In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication

The transition from mitosis to meiosis is a defining juncture in the life cycle of sexually reproducing organisms. In yeast, the decision to enter meiosis is made before the single round of DNA replication that precedes the two meiotic divisions. We present genetic evidence of an analogous decision point in the germ line of a multicellular organism. The mouse Stra8 gene is expressed in germ cells of embryonic ovaries, where meiosis is initiated, but not in those of embryonic testes, where meiosis does not begin until after birth. Here we report that in female embryos lacking Stra8 gene function, the early, mitotic development of germ cells is normal, but these cells then fail to undergo premeiotic DNA replication, meiotic chromosome condensation, cohesion, synapsis and recombination. Combined with previous findings, these genetic data suggest that active differentiation of ovarian germ cells commences at a regulatory point upstream of premeiotic DNA replication.     

Positive darwinian selection at the imprinted MEDEA locus in plants

In mammals and seed plants, a subset of genes is regulated by genomic imprinting where an allele's activity depends on its parental origin. The parental conflict theory suggests that genomic imprinting evolved after the emergence of an embryo-nourishing tissue (placenta and endosperm), resulting in an intragenomic parental conflict over the allocation of nutrients from mother to offspring. It was predicted that imprinted genes, which arose through antagonistic co-evolution driven by a parental conflict, should be subject to positive darwinian selection. Here we show that the imprinted plant gene MEDEA (MEA), which is essential for seed development, originated during a whole-genome duplication 35 to 85 million years ago. After duplication, MEA underwent positive darwinian selection consistent with neo-functionalization and the parental conflict theory. MEA continues to evolve rapidly in the out-crossing species Arabidopsis lyrata but not in the self-fertilizing species Arabidopsis thaliana, where parental conflicts are reduced. The paralogue of MEA, SWINGER (SWN; also called EZA1), is not imprinted and evolved under strong purifying selection because it probably retained the ancestral function of the common precursor gene. The evolution of MEA suggests a late origin of genomic imprinting within the Brassicaceae, whereas imprinting is thought to have originated early within the mammalian lineage.     

The Arabidopsis thaliana MEDEA Polycomb group protein controls expression of PHERES1 by parental imprinting

The maternally expressed Arabidopsis thaliana Polycomb group protein MEDEA (MEA) controls expression of the MADS-box gene PHERES1 (PHE1). Here, we show that PHE1 is mainly paternally expressed but maternally repressed and that this maternal repression of PHE1 breaks down in seeds lacking maternal MEA activity. Because Polycomb group proteins control parental imprinting in mammals as well, the independent recruitment of similar protein machineries for the imprinting of genes is a notable example of convergent evolution.     

Chromosome Y-specific DNA in related human XX males

Human 'XX males' are sterile males whose chromosomes seem to be those of a normal female. About 1 in 20,000 males has a 46, XX karyotype, and most cases are sporadic, that is, they are without familial clustering. It has long been argued that maleness in XX males may result from the undetected presence of a small, testis-determining fragment of the Y chromosome, and there is strong evidence for this in sporadically occurring XX males. Indeed, the genomes of three of four sporadic XX males tested were found to contain certain Y-specific DNA sequences. A pedigree in which three XX males occur has been interpreted as being consistent with autosomal recessive inheritance of maleness, and it has been argued that the basis of XX maleness in this family is fundamentally different from that in the sporadic cases. However, we report here that these related XX males, like the sporadic cases, contain portions of the Y chromosome. The portion of the Y chromosome present in one of the three XX males differs from that present in the other two.     

Lymphocyte-fibroblast interaction in the pathogenesis of inflammatory gingival disease

Zusammenfassung Eine morphometrische Analyse menschlicher, entzündeter Gingiva ergab im Vergleich zu normalem Bindegewebe 70% weniger Kollagenfasern, dreifach vergrösserte und pathologisch veränderte Fibroblasten und eine kleine Population charakteristischer Immunoblasten mit einer Zellansammlung, die zu 76% aus Zellen der Lymphozytenserie bestand. Die Grösse der Fibroblasten war positiv mit der steigenden Zahl der Lymphozyten korreliert. Diese Befunde weisen auf eine Immunreaktion mit zytotoxischen Auswirkungen auf Fibroblasten des gingivalen Bindegewebes hin.     

Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia

Pre-eclampsia is a principal cause of maternal morbidity and mortality, affecting 5-10% of first pregnancies worldwide. Manifestations include increased blood pressure, proteinuria, coagulopathy and peripheral and cerebral oedema. Although the aetiology and pathogenesis remain to be elucidated, the placenta is undoubtedly involved, as termination of pregnancy eradicates the disease. Here we have cloned a complementary DNA from human placental messenger RNA encoding a precursor protein of 121 amino acids which gives rise to a mature peptide identical to the neuropeptide neurokinin B (NKB) of other mammalian species. In female rats, concentrations of NKB several-fold above that of an animal 20 days into pregnancy caused substantial pressor activity. In human pregnancy, the expression of NKB was confined to the outer syncytiotrophoblast of the placenta, significant concentrations of NKB could be detected in plasma as early as week 9, and plasma concentrations of NKB were grossly elevated in pregnancy-induced hypertension and pre-eclampsia. We conclude that elevated levels of NKB in early pregnancy may be an indicator of hypertension and pre-eclampsia, and that treatment with certain neurokinin receptor antagonists may be useful in alleviating the symptoms.     

Unexpectedly similar rates of nucleotide substitution found in male and female hominids

In 1947, it was suggested that, in humans, the mutation rate is dramatically higher in the male germ line than in the female germ line. This hypothesis has been supported by the observation that, among primates, Y-linked genes evolved more rapidly than homologous X-linked genes. Based on these evolutionary studies, the ratio (alpha(m)) of male to female mutation rates in primates was estimated to be about 5. However, selection could have skewed sequence evolution in introns and exons. In addition, some of the X-Y gene pairs studied lie within chromosomal regions with substantially divergent nucleotide sequences. Here we directly compare human X and Y sequences within a large region with no known genes. Here the two chromosomes are 99% identical, and X-Y divergence began only three or four million years ago, during hominid evolution. In apes, homologous sequences exist only on the X chromosome. We sequenced and compared 38.6 kb of this region from human X, human Y, chimpanzee X and gorilla X chromosomes. We calculated alpha(m) to be 1.7 (95% confidence interval 1.15-2.87), significantly lower than previous estimates in primates. We infer that, in humans and their immediate ancestors, male and female mutation rates were far more similar than previously supposed.