Worm, Yeast Genes Provide Clues About Human Gene Functions
STANFORD, Calif.--(BW HealthWire)--Dec. 11, 1998--For the first time, scientists have compared the entire genomes of two primitive organisms in the same evolutionary pathway that leads to plants and animals. The comparison lends strong support to assumptions that the genes of ''model organisms'' such as yeast, worm and fruit fly will reliably predict the function of newly discovered human genes.
''This study represents an important advance,'' said David Botstein, PhD, Stanford W. Ascherman professor of genetics at Stanford University School of Medicine and senior author of the study. ''It shows that we can learn the function of worm genes from the yeast, and vice versa, which makes it likely that we can also learn the function of conserved human genes from either of these organisms.''
The study, conducted by Stanford's Botstein, J. Michael Cherry, PhD, and colleagues, in collaboration with scientists at Boston University and the National Institutes of Health, was reported in the December 11 Science in a special section devoted to the release of the genetic sequence of the nematode worm.
The findings show that most of the core biological functions in the unicellular yeast, commonly known as baker's yeast, and the multicellular nematode worm are performed by proteins similar in sequence and number, indicating that protein functions identified in one species can be assigned to the other. Linking similar gene sequences and protein functions in organisms as disparate as yeast and worm paves the way for similar comparisons in all eukaryotic organisms -- from yeast to worms, fruit flies, mice and humans, the researchers said.
The scientists compared the 6,217 yeast genes with the 19,099 genes of the nematode worm. They found that 40 percent of the yeast and 20 percent of the worm sequences code for highly conserved proteins that carry out biological processes common to both microorganisms -- such as DNA and RNA metabolism and protein folding, trafficking and degradation. These proteins show one-to-one relationships, suggesting that the genes encoding them were present and their functions were already established in the common ancestor of fungi and animals.
Specialized processes unique to the worm use novel proteins characteristic of multicellular plants and animals. It is largely these specialized genes that triple the size of the worm genome over that of the yeast.
The researchers point out that biochemical and biological experiments must still be conducted to unequivocally prove the proteins' functions, but the sequence analyses will enable such experiments to be designed with greater specificity. Duplication of effort arising from sequencing conserved genes in closely related species may also be avoided.
The nematode worm, Caenorhabditis elegans, is only the second eukaryote for which the genome has been completely sequenced. The sequence of the first eukaryote, the yeast Saccharomyces cerevisiae was completed in 1996 by an international team that included Stanford scientists. Several bacteria (prokaryotes) have also been sequenced.
Further functional analysis of the yeast genome is reported in the December issue of Molecular Biology of the Cell. Patrick Brown, MD, PhD, a Howard Hughes Medical Institute investigator in Stanford's department of Biochemistry, members of Botstein's group and collaborators at Cold Spring Harbor describe 800 yeast genes involved in the cycle of cell division.
These genes are involved in processes that enable each cell to duplicate its genetic material and split into two progeny cells. Such genes in humans are being actively explored as possible targets for new anti-cancer drugs.
This work was supported by grants from the National Institutes of Health. The Saccharomyces Genome Database, administered by J. Michael Cherry and David Botstein, is supported by a grant from the National Human Genome Research Institute.
Contact:
Stanford University Medical Center
Kristin Weidenbach, 650/723-0272 or 723-6911
www-med.stanford.edu |
