Showing papers in "Annual Review of Genetics in 1999"

Meiotic chromosomes: integrating structure and function.

Abstract: ▪ Abstract Meiotic chromosomes have been studied for many years, in part because of the fundamental life processes they represent, but also because meiosis involves the formation of homolog pairs, ...

Fas ligand-induced apoptosis.

Abstract: The immune response is regulated not only by cell proliferation and differentiation, but also by programmed cell death, or apoptosis. In response to various stimuli, death factors bind to their respective receptors and activate the apoptotic death program in target cells. A cascade of specific proteases termed caspases mediates the apoptotic process. The activated caspases cleave various cellular components, a process that leads to morphological changes of the cells and nuclei, as well as to degradation of the chromosomal DNA. Loss-of-function mutations in the signaling molecules involved in apoptosis cause hyper-proliferation of cells in mouse and human. In contrast, exaggeration of this death cascade causes the destruction of various tissues.

Ribosome synthesis in Saccharomyces cerevisiae.

Abstract: The synthesis of ribosomes is one of the major metabolic pathways in all cells. In addition to around 75 individual ribosomal proteins and 4 ribosomal RNAs, synthesis of a functional eukaryotic ribosome requires a remarkable number of trans-acting factors. Here, we will discuss the recent, and often surprising, advances in our understanding of ribosome synthesis in the yeast Saccharomyces cerevisiae. These will underscore the unexpected complexity of eukaryotic ribosome synthesis.

Mitochondrial Genome Evolution and the Origin of Eukaryotes

Abstract: ▪ Abstract Recent results from ancestral (minimally derived) protists testify to the tremendous diversity of the mitochondrial genome in various eukaryotic lineages, but also reinforce the view that mitochondria, descendants of an endosymbiotic α-Proteobacterium, arose only once in evolution. The serial endosymbiosis theory, currently the most popular hypothesis to explain the origin of mitochondria, postulates the capture of an α-proteobacterial endosymbiont by a nucleus-containing eukaryotic host resembling extant amitochondriate protists. New sequence data have challenged this scenario, instead raising the possibility that the origin of the mitochondrion was coincident with, and contributed substantially to, the origin of the nuclear genome of the eukaryotic cell. Defining more precisely the α-proteobacterial ancestry of the mitochondrial genome, and the contribution of the endosymbiotic event to the nuclear genome, will be essential for a full understanding of the origin and evolution of the eukaryoti...

Mammalian DNA Mismatch Repair

Abstract: DNA mismatch repair (MMR) is one of multiple replication, repair, and recombination processes that are required to maintain genomic stability in prokaryotes and eukaryotes. In the wake of the discoveries that hereditary nonpolyposis colorectal cancer (HNPCC) and other human cancers are associated with mutations in MMR genes, intensive efforts are under way to elucidate the biochemical functions of mammalian MutS and MutL homologs, and the consequences of defects in these genes. Genetic studies in cultured mammalian cells and mice are proving to be instrumental in defining the relationship between the functions of MMR in mutation and tumor avoidance. Furthermore, these approaches have raised awareness that MMR homologs contribute to DNA damage surveillance, transcription-coupled repair, and recombinogenic and meiotic processes.

Messenger RNA stability and its role in control of gene expression in bacteria and phages.

Abstract: ▪ Abstract The stability of mRNA in prokaryotes depends on multiple factors and it has not yet been possible to describe the process of mRNA degradation in terms of a unique pathway. However, important advances have been made in the past 10 years with the characterization of the cis-acting RNA elements and the trans-acting cellular proteins that control mRNA decay. The trans-acting proteins are mainly four nucleases, two endo- (RNase E and RNase III) and two exonucleases (PNPase and RNase II), and poly(A) polymerase. RNase E and PNPase are found in a multienzyme complex called the degradosome. In addition to the host nucleases, phage T4 encodes a specific endonuclease called RegB. The cis-acting elements that protect mRNA from degradation are stable stem-loops at the 5′ end of the transcript and terminators or REP sequences at their 3′ end. The rate-limiting step in mRNA decay is usually an initial endonucleolytic cleavage that often occurs at the 5′ extremity. This initial step is followed by directional...

Molecular Genetics of Human Retinal Disease

Abstract: ▪ Abstract The past decade has witnessed extraordinary progress in retinal disease gene identification, the analysis of animal and tissue culture models of disease processes, and the integration of this information with clinical observations and with retinal biochemistry and physiology. During this period over twenty retinal disease genes were identified and for many of these genes there are now significant insights into their role in disease. This review presents an overview of the basic and clinical biology of the retina, summarizes recent progress in understanding the molecular mechanisms of inherited retinal diseases, and offers an assessment of the role that genetics will play in the next phase of research in this area.

Mechanisms of mRNA surveillance in eukaryotes.

Abstract: ▪ Abstract A conserved mRNA degradation system, referred to as mRNA surveillance, exists in eukaryotic cells to degrade aberrant mRNAs. A defining aspect of aberrant transcripts is that the spatial relationship between the termination codon and specific downstream sequence information has been altered. A key, yet unknown, feature of the mRNA surveillance system is how this spatial relationship is assessed in individual transcripts. Two views have emerged to describe how discrimination between proper and improper termination might occur. In the first view, a surveillance complex assembles onto the mRNA after translation termination, and scans the mRNA in a 3′ to 5′ direction for a limited distance. If specific downstream sequence information is encountered during this scanning, then the surveillance complex targets the transcript for rapid decay. An alternate view suggests that the downstream sequence information influences how translation termination occurs. This view encompasses several ideas including: ...

Mechanisms of Stationary Phase Mutation: A Decade of Adaptive Mutation

Abstract: ▪ Abstract A decade of research on adaptive mutation has revealed a plethora of mutagenic mechanisms that may be important in evolution. The DNA synthesis associated with recombination could be an important source of spontaneous mutation in cells that are not proliferating. The movement of insertion elements can be responsive to environmental conditions. Insertion elements not only activate and inactivate genes, they also provide sequence homology that allows large-scale genomic rearrangements. Some conjugative plasmids can recombine with their host's chromosome, and may acquire chromosomal genes that could then spread through the population and even to other species. Finally, a subpopulation of transient hypermutators could be a source of multiple variant alleles, providing a mechanism for rapid evolution under adverse conditions.

Genetics of chemotaxis and thermotaxis in the nematode Caenorhabditis elegans.

Abstract: ▪ Abstract Molecular genetic analysis of chemotaxis and thermotaxis in Caenorhabditis elegans has revealed the molecular bases of olfaction, taste, and thermosensation, which, in turn, has demonstrated that sensory signaling in C. elegans is very similar to that in vertebrates. A cyclic nucleotide-gated channel (TAX-2/TAX-4) that is highly homologous to the olfactory and photoreceptor channels in vertebrates is required for taste and thermosensation, in addition to olfaction. A cation channel (OSM-9) that is closely related to a capsaicin receptor channel is required for olfactory adaptation in one olfactory neuron and olfactory sensation in the other olfactory neuron. A novel Gα protein (ODR-3) is essential for olfactory responses in all olfactory neurons and aversive responses in a polymodal sensory neuron. A G protein–coupled seven-transmembrane receptor (ODR-10) is the first olfactory receptor whose ligand was elucidated. Using chemotaxis and thermotaxis as behavioral paradigms, neural plasticity incl...

Lentivirus Replication and Regulation

Abstract: ▪ Abstract Lentiviruses are associated with chronic diseases of the hematological and neurological systems in animals and man. In particular, human immunodeficiency virus type 1 (HIV-1) is the etiological agent of the global AIDS epidemic. The genomes of lentiviruses are complex, encoding a number of regulatory and accessory proteins not found in other retroviruses. This complexity is reflected in their replication cycle, which reveals intricate regulatory pathways and unique mechanisms for viral persistence. In this review, we highlight some of these unique features for HIV-1, with particular focus on the transcriptional and posttranscriptional control of gene expression. Although our understanding of the biology of HIV-1 is far from complete, the knowledge gained thus far has already led to novel strategies for both virus intervention and exploiting the lentiviruses for therapeutic applications.

Shufflons: Multiple Inversion Systems and Integrons

Abstract: Conservative site-specific recombination functions to create biological diversity in prokaryotes Simple site-specific recombination systems consist of two recombination sites and a recombinase gene The plasmid R64 shufflon contains seven recombination sites, which flank and separate four DNA segments Site-specific recombinations mediated by the product of the rci gene between any two inverted recombination sites result in the inversion of four DNA segments independently or in groups The shufflon functions as a biological switch to select one of seven C-terminal segments of the PilV proteins, which is a minor component of R64 thin pilus The shufflon determines the recipient specificity in liquid matings of plasmid R64 Other multiple inversion systems as well as integrons, which are multiple insertion systems, are also described in this review

Toward an integrated genetic epidemiology of parasitic protozoa and other pathogens.

Abstract: ▪ Abstract Due to the increase of human migrations, the appearance of emerging and reemerging endemies, growing antibiotic resistance, and climatic changes, infectious diseases most probably constitute the major challenge for medicine in the next century. The advent of molecular methods of pathogen characterization has considerably improved our knowledge of the epidemiology of these diseases. However, the use of concepts of evolutionary genetics for interpreting “molecular epidemiology” data remains limited, although the application of such methods would broaden considerably the scope of this field of research, and allow epidemiologic and taxonomic approaches to be ascertained on a much firmer basis. In turn, pathogens, hosts, and vectors provide fascinating models for basic research. The artificial character of the border between “basic” and “applied” research is especially apparent with regard to the “integrated genetic epidemiology of infectious diseases” concept. The goal of this chapter is to evaluat...

History of Plant Population Genetics

Abstract: This review of plant population genetics focuses on the genetic foundations of the processes that have led to documentable improvements in cultivated plants since the earliest domestications took place perhaps 13,000 years ago. Nearly all human civilizations have depended heavily on inbreeding plants (particularly wheat, barley, soybeans and other inbreeding legumes), as well as outbreeding vegetatively propagated species (white potatoes, yams) as their dietary standbys. The principal exception is maize (corn), an annual seed-produced outbreeder in nature. It is noteworthy that maize joined wheat, rice, and barley as a truly major crop worldwide only after its conversion to self-pollination combined with hybridization between favorably interacting inbred lines increased yield of maize several-fold in the twentieth century.

Family values in the age of genomics: comparative analyses of temperate bacteriophage HK022.

Abstract: ▪ Abstract HK022 is a temperate coliphage related to phage λ. Its chromosome has been completely sequenced, and several aspects of its life cycle have been intensively studied. In the overall arrangement, expression, and function of most of its genes, HK022 broadly resembles λ and other members of the λ family. Upon closer view, significant differences emerge. The differences reveal alternative strategies used by related phages to cope with similar problems and illuminate previously unknown regulatory and structural motifs. HK022 prophages protect lysogens from superinfection by producing a sequence-specific RNA binding protein that prematurely terminates nascent transcripts of infecting phage. It uses a novel RNA-based mechanism to antiterminate its own early transcription. The HK022 protein shell is strengthened by a complex pattern of covalent subunit interlinking to form a unitary structure that resembles chainmail armor. Its integrase and repressor proteins are similar to those of λ, but the differen...

The French School of Genetics: From Physiological and Population Genetics to Regulatory Molecular Genetics

Abstract: French genetics had unusual beginnings. There are clear indications that the French biological establishment resisted Mendelian genetics strenuously from about 1910 to 1940. From about 1930 to 1950 several unconventional research programs with a strongly physiological orientation paved the way for the full entrance of French biology into genetics after World War II. This review examines some salient features of this history to clarify the strengths, weaknesses, and distinctive features of French genetics until about 1965. We suggest that after that data French genetics slowly merged into the international mainstream as genetics has become a largely molecular discipline.