Most of the science looking at gender differences among mammals have focused on physiological differences, but new research suggests many of those more outward-facing differences — like height and facial hair — are rooted in differences in the way males and females express their genes.

A new survey of mammalian RNA revealed genome-wide variations in gene expression between male and female mammals. The research — published this week in the journal Science — could explain differences in disease risk for males and females. Men are more likely to experience heart disease, for example, while women are more likely to be diagnosed with autoimmune disease.

Researchers determined that sex-biased gene expression accounts for 12 percent of the difference in average height between males and females.

"Discovering contributions of sex biased gene expression to height is exciting because identifying the determinants of height is a classic, century-old problem, and yet by looking at sex differences in this new way we were able to provide new insights," David Page, director of the Whitehead Institute at MIT, said in a news release. "My hope is that we and other researchers can repeat this model to similarly gain new insights into diseases that show sex bias."

If a gene is sex-biased, the same gene can be inherited by a son and daughter, but could be expressed differently in each child. The sex-biased genes identified in humans were not always the same genes found to be sex-biased in different animal species. The discovery has implications for medical research that relies on animal models to study human diseases.

Scientists did identify some genes that appear to have evolved the sex bias in an early mammalian ancestor and maintained that bias across millions of years of evolution. But the majority of sex-biased genes became so only recently and are unique to a single species or lineage, like rodents or primates.

"We're not saying to avoid animal models in sex differences research, only not to take for granted that the sex biased gene expression behind a trait or disease observed in an animal will be the same as that in humans," said Sahin Naqvi, former MIT graduate student, now a postdoctoral researcher at Stanford. "Now that researchers have species and tissue-specific data available to them, we hope they will use it to inform their interpretation of results from animal models."

Researchers are now working to understand the biochemical mechanisms that enable sex-biased gene expression. Early tests suggests sex-biased transcription factors play an important role in controlling the expression of sex-biased genes.

"We're beginning to build the infrastructure for a systematic understanding of sex biases throughout the body," Page said. "We hope these data sets are used for further research, and we hope this work gives people a greater appreciation of the need for, and value of, research into the molecular differences in male and female biology."

Experiments reveal how DNA methylation affects gene expression in humans
Washington (UPI) Jul 19, 2019 –

New research suggests DNA methylation and transposons can help explain the genetic origins of serious human diseases.

Transposons, DNA sequences that resemble ancient viral fragments, make up more than half of the human genome. Most of the time, these sequences are turned off. They're kept silent by a mechanism called DNA methylation.

Researchers suggest that when transposons are activated, they can trigger the development of serious human diseases.

Now, for the first time, scientists have managed to turn off DNA methylation in human stem cells.

Transposons are sometimes called jumping genes, as they can integrate themselves into DNA sequences, triggering genetic changes that can lead to harmful physiological changes. During fetal development, DNA methylation prevents transposons from interfering with normal gene expression.

"Sometimes, however, DNA methylation is disrupted and studies have shown that this is significant in certain cancer tumors and in some neuropsychiatric diseases," Johan Jakobsson, professor at Lund University in Sweden, said in a news release. "DNA methylation is used as a target for therapy in certain cancer types, such as leukemia, but we still lack knowledge about why this is effective and why it only works for certain types of cancer."

In the lab, Jakobsson and his colleagues used the gene-editing technology known as CRISPR/Cas9 to prevent DNA methylation in human stem cells. Scientists shared the results of their experiments this week in the journal Nature Communications.

"The results were very surprising. If you shut down DNA methylation in mouse cells, they don't survive," Jakobsson said. "But when DNA methylation was shut down in the human nerve stem cells, they survived and a specific set of transposons were activated. These transposons in turn affected many genes that are important in the development of the nerve cells."

In follow up studies, researchers hope to turn DNA methylation off and on in cancer cells like glioblastoma.