First Genetic Map of an Animal Reported Summary

  • Last updated on November 10, 2022

During the mid-1990’s, the genome sequences of a number of free-living organisms, primarily bacteria, had been published, but the genome sequence of the nematode Caenorhabditis elegans, published in 1998, represented the first for a multicellular organism.

Summary of Event

Caenorhabditis elegans (C. elegans), a millimeter-length nematode, has for several decades been the model system for study of cell differentiation in multicellular eukaryotic organisms. The organism’s rise to “prominence” began in the 1960’s, when geneticist Sydney Brenner Brenner, Sydney chose the organism for his studies in neural development. C. elegans was ideal for a number of reasons. It was a simple organism with a relatively small number of cells: 1,031 in the adult male and 959 in the adult hermaphrodite form; approximately 300 cells are neurons. The organism was easy to grow and maintain in the laboratory, and its transparent appearance allowed for study of cell differentiation following fertilization. Genetic mapping Caenorhabditis elegans [kw]First Genetic Map of an Animal Reported (Dec. 10, 1998) [kw]Genetic Map of an Animal Reported, First (Dec. 10, 1998) [kw]Animal Reported, First Genetic Map of an (Dec. 10, 1998) Genetic mapping Caenorhabditis elegans [g]North America;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] [g]Europe;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] [g]United States;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] [g]United Kingdom;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] [g]England;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] [c]Genetics;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] [c]Biology;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] [c]Science and technology;Dec. 10, 1998: First Genetic Map of an Animal Reported[10250] Sulston, John Waterston, Robert

Brenner’s contribution centered primarily on understanding the development of neural connections in the animal, a process directly analogous to that which takes place in more advanced and evolved organisms. The developmental history for each of the roughly one thousand cells was mapped during decades of study by Brenner, his students, and his coworkers. In addition to contributing to an understanding of neural development, the studies produced information related to programmed cell death and regulation of expression of genes during growth and development. Five Nobel Prizes in Physiology or Medicine Nobel Prize in Physiology or Medicine;Sydney Brenner[Brenner] Nobel Prize in Physiology or Medicine;John Sulston[Sulston] resulted from this work, with awards to Brenner, H. Robert Horvitz, and John Sulston in 2002, and to Andrew Z. Fire and Craig Mello in 2006.

Robert Waterston was originally trained in engineering, but he switched fields into biology after enrolling in such courses while spending a year in Germany. Following a meeting in 1969 with Sydney Brenner, Waterston joined Brenner’s team in Cambridge, England, and entered into a study of muscle development during differentiation in the nematode. The work continued after Waterston took a position as assistant professor of anatomy and neurobiology at Washington University in St. Louis, Missouri. During a sabbatical visit to Cambridge in the 1980’s, Waterston met John Sulston, and the two began the collaboration that resulted in sequencing of the C. elegans genome.

In 1989, the National Institutes of Health in the United States and the Medical Research Council in the United Kingdom began to fund research in the program, providing grants to both Sulston and Waterston for their work in the field. Sulston had earned his doctorate in the field of chemistry at the University of Cambridge, primarily studying synthesis of ribonucleic acid (RNA) sequences. Sulston joined Brenner’s laboratory in 1969, following a postdoctoral post at the Salk Institute. His work with Brenner consisted primarily of mapping the differentiation of cells during development, using mutations as a means of studying the roles of specific genes in the process. A pilot study produced a three-million-base sequence by 1990, resulting in full funding of the work.

After more than twenty years of work in this area, the Wellcome Trust hired Sulston in 1993 to head a large team of scientists at the Sanger Centre (now the Sanger Institute) in Cambridge, with a goal of sequencing the genomes of eukaryotic organisms in conjunction with the Human Genome Project. Human Genome Project The collaboration between Sulston’s and Waterston’s teams, which began in earnest by 1993, resulted in the 1998 publication of the first genome sequence of a multicellular organism.

What the researchers has accomplished was no easy task, as the deoxyribonucleic acid (DNA) DNA;genetic mapping sequence of the genome contained some ninety-seven million bases divided among six chromosomes. The physical map with which the teams began their sequencing work “in earnest” consisted primarily of the data from random clones. The precise order of some of these gene clones was still unclear. The two teams approached the project by cutting the DNA into relatively small fragments, then using newly evolving sequencing technology to determine the order of bases within the fragments. This process is sometimes referred to as a shotgun approach, as it involves the cutting of the DNA into fragments determined by the specific recognition of DNA sequences found in the DNA. The order of the fragments is not always immediately apparent. Hybridization and other overlapping techniques can then be applied for actual determination of the order of such fragments.

H. Robert Horvitz points to an a image of the nematode Caenorhabditis elegans. Working with this organism, he, Sydney Brenner, and John Sulston won the 2002 Nobel Prize in Physiology or Medicine for discovering genes regulating organ development and leading to apoptosis (programmed cell death)—discoveries with significant implications for cancer therapies.

(AP/Wide World Photos)

A series of overlapping clones primarily from the centers of the chromosomes were addressed first. Application of cloning using yeast artificial chromosomes Yeast artificial chromosomes (YACs) and subclones provided a means to fill in gaps and bridges among the clones.

The final sequence revealed a number of surprises. Whereas scientists initially expected to identify no more than six to seven thousand genes, similar to the number found in yeast, the actual number proved to be greater than nineteen thousand. More than 40 percent of this information had identity with genes in other eukaryotic organisms, providing additional evidence for a common evolutionary history. In particular, the conserved similarity between yeast (and other fungi) and C. elegans, separated by nearly one billion years of evolutionary change, was a surprise. Nearly 20 percent of the genetic information in the nematode was shown to be nearly identical to about half the seven thousand genes found in the single-celled yeast, suggesting an important role for such genes in survival of the respective organisms.

In part, the similarity of so many genes allowed for an increased understanding of what it means to be a eukaryote. For example, sequencing confirmed what had already been suspected, that evolution of an organism may occur both through the acquisition of new genetic material and through the shifting of pieces of genes from one site to another. Some of these shifts are the result of transposons, sequences of bases that can move, or transpose, from one site to another. At least some of these sequences, or domains, function in regulation of gene expression. The similarity of such domains found in many different genes supports the view that transposition may account for the presence of such sequences.

Significance

Determination of the genome sequences of organisms represented an important step in humankind’s understanding of the regulation and molecular biology of increasingly complicated forms of life. Among these discoveries has been the revelation that the size of the genome does not necessarily represent the complexity of the organism or the number of active genes. The human genome, for example, was found to be smaller than that from less evolved forms of life while containing roughly the same number of genes as those in other multicellular organisms.

Previous sequencing had utilized the genomes from prokaryotic organisms such as bacteria and viruses; the sole eukaryotic genome that had been sequenced was that of the single-celled yeast. The published sequence of the C. elegans genome was merely the first from numerous multicellular organisms, culminating with the first report in 2000 of that for the human genome. Surprisingly, the number of genes is similar in both: approximately twenty to twenty-five thousand for each. Because C. elegans is “merely” a nematode, no ethical questions arise concerning the creation of directed mutations as a means of understanding the steps involved in biological processes. As a multicellular organism, C. elegans lends itself to the study of cellular differentiation, regulation, and reproduction, much of which is analogous to what takes place during human development.

Previous attempts at genome sequencing involved relatively smaller, single-celled organisms; thus the work with C. elegans represented the first attempt to apply such techniques on a larger scale. The researchers’ success lent impetus to further applications with more evolved organisms. Genetic mapping Caenorhabditis elegans

Further Reading
  • citation-type="booksimple"

    xlink:type="simple">Allison, Lizabeth A. Fundamental Molecular Biology. Malden, Mass.: Blackwell, 2007. College-level text is aimed at readers with a basic knowledge of biology. Discusses techniques used in sequencing and provides a summary of the major organisms for which the genomes have been sequenced.
  • citation-type="booksimple"

    xlink:type="simple">Brown, Andrew. In the Beginning Was the Worm: Finding the Secrets of Life in a Tiny Hermaphrodite. New York: Columbia University Press, 2003. Describes the history of the use of C. elegans as a laboratory tool. Includes explanations of how an understanding of genome regulation in the organism is applied in other systems.
  • citation-type="booksimple"

    xlink:type="simple">“C. elegans Sequencing Consortium.” Science 282 (December 11, 1998): 2012-2019. Technical report by the two teams that sequenced the genome. Includes discussion of the significance of the completed work.
  • citation-type="booksimple"

    xlink:type="simple">Epstein, Henry F., and Diane C. Shakes, eds. Caenorhabditis elegans: Modern Biological Analysis of an Organism. San Diego, Calif.: Academic Press, 1995. Laboratory handbook describes techniques and applications of this “workhorse” organism in the study of regulation among multicellular eukaryotes.
  • citation-type="booksimple"

    xlink:type="simple">Lodge, Julia, Pete Lund, and Steve Minchen. Gene Cloning: Principles and Applications. New York: Taylor & Francis, 2007. Summarizes the techniques used in cloning and the sequencing of genetic information. Includes discussion of the role of C. elegans in such research.
  • citation-type="booksimple"

    xlink:type="simple">Moore, Janet. An Introduction to the Invertebrates. 2d ed. New York: Cambridge University Press, 2006. Discusses the evolutionary development of organisms and the relationship of C. elegans in the phylogenetic scheme. Addresses the roles of specific genes in regulation.

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