What is Mitochondrial Inheritance

Mitochondrial DNA: also from the father?

Contradiction to the current theory: Contrary to previous assumptions, mitochondrial DNA cannot only be passed on from the mother to the offspring. Instead, this genetic material from the cell's power plants is apparently also inherited from the father in some cases. Researchers have found evidence of this in several people from three unrelated families. Their discovery calls into question a dogma of heredity that has been valid for a long time.

The largest part of our genome lies in the cell nucleus and is passed on from both parents to children. In addition to this chromosomal DNA, however, we have other genetic material at our disposal: It is in the cells' power stations, the mitochondria. Since sperm usually only transfer their cell nucleus during fertilization, the mitochondrial DNA of every person comes from the mother's egg cell. The genetic material in the mitochondria is therefore inherited exclusively from the mother - at least that's what people thought until now.

Mitochondria in view

Scientists working with Shiyu Luo from the Cincinnati Children's Hospital have now discovered evidence that mitochondrial DNA can also be passed on from father to offspring. On the trail of this unexpected inheritance mechanism, the team discovered the DNA of a four-year-old boy. This small patient was suspected of having mitochondrial disease - a disease caused by mutations in the mitochondrial genome.

To get to the bottom of this suspicion, the boy's DNA was sequenced and analyzed. It turned out that an unusually large number of gene variants were mutated in only part of the mitochondria of the cell, while this corresponding section of the genome was normal in other mitochondria. This phenomenon is known as heteroplasmia. The ratio of normal and mutated DNA is decisive for whether the mutations actually cause symptoms.

From mother and father

Because the extent of heteroplasmia in the boy was so unusual, the researchers then also examined the mitochondrial genome of his family members - including those of his mother and grandparents. They made a surprising discovery in their mother: their heteroplasmic genetic variants could not be explained by an exclusively maternal inheritance. Instead, she appeared to have inherited 21 of these variants from her mother and ten more from her father.

The boy and his two sisters, in turn, seemed to have inherited all mitochondrial DNA from their mother, according to the current pattern. Was the paternal inheritance a strange individual case - or was Luo's team possibly even made a mistake? Apparently no: Additional, independent DNA analyzes confirmed the abnormal result.

Unusual mode of inheritance

But not only that: the scientists finally found the same phenomenon in other family members and even other families. Specifically, they found evidence of paternal inheritance of mitochondrial DNA in 17 people from a total of three different, unrelated families. “Our work thus challenges fundamental assumptions about mitochondrial inheritance,” they write.

Inheritance of the mitochondrial genome from both parents was previously only known from some yeast species and, in exceptional cases, from Drosophila flies, mice and also sheep, as the researchers report. It is now clear that this phenomenon also occurs in humans: “The rule is still inheritance through the mother. In some cases, however, mitochondrial genetic material can also be passed on from the father to the children. "

Decipher mechanisms

According to the team, deciphering the mechanisms behind this unusual inheritance could not only provide new insights into how mitochondrial DNA is transmitted from parents to offspring. "This may even result in new therapeutic approaches for hereditary mitochondrial diseases," the researchers conclude. (Proceedings of the National Academy of Sciences, 2018; doi: 10.1073 / pnas.1810946115)

(PNAS, 11/27/2018 - DAL)

November 27, 2018