MITOCHONDRIAL INHERITANCE: APPLICATIONS, PATHOLOGIES, PREVENTIONS - BIOLOGY - 2025

The mitochondrial inheritance is the transmission of mitochondrial DNA through the organelle called "mitochondria" and occurs from parent to his descendants. Typically, inheritance occurs only from maternal mitochondria, in a "matrilineal" fashion.

Shiyu Luo and colleagues, however, published an article in January 2019 in which they found evidence that, on rare occasions, mitochondrial DNA can be inherited from both parents.

Mendelian inheritance patterns vs Mitochondrial inheritance patterns (Source: BQmUB2011167 via Wikimedia Commons)

Most of the genetic material in eukaryotic cells is found within the cell nucleus. However, a small part of DNA is found inside the mitochondria.

The genetic material inside this organelle is known as mitochondrial DNA, which is organized in a circular chromosome, which in mammals is between 16,000 and 16,800 base pairs in length.

Mutations in mitochondrial DNA have been observed to cause severe disease in individuals and in most cases the diseases are only inherited from mother to child, when maternal mitochondria have mutations in their DNA.

All the mitochondria of the descendants come from a small group of mitochondria present in the ovule when the moment of zygote formation occurs (fusion of ovum and sperm) therefore, in most cases the mitochondria of the fetus are only inherited from his mother.

Fusion of gametes and transfer of mitochondria

At the time of fertilization of the ovum (female gamete), the sperm or male gamete contributes a few mitochondria to the developing embryo.

This contribution occurs at the moment of contact of the sperm with the plasma membrane of the ovule, since both membranes fuse and the sperm enters the cytoplasm of the ovule, emptying its internal content there.

In most taxa of the animal kingdom there is a "tendency" towards inheritance in a clonal or uniparental form of mitochondria and mitochondrial DNA (almost always with respect to mothers). In some families of animals there are destruction mechanisms for the paternal mitochondria transmitted by sperm cells.

The ovum in mammals has hundreds of mitochondria, which represent about 1/3 of the total DNA that these sex cells have; while the sperm only has a few in an intermediate region between the flagellum and the head.

Human eggs have more than 100,000 copies of mitochondrial DNA; meanwhile, the sperm has only about 100, but the amount varies depending on the species in question.

This makes it evident that the vast majority of the mitochondria in the cells of the descendants are of maternal transmission. Therefore, if the mitochondria of the ovules present harmful or deleterious mutations, these mutations will be transmitted to their descendants.

Biparental inheritance

The scientist Hutchinson, in 1974, was one of the first to affirm that the inheritance of mitochondria occurred in a strictly maternal (matrilineal) way. However, at the beginning of the 20th century, White and colleagues observed that in some mussels the mitochondrial inheritance was not strictly maternal.

Later, in 2008, this observation in mussels was designated as a type of "heteroplasmy", which refers to the "leakage" of mitochondria and paternal mitochondrial DNA into offspring.

Many more observations identified the presence of paternal mitochondria and mitochondrial DNA in mussels as natural.

Shiyu Luo and colleagues identified three people from three human families with unusual mitochondrial DNA heteroplasmy. These heteroplasmias could not be explained by the descent of the maternal mitochondrial DNA, so these authors performed next-generation sequencing of the mitochondrial DNA of both parents and both grandparents of the three people.

In this way, the unusual heteroplasmy was identified as a product of the contribution of mitochondrial DNA from both grandparents, the grandmother and the grandfather. In addition, the authors identified two additional unrelated families exhibiting biparental mitochondrial transmission.

This research was the first report on mitochondrial inheritance in a biparental way in humans.

Luo et al. Suggest that heteroplasmy due to paternal mitochondrial DNA transmission is missed in diagnoses when it does not cause any disease in the individuals who carry it.

Applications

Mitochondrial DNA was introduced in population genetics, phylogeny and evolutionary studies by Dr. John C. Avise in 1979 and today this is one of the most powerful tools for studying population genetics of all living beings.

By tracing the genealogy of human mitochondrial DNA, an immense amount of genetic studies have been performed to try to pinpoint the origin of humanity.

Even, based on maternal mitochondrial DNA, it has been determined that all people in the world can be classified into around 40 different groups of mitochondrial haplotypes, closely related to different geographical areas of the world.

Many commercial houses such as "Oxford Ancestor" offer to trace all the ancestors of people using the inheritance of mitochondrial DNA.

The founder of the Oxford Ancestor, Bryan Sykes, used mitochondrial DNA to classify all Europeans into clans founded by the "Seven Daughters of Eve." This is the title Sykes assigned to a book he wrote trying to trace the origin of all Europeans.

In his book, Bryan Sykes follows the mitochondrial inheritance of all European citizens through sequencing the mitochondrial DNA of thousands of people, locating the origin of all Europeans in seven women who existed before the last ice age, 45,000 years ago.

Pathologies and preventions

Harmful mutations in mitochondrial DNA genes cause multiple diseases at the systemic level. These mutations can be transmitted by mitochondrial inheritance through the mother and, rarely, the father.

A mutation in the mitochondrial DNA can cause problems due to the absence or damage of the enzymes involved in cellular respiration. This damage leads to a reduction in the ATP supply of the cells, causing the body's systems to malfunction.

However, on many occasions people inherit various types of mitochondria from their mothers, some functional and others defective; therefore, mitochondria with functional genes can compensate for the malfunction of faulty mitochondria.

Mode of transmission of mitochondrial pathologies via the «matrilineal» pathway (mitochondrial inheritance) (Source: ghr.nlm.nih.gov via Wikimedia Commons)

Currently, research is being done to transfer cell nuclei that can allow women who suffer from diseases caused by harmful mutations in the mitochondria to have healthy children.

The method to transfer nuclei consists of extracting the cell nucleus from the mother's ovum with the affected mitochondria and inserting it into normal donated ovules, from which the cell nucleus has been previously extracted.

Subsequently, the ovum can be fertilized by sperm from the patient's partner in vitro. This technique has generated controversy because the conceived fetuses would have the DNA of three different parents.

References

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