Gene study links males of three species

by Emily Dalnodar

Male humans, fruit flies and worms have something in common.
No, not that.
According to a recent report from University biologists, all three share a common gene that makes them male.
A three-year collaborative study headed by University researcher and molecular biologist David Zarkower discovered that not only do the three species share a common gene, but that gender is something that evolution determined thousands of years ago and maintains even today.
And the group says this research might be able to one day tell people affected by deformed genes why it happened.
The initial work that led to the University study came from England 12 years ago. Jonathan Hodgkin, who collaborated with Zarkower, found a nematode, a common roundworm, that had a sexual deformity. It was missing its sex bristles, which help it locate a mate.
Hodgkin located the approximate area of where the gene should be, but he did not isolate the gene itself.
A few years later, Ken Burtis, a researcher at Stanford University, discovered a gene in fruit flies, called the doublesex gene that manipulates the gender of that species.
But it wasn’t until Zarkower and his team of researchers’ work that any correlations between worms and flies were found.
The research was funded by grants from the National Institutes of Health, the Minnesota Medical Foundation and the University Medical School. The research results appeared in Thursday’s edition of Nature magazine.
The project team also includes: Chris Raymond, a graduate student in biochemistry, Emily Parker, a lab technician and junior scientist in the Institute of Human Genetics, and Woelsung Yi, a graduate student in biochemistry.
The team isolated the gene that Hodgkin had suspected of causing the sexual deformities in the roundworm.
To do this, the research team first cloned a worm found to have a deformity, which they suspected the defective gene caused.
All the members of the research team gave their input and suggestions and were a big part of the process, Raymond said.
After a worm with the deformed gene is cloned, researchers mash it up with other worms into a paste-like substance and then purify it with a solution so that only the DNA is left. Purifiers are usually enzymes or phenol that strip away the proteins leaving only the DNA.
“We don’t use the same procedure with the humans, though,” Zarkower said.
After isolating the gene, called mab-3, Zarkower saw that it looked a lot like the doublesex gene in fruit flies.
“I thought, if this gene exists in flies and worms, why not humans?” Zarkower said.
The team of researchers found the human counterpart to the doublesex and mab-3 gene, called DMT1 by using a computer database that keeps track of all human DNA. After finding a match, the next step was to find the chromosome on which the gene resided.
The Clinical Cytogenics Lab in the Mayo Clinic collaborated in the efforts by mapping out where, in human DNA, the DMT1 gene lies.
“We know that every gene eventually has a particular place and we had to find out which one DMT1 is found on,” said Betsy Hirsch, associate professor in the department of laboratory medicine and pathology.
Humans have 23 pairs of chromosomes, which are numbered.
“Like Alzheimer’s disease is found on chromosome 21, DMT1 is found on a particular chromosome,” Hirsch said. “It is at the very tip of the ‘short arm’ of chromosome 9.”
She also said this was an interesting discovery because there had been several children born with improper sexual development that also had problems with their chromosome 9.
And although it is not clear exactly what the gene does, researchers know that the gene definitely has an effect on the gender of human species.
“A Y chromosome is essential for a male, but not the only thing,” Zarkower said.
People who have an X and a Y chromosome are normally born male, but if that person is missing one of the two normal copies of the DMT1 gene, that person will have serious sexual complications.
Some people with this condition, which is extremely rare, are born female but will be sterile. Some will be born hermaphrodites, having both the male and female organs, and some will be born without being able to determine what gender they are, Zarkower said.
Now, the researchers are looking exclusively at women who have XY chromosomes and are missing one of the DMT1 genes. They are looking for a mutation in the gene to make sure that the gene does, indeed, determine sex.
“In terms of helping people immediately, it’s not clear. (The mutation) happens in the embryo so early, there’s nothing you can do about it,” Zarkower said.
He said that maybe in the future doctors will be able to take a cell out of the womb before it starts to develop and determine any problems before they start, but this is just the initial research.