Biomedical subjects
Publications and source records attributed to J H Hackstein.
The Y chromosomes of Drosophila are necessary for male fertility. They carry giant genes that have some unconventional properties besides controlling the motility of the spermatozoa. Classical genetic and molecular studies suggest that evolution has favoured the close association between these genes and repetitive DNA sequences with 'selfish' traits.
The presence of significant numbers of intestinal methanogens among vertebrates does neither depend on elaborated morphological structures nor on predominantly plant-based diets. Phylogenetic rather than dietary restrictions limit the occurrence of methanogenic bacteria also in the hindguts of primates. The Old-World monkeys are methanogenic--with the only exceptions of Cheirogaleid lemurs and bush-babies. In contrast, among New World monkeys the lack of intestinal methanogens is observed frequently in capuchins and marmosets. Since the absence of methanogens does not parallel distinct morphological, physiological, or ethological characteristics, it is likely that methanogenesis depends on a hereditary predisposition. In humans, methane-producers account for approximately 50% of the European populations. In this study, 56 individuals belonging to 5 families were studied for the occurrence of methane in the breath. The results of this screen are compatible with the assumption that the trait "methane emission" segregates as an autosomal, dominant character. Our findings suggest a high specificity of the symbiosis between primates and methanogenic bacteria. Therefore, the persistence of significant numbers of methanogens in the hindgut might be facilitated by a specific receptor for methanogenic bacteria.
We have screened more than 110 representatives of the different taxa of terrestrial arthropods for methane production in order to obtain additional information about the origins of biogenic methane. Methanogenic bacteria occur in the hindguts of nearly all tropical representatives of millipedes (Diplopoda), cockroaches (Blattaria), termites (Isoptera), and scarab beetles (Scarabaeidae), while such methanogens are absent from 66 other arthropod species investigated. Three types of symbiosis were found: in the first type, the arthropod's hindgut is colonized by free methanogenic bacteria; in the second type, methanogens are closely associated with chitinous structures formed by the host's hindgut; the third type is mediated by intestinal anaerobic protists with intracellular methanogens. Such symbiotic associations are likely to be a characteristic property of the particular taxon. Since these taxa represent many families with thousands of species, the world populations of methane-producing arthropods constitute an enormous biomass. We show that arthropod symbionts can contribute substantially to atmospheric methane.
The eye color mutant prune (pn) of Drosophila melanogaster shows a lethal interaction with the Killer-of-prune (K-pn) allele of the abnormal wing disc (awd) locus. The awd gene is the Drosophila homologue of the mammalian tumor metastasis gene nm23, and it has been postulated that pn encodes a protein with similarity to a GAP, a GTPase-activating protein. Such GAPs potentially control Ras-like proteins, which are important molecular switches. However, there is only a low sequence homology with the genes for human GAP and neurofibromatosis (NF1), and with yeast IRA1 and IRA2, and there is no evidence for the functional significance of this homologization. I now show that pn mutations lower the concentrations of larval pteridines, and that this phenomenon is enhanced by two orders of magnitude by the lethal interaction between pn and awdK-pn. These gradual effects on the pteridin concentrations indicate a corresponding drop of the pools of free GTP, and favor the involvement of GTP-binding proteins. In addition, cytology reveals a considerable hypertrophy of the neuroglia and the perineurium of the larval brain. Furthermore, the lymph glands of the larvae are highly abnormal and form melanotic (pseudo)tumors upon ageing of the larvae. These pseudotumors consist predominantly of lamellocytes which are part of the cellular defence system of Drosophila. These observations most likely indicate hyperactivity of a Ras-like protein which becomes manifest in cell types equivalent to the cell types affected by human neurofibromatosis (NF1). Thus, it is very suggestive to regard the synthetic lethal system prune/Killer-of-prune as the Drosophila model for human neurofibromatosis.
Two competing hypotheses have been proposed for the function of the Y chromosomal fertility factors in Drosophila, which form giant lampbrush loops during the primary spermatocyte stage. The first hypothesis suggests a conventional coding function, the second proposes an unconventional gene function mediated through protein binding by nascent transcripts. Therefore, we studied the genetics and cytogenetics of the two Y chromosomal fertility genes A and C of Drosophila hydei (which form the lampbrush loops threads and pseudonucleolus) in order to test the validity of these different hypotheses. Both lampbrush loops bind specific proteins, which are recognized by different antisera. Absence of either of the lampbrush loops does not interfere with the synthesis of the antigens but completely prevents the binding of the particular antigen to other lampbrush loops. Absence of the loops also does not interfere with the postmeiotic presence and localization of the particular antigen. Deletion (or inactivation) of either of the lampbrush loops threads or pseudonucleolus causes sterility of the male flies as do other male-sterile alleles of both fertility genes, which do not affect the morphology of the lampbrush loops. The phenotypic effects of these mutations on sperm morphogenesis are identical for all various male-sterile alleles of each of the fertility genes A and C, regardless of whether a particular allele leaves the loop intact, modifies that loop, or deletes (or inactivates) the loop completely. Finally, the isolation of fertile Y chromosomal mutations which modify the morphology of the lampbrush loops demonstrates that it is possible to uncouple loop morphology and genetic function. These findings do not support the hypothesis that the binding of proteins to a lampbrush loop has a substantial impact on spermiogenesis.
Y chromosomal fertility genes are essential for spermatogenesis, but those genes which code for major structural components of the spermatozoon and those controlling sperm morphogenesis must be located on a different chromosome. In the past, it had been questioned whether it would be possible to achieve a meaningful classification of male sterile mutations by light microscopy. I now show, however, that comparison of 244 autosomal male sterile mutants of Drosophila hydei with 400 similar mutants in D. melanogaster not only allows such a classification on the basis of the apparent targets, but also permits a genetic dissection of sperm morphogenesis. Differentiation of male germ cells is best characterized as spermeoteleosis, since male sterile mutations have the effect of aborting spermatogenesis rather than changing the cellular fate of the germ cells. In contrast to earlier proposals concerning sequential determinative events during this process, male sterile mutations can block spermatogenesis at nearly every stage, and not, as previously postulated, exclusively at the transitions between gonial, meiotic, and postmeiotic stages. Male sterile mutations can modify the topology of the organelles of a spermatid, and they can also affect the different components (i.e., nucleus, axoneme, nebenkern) of a germ cell to quite different degrees, leading to characteristic pleiotropic phenotypes. Some male sterile mutations can decouple the development of the different components of a germ cell, i.e., they may lead to a heterochrony of the development of the different subcellular structures, or they may permit the differentiation of some components of a germ cell even in the complete absence of an organelle. Thus, it is possible to describe spermatogenesis as the concerted, but not interdependent, execution of separate developmental programs for the particular components of male germ cells.
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By immunofluorescence techniques and protein blotting experiments we have shown that an antiserum specifically reacts with a Mr 80,000 protein (the "Ps protein") in the lampbrush loop " pseudonucleolus " in spermatocyte nuclei of Drosophila hydei. Comparative studies of X/Y and X/0 testes indicate that the gene encoding the Ps protein is not located on the Y chromosome but on an autosome or the X chromosome. The Ps protein is tissue specific. It is likely to be a rather conserved protein since the antigenic determinant recognized by the antiserum could be detected in the spermatocyte nuclei of a number of other Drosophila species. For those species with prominent Y chromosomal lampbrush loops, it could be shown that the cross-reaction is, as in D. hydei, associated with a specific Y chromosomal loop.
A comparative study of the protein patterns in testes of wild-type and X/O flies of Drosophila hydei revealed quantitative differences in at least three major protein fractions. One protein component of a Mr 155,000 fraction and a protein of Mr 35,000 are completely absent in X/O testes. The amount of protein in a Mr 55,000 fraction is considerably reduced. The tubulins, which are part of this fraction, are also reduced in amount. All three proteins were found as constituents of sperm tails. Studies of Y chromosomal mutants revealed that the presence of at least two of these proteins depends on the activity of loci O, P, and Q of the Y chromosome. However, preliminary evidence indicates an autosomal location of the genes of these sperm proteins. This suggests a regulatory role of Y chromosomal genes in the production of some major sperm proteins.
A genetic map of the Y chromosome of Drosophila hydei has been constructed from deletion/complementation experiments, with the aid of male sterile mutants of the Y chromosome. A central conclusion of our experiments is that not more than a single complementation group can be detected in each of the lampbrush loop forming sites. Additional complementation groups, functionally independent of lampbrush loops, reside between these loci. Six complementation groups have been defined by several methods of mapping. An additional ten complementation groups are indicated, but their exact definition requires further investigation. The "synthetic sterility" of mutations in these ten loci contributes to the difficulty in unequivocally establishing their individual boundaries. Mapping problems also arise from the instability of certain mutants.
Aerobic and anaerobic ciliates swim towards the cathode when they are exposed to a constant DC field. Nyctotherus ovalis from the intestinal tract of cockroaches exhibits a different galvanotactic response: at low strength of the DC field the ciliates orient towards the anode whereas DC fields above 2-4 V/cm cause cathodic swimming. This reversal of the galvanotactic response is not due to backward swimming. Rather the ciliates turn around and orient to the cathode with their anterior pole. Exposure to various cations, chelators, and Ca(2+)-channel inhibitors suggests that Ca(2+)-channels similar to the "long lasting" Ca(2+)-channels of vertebrates are involved in the voltage-dependent anodic galvanotaxis. Evidence is presented that host-dependent epigenetic factors can influence the voltage-threshold for the switch from anodic to cathodic swimming.