Waterston RH et al. J Neurogenet "John Sulston (1942-2018): a personal perspective."

Waterston RH, Moerman DG

[J Neurogenet]

John Sulston changed the way we do science, not once, but three times - initially with the complete cell lineage of the nematode <i>Caenorhabditis elegans</i>, next with completion of the genome sequences of the worm and human genomes and finally with his strong and active advocacy for open data sharing. His contributions were widely recognized and in 2002 he received the Nobel Prize in Physiology and Medicine.

Waterston RH (1981) Genetics "A second informational suppressor, SUP-7 X, in Caenorhabditis elegans."

Waterston RH

[Genetics, 1981]

More than 30 independent suppressor mutations have been obtained in the nematode C. elegans through reversion analysis of two unc-13 mutants. Many of the new isolates map to the region of the previously identified informational suppressor, sup-5 III (WATERSTON and BRENNER 1978). Several of the other suppressor mutations map to the left half of the X-linkage group and define a second suppressor gene, sup-7 X. In tests against 40 mutations in six genes, the sup-7(st5) allele was found to suppress to a greater extent the same alleles acted on by sup-5(e1464). Like sup-5(e1464), sup-7(st5) acts on null alleles of the myosin heavy-chain gene unc-54 I (MACLEOD et al. 1977; MACLEOD, WATERSTON and BRENNER 1977) and the putative paramyosin gene unc-15 I (WATERSTON et al. 1977). Chemical analysis of unc-15(e1214); sup- 7(st5) animals show that paramyosin is restored to more than 30% of the wild-type level.--As was observed for sup-5(e1464), suppression by sup-7(st5) is dose dependent and is greater in animals grown at 15 degrees than at 25 degrees. However, associated with this increased suppression is a decreased viability of sup-7(st5) homozygotes. Reversion of the lethality has resulted in the isolation of deficiency mutations that complement st5 lethality, but lack suppressor function. These properties of sup-7(st5) suggest that it, like sup-5(e1464), is an information suppressor of null alleles, and its reversion via deficiencies further narrows the possible explanations of its action.

Waterston RH et al. (1974) J Mol Biol "Paramyosin of Caenorhabditis elegans."

Waterston RH, Epstein HF, Brenner S

[J Mol Biol, 1974]

Paramyosin has been isolated from the nematode, Caenorhabditis elegans. Its identity has been established by a variety of criteria, including purification, molecular weight, immunological cross reactivity with known paramyosin and formation of characteristic paracrystals. The presence of paramyosin in both pharyngeal and body-wall musculature was shown by a technique that allows analysis by sodim dodecyl sulphate gels of the protein in a single worm. The possibility of defining the role of paramyosin in the structure and function of the invertebrate muscle through the isolation of mutants in this protein is

Waterston RH et al. (1992) Nat Genet "A survey of expressed genes in Caenorhabditis elegans."

Durbin RM, Waterston RH, Huynh C, Halloran N, Shownkeen R, Green P, Hillier L, Martin C, Craxton M, Coulson AR

[Nat Genet, 1992]

As an adjunct to the genomic sequencing of Caenorhabditis elegans, we have investigated a representative cDNA library of 1,517 clones. A single sequence read has been obtained from the 5' end of each clone, allowing its characterization with respect to the public databases, and the clones are being localized on the genome map. The result is the identification of about 1,200 of the estimated 15,000 genes of C. elegans. More than 30% of the inferred protein sequences have significant similarity to existing sequences in the databases, providing a route towards in vivo analysis of known genes in the nematode. These clones also provide material for assessing the accuracy of predicted exons and splicing patterns and will lead to a more accurate estimate of the total number of genes in the organism than has hitherto been available.

Waterston RH et al. (1977) J Mol Biol "Mutants affecting paramyosin in Caenorhabditis elegans."

Brenner S, Fishpool RM, Waterston RH

[J Mol Biol, 1977]

Four mutants of Caenorhabditis elegans with abnormal muscle structure are described which are alleles of a single locus unc-15. In one of the mutants, E1214, paramyosin is completely absent from both body-wall and pharyngeal musculature. In the other three mutants paramyosin is present but does not assemble into thick filaments. Instead paramyosin paracrystals are formed in the body-wall muscle cells. Myosin filaments lacking paramyosin cores are present in all four mutants, but these filaments fail to integrate stably into the myofilament lattice. One mutant is temperature-sensitive; all four are semi-dominant in their effect on muscle structure. The hypothesis that unc-15 is the structural gene for paramyosin is discussed.

Waterston RH et al. (1980) Dev Biol "Mutants with altered muscle structure of Caenorhabditis elegans."

Thomson JN, Waterston RH, Brenner S

[Dev Biol, 1980]

In the small nematode, Caenorhabditis elegans, mutants with disorganized myofilament lattice structure have been identified by polarized light microscopy. Genetic analysis places the mutations in 12 complementation groups which are distributed over the six linkage groups of C. elegans. The phenotypes are described for the mutants from the 9 complementation groups not previously reported on in detail. Most are paralyzed, but some exhibit essentially normal movement; mutants of two loci show changes only in later larval stages and adulthood. Morphological studies show that, in general, all the members of a complementation group show similar changes in muscle structure and that these changes are distinctive for that group. In mutants of several genes, disorganization of the myofilament lattice is general with no one component of the lattice more obviously altered than the others. In mutants of other genes specific structures are prominently altered. In one of the instances where thick filaments appear to be abnormal, double mutants combining mutations in this gene (unc-82 IV) with mutations in the gene for a myosin heavy chain or paramyosin were used to show that the unc-82 gene product probably affects thick filament assembly through its actions on paramyosin. Some possible implications of the morphological features of the mutants as well as the conclusions derived from the genetic studies are discussed.

Waterston RH et al. (1995) Proc Natl Acad Sci U S A "The genome of Caenorhabditis elegans."

Waterston RH, Sulston JE

[Proc Natl Acad Sci U S A, 1995]

The physical map of the 100-Mb Caenorhabditis elegans genome consists of 17,500 cosmids and 3500 yeast artificial chromosomes (YACs). A total of 22.5 Mb has been sequenced, with the remainder expected by 1998. A further 15.5 Mb of unfinished sequence is freely available online: because the areas sequenced so far are relatively gene rich, about half the 13,000 genes can now be scanned. More than a quarter of the genes are represented by expressed sequence tags (ESTs), All information pertaining to the genome is publicly available in the ACeDB data base.

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

Waterston RH, Brenner S

[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.

Waterston RH (1989) EMBO J "The minor myosin heavy chain, mhcA, of Caenorhabditis elegans is necessary for the initiation of thick filament assembly."

Waterston RH

[EMBO J, 1989]

Caenorhabditis elegans body wall muscle has two distinct myosin heavy chain isoforms, mhcA and mhcB. Mutations eliminating the major isoform, mhcB, have previously been shown to yield paralyzed, viable animals. In this paper we show that the minor isoform, mhcA, is essential for viability. We have utilized the known physical map position of the gene encoding mhcA to obtain two recessive lethal mutations that virtually eliminate accumulation of mhcA. The mutations are allelic, and the interactions of these alleles with mutations affecting other thick filament components are consistent with the hypothesis that the new mutations lie in the structural gene for mhcA. The homozygous mutant animals move very little and morphological analysis shows that thick filament assembly is severely impaired. Together with the location of mhcA in the center of the thick filament (Miller et al., 1983), the results suggest that mhcA has a unique role in initiating filament assembly. The homozygous mutations have an unexpected effect on morphogenesis that indicates an interaction between the muscle cells and the hypodermis during development. The resultant phenotype may be useful in the search for additional essential muscle genes.

Waterston RH et al. (1982) J Mol Biol "Genetic fine structure analysis of the myosin heavy chain gene unc-54 of Caenorhabditis elegans."

Moerman DG, Smith KC, Waterston RH

[J Mol Biol, 1982]

Taking advantage of the relative ease of detecting single wild-type animals among large numbers of Unc-54 mutant animals, rare intragenic recombinants were recovered between mutations of unc-54 I, the gene coding for the myosin heavy chain of Caenorhabditis elegans body wall musculature. Appropriate closely linked marker mutations were used to improve screening efficiency, to distinguish recombination and conversion events, and to establish the relative order of unc-54 mutations in the gene. From the analysis of more than 400 exceptional chromosomes recovered from tests involving 91 heteroallelic strains, 27 unc-54 mutations have been separated into ten distinct sites. Null mutations, comprising the majority of the mutations studied, are scattered throughout the map with the e1300 and st60 mutations located at the left and right ends, respectively. Three small deficiencies are clustered at an internal site nearer the left end. Two missense mutations lie to the right of these deficiencies. By correlating these results with molecular investigations of specific mutations, we conclude that the 5' end of the coding sequence is at the right end of the gene and is located distally on the chromosome. These correlations also demonstrate that the map includes at least 80% of the structural sequence. The genetic map allows us to infer the approximate location of mutations in the coding sequence, and should aid in the genetic dissection of