All Things Being (Un)Equal: Scientists Discover Gene that Breaks Traditional Laws of Inheritance

One of the most fundamental laws of biology is about to be turned on its head, according to new research from scientists at the University of North Carolina (UNC) School of Medicine.

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As reported in the journal PLOS Genetics, UNC researchers identified a gene that does not obey traditional laws that determine how genes get passed down from parents to offspring. In experiments on laboratory mice, they found a gene called R2d2 causes female mice to pass on more genetic information than the males did—an observation that appears to contradict principles of genetic inheritance set forth more than a century ago.

As you may (or may not) remember from freshmen biology class, the laws of inheritance were laid down by the 19th century monk Gregor Mendel. Through meticulous observations of his garden’s pea plants, he found that each parent contributes their genetic information equally to their offspring.

But 150 years of scientific discovery later, scientists have discovered that this isn’t always the case.

Instead, in some cases one of the parents will contribute a greater percentage of genetic information than the other, a process called meiotic drive. Scientists had seen evidence of this process occurring in mammals for quite some time, but hadn’t narrowed down the driver of the process to a particular gene. According to UNC researchers, R2d2 is that gene. Senior author Fernando Pardo-Manuel de Villena explains:

“R2d2 is a good example of a poorly understood phenomenon known as female meiotic drive—when an egg is produced and a ‘selfish gene’ is segregated to the egg more than half the time.”

Pardo-Manuel de Villena notes that one example of this process occurs during trisomies—when three chromosomes (two from one parent and one from the other) are passed down to the embryo. The most common trisomy, trisomy 21, is more commonly known as Down Syndrome.

With these findings, Pardo-Manuel de Villena and the team are hoping to gain important insights into the underlying cause of trisomies, as well as the underlying causes for miscarriage—which are often not known.

“Understanding how meiotic drive works may shed light on the … abnormalities underlying these disorders,” said Pardo-Manuel de Villena.

This research was performed in large part by first author John Didion, who first discovered R2d2 when breeding two different types of mice for genetic analysis. Using whole-genome sequencing of thousands of laboratory mice, Didion and his colleagues saw that genes were passed down equally from each mouse’s parents. But a small section, smack dab in the middle of chromosome 2, was different.

Further analysis revealed that this section of chromosome 2 had a disproportionately larger number of genes from the mouse’s mother, compared to its father—showing a clear example of female meiotic drive. And at the heart of it all, Didion discovered, was the R2d2 gene.

The UNC team are already busy diving deeper into the relationship between R2d2 and meiotic drive with a focus on understanding, and one day perhaps correcting, genetic abnormalities in the developing embryo.

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