They were (1) hetero sis, (2) selection of male sterile cytoplasms, (3) discovery of restoring genes, (4) production of hybrid seeds and (5) quality.

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Zusammenfassung Die Methode der Substitution und Restoration des Nucleus wird kurz beschrieben.Drei Arten, Aegilops caudata, Ae. ovata und Triticum timopheevi, wurden als Donor cytoplasmatisch bedingter männlicher Sterilität verwendet. Die Charakteristika der jeweiligen Cytoplasmen lassen sich wie folgt zusammenfassen:Caudata-Cytoplasma: Dieses Cytoplasma hat in vieler Hinsicht einen schädlichen Einfluß auf die Manifestation fremder Genome. Substitutionslinien mit einem hexaploiden Weizengenom sind meist männlich steril, das weibliche Organ ist normal. Einige Linien bringen häufig keimlose Samen; in anderen Linien treten haploide und Zwillingssamen auf. Bei Substitutionslinien mit tetraploiden Weizengenomen werden häufig andere Blütenorgane in Karpelle umgewandelt.Ovata-Cytoplasma: In den Substitutionslinien sowohl der hexaploiden wie tetraploiden Weizen wurden keine anderen Blütenorgane in Karpelle umgewandelt. Die Substitutionslinien der hexaploiden Weizen sind stets vollkommen männlich steril mit Ausnahme von P 168, einer Weizenvarietät, die ein Paar Sat-Chromosomen von Ae. caudata besitzt. Diese Varietät stellt die männliche Fertilität vollkommen wieder her. In den Emmer-Substitutionslinien wurden keine wirksamen Restorer gefunden. Bei den 4x-Substitutionslinien zeigt sich häufig verzögertes Ährenschieben.Timopheevi-Cytoplasma: Die Substitutionslinien der 6x-Weizen sind meist männlich steril, die von 4x-Weizen dagegen mehr oder weniger männlich fertil. Nur das Genom von T. spelta duhamelianum stellt die Pollenfertilität völlig wieder her.Von den für den Erfolg der Hybridweizenzüchtung unabdingbaren Faktoren wurden die folgenden 5 besprochen: 1. Heterosis, 2. Selektion männliche Sterilität bedingender Cytoplasmen, 3. Auffinden von Restorergenen, 4. Produktion von Hybridsaatgut und 5. Qualität.

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Dedicated to Professor Hans Stubbe on the occasion of his 65^th birthday.

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Contribution from the National Institute of Genetics, Japan, No. 636. This paper has been prepared for a lecture delivered July 18, 1966, at the Lenin All-Union Academy of Agricultural Science. This work has been supported by the Rockefeller Foundation, Grant GA AGR 65111.     

The contribution of the y chromosome to hybrid male sterility in house mice

Hybrid sterility in the heterogametic sex is a common feature of speciation in animals. In house mice, the contribution of the Mus musculus musculus X chromosome to hybrid male sterility is large. It is not known, however, whether F(1) male sterility is caused by X-Y or X-autosome incompatibilities or a combination of both. We investigated the contribution of the M. musculus domesticus Y chromosome to hybrid male sterility in a cross between wild-derived strains in which males with a M. m. musculus X chromosome and M. m. domesticus Y chromosome are partially sterile, while males from the reciprocal cross are reproductively normal. We used eight X introgression lines to combine different X chromosome genotypes with different Y chromosomes on an F(1) autosomal background, and we measured a suite of male reproductive traits. Reproductive deficits were observed in most F(1) males, regardless of Y chromosome genotype. Nonetheless, we found evidence for a negative interaction between the M. m. domesticus Y and an interval on the M. m. musculus X that resulted in abnormal sperm morphology. Therefore, although F(1) male sterility appears to be caused mainly by X-autosome incompatibilities, X-Y incompatibilities contribute to some aspects of sterility.     

Binucleation and polyploidization patterns in developmental and regenerative rat liver growth

The hepatocellular binucleation rate, measured as the percentage of binuclear cells amongst newly formed bromodeoxyuridine-labelled and immunostained collage-nase-isolated rat hepatocytes, decreased from 12% to 4% between days 30 and 40 after birth, rose to 20% between days 50 and 60, and then declined again to the adult rate of about 10% at day 80. During regenerative growth following a two-thirds partial hepatectomy, the rate of binucleation declined to about 3%, causing the fraction of binuclear cells to fall from 27% (before hepactectomy) to 5% (at 45 h after hepactectomy) as pre-existing binuclear cells replicated and formed mononuclear daughter cells. Essentially all (97%) hepatocytes replicated at least once, starting their DNA synthesis at around 13 h and reaching a peak at 30 h, irrespective of ploidy and nuclearity. At later time points, the diploid hepatocytes had a higher labelling index than the polyploid cells, suggesting a greater tendency to go through several cell cycles.     

Molecular mechanisms of hybrid sterility in rice

Hybrid sterility presents a major bottleneck in hybrid crop breeding and causes postzygotic reproductive isolation in speciation.Here, we summarize the current understanding of the genetics of rice hybrid sterility and highlight new advances in deciphering the molecular basis of the major genetic loci for hybrid sterility in rice. We also discuss practical strategies for overcoming reproductive barriers to utilize hybrid vigor in inter-specific and inter-subspecific hybrid rice breeding.     

The mismatch repair system contributes to meiotic sterility in an interspecific yeast hybrid.

The mismatch repair system is the major barrier to genetic recombination during interspecific sexual conjugation in prokaryotes. The existence of this anti-recombination activity has implications for theories of evolution and the isolation of species. To determine if this phenomenon occurs in eukaryotes, the effect of a deficiency of mismatch repair on the meiotic sterility of an interspecific hybrid of Saccharomyces cerevisiae and the closely related species Saccharomyces paradoxus was examined. The results demonstrate that the rare viable spores from these hybrids have high frequencies of aneuploidy and low frequencies of genetic exchange. Hybrids lacking mismatch repair genes PMS1 or MSH2 display increased meiotic recombination, decreased chromosome non-disjunction and improved spore viability. These observations are consistent with the proposal that the mismatch repair system is an element of the genetic barrier between eukaryotic species. We suggest that an anti-recombination activity during meiosis contributes towards the establishment of post-zygotic species barriers.     

The use of evolutionary patterns in protein annotation

With genomic data skyrocketing, their biological interpretation remains a serious challenge. Diverse computational methods address this problem by pointing to the existence of recurrent patterns among sequence, structure, and function. These patterns emerge naturally from evolutionary variation, natural selection, and divergence--the defining features of biological systems--and they identify molecular events and shapes that underlie specificity of function and allosteric communication. Here we review these methods, and the patterns they identify in case studies and in proteome-wide applications, to infer and rationally redesign function.