Clarification appended
To their surprise, UCLA scientists found that males and females
really are not as different as they thought when it comes to the
expression of genes in their brains, though they found significant
differences in other body tissues.
“Males and females think and behave differently and have
different risks for neuropsychiatric diseases, but we found that
the degree of differences in genetic expression in the brain is
much less than that of other types of tissue,” said Xia Yang,
lead author of the study and postdoctoral fellow in cardiology at
the David Geffen School of Medicine.
However, the analysis was done on the basis of the brain as a
whole and not on separate structures.
The study, published in the August issue of the journal Genome
Research, examined the expression of genes in the fat, liver,
muscle and brain tissues of mice, who share 99 percent of our
genes. Human males and females have exactly the same genetic code,
yet each gender expresses different genes.
“Males and females have the same genes but the differences
come from what genes are turned on, and on what level,” said
Dr. Arthur Arnold, chair of the department of physiological
science, who also participated in the study.
The prolactine gene, which affects maternal behavior, is
expressed three times higher in females, Yang said.
On the other hand, the PINK1 gene expression level, which plays
a role in Parkinson’s disease, is slightly higher in male
mice, Yang added.
But the question surrounds the cause of the differences in gene
expressions.
“We believe that most of the sex differences in gene
expression are secondary to hormonal effects, yet only a limited
number of these are directly controlled by sex hormones,”
said Dr. Thomas A. Drake, UCLA professor of pathology. “What
we think is happening is something of a ripple effect.”
Compared to brain tissue, where hundreds of genes showed
different expression patterns based on the gender, the study found
that the other types of bodily tissue contained thousands of
differences in gene expression.
“Thousands of genes behave differently in the same organs
of males and females ““ something never detected to this
degree,” said Drake.
“Three-quarters of the genes in the liver are expressed
differently based on the gender,” Arnold said. “Lots of
these small differences add up, creating an overall effect,”
he said.
These findings imply that male and female livers function the
same but work at different rates, Yang said.
“If one gender metabolizes a particular drug faster, it
could leave too little of the medication in the system,” she
said. “Most medication dosages for women have been based on
clinical trials that are primarily conducted on men.”
“Our ultimate goal is to link specific sexually dimorphic
genes or pathways with specific traits influenced by sex,”
said Yang.
“This is important because of their potential relevance to
the common diseases and physiological processes such as lipid
metabolism, drug response, and neurological and psychiatric
diseases,” Yang said. “Once we understand the gender
gap in disease mechanisms, we can create new strategies for
designing and testing new sex-specific drugs.”