Brenner S (2009) Genetics "In the beginning was the worm ..."

Brenner S

[Genetics, 2009]

Brenner S (1974) Genetics "The genetics of Caenorhabditis elegans."

Brenner S

[Genetics, 1974]

Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggest that, just as in Drosophila, the genetic units in C. elegans are large.

Brenner S et al. (1993) Nature "Characterization of the pufferfish (Fugu) genome as a compact model vertebrate genome."

Elgar G, Brenner S, Sandford R, Aparicio S, Venkatesh B, Macrae A

[Nature, 1993]

Cloning and sequencing techniques now allow us to characterize genes directly instead of having to deduce their properties from their effects. This new genetics reaches its apotheosis in the plan to obtain the complete DNA sequence of the human genome, but this is far beyond the capacity of present sequencing methods. Small 'model' genomes, 'such as those of Escherichia coli (4.7 megabases (Mb) and yeast (14 Mb), or even those of Caenorhabditis elegans (100 Mb) and Drosophila (165 Mb), are better scaled to existing technology. The yeast genome will contain genes with functions common to all eukaryotic cells, and those of simple multicellular organisms may throw light on the genetic specification of more complex functions. However, vertebrates differ in their morphology and development, so the ideal model would be a vertebrate genome of minimum size and complexity but with maximum homology to the human genome. Here we report the characterization of the small genome (400 Mb) of the tetraodontoid fish, Fugu rubripes. A random sequencing approach supported by gene probing shows that the haploid genome contains 400 Mb of DNA, of which more that 90% is unique. This genome is 7.5 times smaller than the human genome and because it has a similar gene repertoire it is the best model genome for the discovery of human genes.

Strange K (2006) Methods Mol Biol "An overview of C. elegans biology."

Strange K

[Methods Mol Biol, 2006]

The establishment of Caenorhabditis elegans as a "model organism" began with the efforts of Sydney Brenner in the early 1960s. Brenner''s focus was to find a suitable animal model in which the tools of genetic analysis could be used to define molecular mechanisms of development and nervous system function. C. elegans provides numerous experimental advantages for such studies. These advantages include a short life cycle, production of large numbers of offspring, easy and inexpensive laboratory culture, forward and reverse genetic tractability, and a relatively simple anatomy. This chapter will provide a brief overview of C. elegans biology.

Sulston JE et al. (1974) Genetics "The DNA of Caenorhabditis elegans."

Sulston JE, Brenner S

[Genetics, 1974]

Chemical analysis and a study of renaturation kinetics show that the nematode, Caenorhabditis elegans, has a haploid DNA content of 8 X 10(7) base pairs (20 times the genome of E. coli). Eighty-three percent of the DNA sequences are unique. The mean base composition is 36% GC; a small component, containing the rRNA cistrons, has a base composition of 51% GC. The haploid genome contains about 300 genes for 4S RNA, 110 for 5S RNA, and 55 for (18 + 28)S RNA.

Karn J et al. (1983) Proc Natl Acad Sci U S A "Protein structural domains in the Caenorhabditis elegans unc-54 myosin heavy chain gene are not separated by introns."

Barnett L, Brenner S, Karn J

[Proc Natl Acad Sci U S A, 1983]

The 1,966-amino acid unc-54 myosin heavy chain sequence was determined from DNA sequence studies of the cloned gene. The gene is split by eight short introns, 48-561 base pairs long, and appears to lack a "TATA" box at its promoter. The physical map of the gene was aligned with the genetic map by locating two point mutations and three internal deletions: 0.01 map units correspond to approximately 5 kilobases. Comparison of the unc-54 protein sequence with the sequence of a second myosin heavy chain from nematode, indicates that the globular head sequence S-1 is more highly conserved than the alpha-helical coiled-coil rod. Major sites of proteolysis in S-1 are associated with variable sequences that have the characteristics of surface loops. In both genes there is no correlation between the positions of introns and the major protein structural

Hodgkin JA et al. (1977) Genetics "Mutations causing transformation of sexual phenotype in the nematode Caenorhabditis elegans."

Hodgkin JA, Brenner S

[Genetics, 1977]

Ten mutations are described that transform genotypic hermaphrodites of the nematode Caenorhabditis elegans into phenotypic males. These fall into three autosomal complementation groups, termed tra-1, tra-2, and tra-3. Two alleles of tra-1 produce almost complete transformation, to a fertile male phenotype; such transformed animals are useful for analyzing sex-linked genes. All alleles of tra-1 and tra-2 are recessive; the one known allele of tra-3 is both recessive and maternal in effect. Where tested, both XX and XXX hermaphrodites are transformed into males, but XO males (true males) are unaffected by these mutations. It is suggested that these genes are actually involved in hermaphrodite development and have no role in male development.

Maruyama IN et al. (1991) Proc Natl Acad Sci U S A "A phorbol ester/diacylglycerol-binding protein encoded by the unc-13 gene of Caenorhabditis elegans."

Brenner S, Maruyama IN

[Proc Natl Acad Sci U S A, 1991]

Mutations in the unc-13 gene cause diverse defects in the nervous system of the nematode Caenorhabditis elegans. Molecular cloning of the gene and sequencing of the cDNA revealed that the product encodes a protein, 1734 amino acids in length, with a central domain with sequence similarity to the regulatory region of protein kinase C. The domain was expressed in Escherichia coli and shown to bind specifically to a phorbol ester in the presence of calcium; diacylglycerol inhibited the binding in a competitive manner. These findings confirm that the unc-13 gene product has binding sites similar to those of protein kinase C and may be a component of an alternative transduction pathway of the diacylglycerol signal to a different effector function in the nervous system.

Waterston RH et al. (1978) Nature "A suppressor mutation in the nematode acting on specific alleles of many genes."

Brenner S, Waterston RH

[Nature, 1978]

A suppressor mutation has been isolated in Caenorhabditis elegans through reversion analysis of a muscle-defective mutant. The suppressor mutation acts on specific alleles of at least six genes and in one case we have been able to show that it partially restores functional gene product to a mutant otherwise lacking that product. These and other features of the suppressor suggest that it acts at some step in information transfer, perhaps through mechanisms similar to those described previously in microorganisms.

Anderson P et al. (1984) Proc Natl Acad Sci U S A "A selection for myosin heavy chain mutants in the nematode Caenorhabditis elegans."

Anderson P, Brenner S

[Proc Natl Acad Sci U S A, 1984]

The unc-54 gene of Caenorhabditis elegans encodes an abundant myosin heavy chain protein expressed in body-wall muscle cells. We have designed genetic techniques that select directly for unc-54 mutants. This selection is based upon properties of the unc-54 dominant allele e1152. Mutations that eliminate dominance of e1152 are null alleles of unc-54. Deletions have been identified by their genetic properties. We have defined mutationally a number of essential genes near unc-54, and we have described the genetic fine structure of this region of linkage group I. As much as 27% of the unc-54 mutations induced by the bifunctional alkylating agent 1,2,7,8-diepoxyoctane are multisite deletions. Extrachromosomal free duplications that include unc-54 are also described.