DNA link between man and mouse
Earlier this year, researchers mapping the human genome estimated that
human DNA contains about 30,000 genes.
Now, based on the first-ever look at comparable sections of human and
mouse DNA, a team of Walnut Creek-based Joint Genome Institute (JGI) scientists
has confirmed that estimate as roughly accurate.
The team, led by Lab biomedical scientist Lisa Stubbs, details its findings
— based on comparing human chromosome 19 with similar sections of
mouse DNA — in last Friday’s edition of the journal Science.
In addition to Stubbs, the study’s analysis was performed by Paramvir
Dehal, a UC Davis graduate student, Livermore computer scientist Art Kobayashi
and a team of JGI computer scientists and biologists.
The sequencing of the mouse DNA, which was done between April and October
of last year, was led by former Joint Genome Institute Director Elbert
Branscomb, current JGI Director Trevor Hawkins and sequencing director
Paul Predki.
"There had been speculation that aligning the human and mouse DNA
sequence might reveal many more genes," Stubbs said. "However,
if chromosome 19 is indicative of other chromosomes, the estimate of 30,000
genes is fairly accurate."
Before the comparison of human and mouse DNA, researchers had thought
that human chromosome 19 had about 1,100 genes.
With the comparative analysis, about 1,200 were found, Stubbs said.
"We’ve wanted to compare human and mouse DNA to help us find
human genes and to figure out how they function," she said.
"Another reason is that researchers use mouse models for studying
diseases and testing medicines, and to do this properly, it’s important
to understand the differences and similarities between the two species."
Through their study, the JGI team found apparent additional sections of
more than 300 human genes, confirmed the existence of other computer-predicted
genes and provided evidence to discard other gene predictions, according
to Stubbs.
The team discovered "candidate" regulatory sequences for genes
throughout chromosome 19. Regulatory sequences tell individual genes when
and in which cells to activate.
In the study, the researchers found that about 90 percent of the human
genes in chromosome 19 were also located in similar sections of mouse
DNA, Stubbs said.
The approximately 10 percent of human or mouse genes that are unique to
each other are the type of genes that tend to duplicate, or make extra
copies, over time.
These genes include zinc finger genes, which produce proteins that control
the activity levels of other genes; olfactory receptor genes, which are
responsible for the sense of smell; and the genes encoding receptors for
pheromones, which serve as a chemical attractant for mating and other
social behavior.
Mouse and human DNA contain different complements of these types of genes
because active duplications have created new genes specifically in primates
or rodents.
Established in 1996, the JGI is a consortium of scientists, engineers
and support staff from three Department of Energy national laboratories
— Lawrence Berkeley, Lawrence Livermore and Los Alamos. The institute
performed the sequencing for three human chromosomes - 5, 16, and 19.
Other members of the sequencing or sequence analysis teams were: Anne
Olsen, Peg Folta, Susan Lucas, Miriam Land, Astrid Terry, Carol Ecale
Zhou, Sam Rash, Qing Zhang, Laurie Gordon, Joomyeong Kim, Christopher
Elkin, Martin Pollard, Paul Richardson, Dan Rokhsar and Ed Uberbacher.
In the future, the LLNL research team plans to try to confirm the apparent
gene extensions and test the function of the regulatory sequences, determining
how and where the genes are activated, Stubbs said.