- If both paternal and maternal mtDNA are present in the cell, it would be a lethal combination due to numerous mutations (Ankel-Simons, Cummins, 1996; Brandon et. al 2005; Danan, 1999; Foley, 2003; Hayashida et al, 2005; Kunchithapadam, 1995; Whittle, Jonston, 2002);
- If one tissue has maternally inherited mtDNA and another one shows paternal mtDNA in a normal organism (not a hybrid), it could cause:
- Failure of T- and B-cells’ recognition of specific tissues;
- Increased mutation rate, different for all the tissues of the organism;
- Different ATP production. ATP coming from paternally inherited mtDNA may not be recognized by cellular structures, causing a dysfunction of ATP- dependent reactions;
- The organism would undergo a series of devastating diseases (Altziemers’ disease, Parkinson disease, etc) and most probably would be sterile (Ankel-Simons, Cummins, 1996; Brandon et. al 2005; Cables, 2002; Danan, 1999; Hayashida et al, 2005).
Compared to the stable oocyte’s mtDNA, father’s mtDNA comes with the sperm and can be damaged on the way to the oocyte. Paternal mitochondria are carried in the
sperm tail and provide ATP for sperm movement (Ankel-Simons, Cummins, 1996; Brandon et. al 2005; Danan, 1999; Foley, 2003; Hayashida et al, 2005). Several questions arise here:
- Does the sperm tail stay outside the oocyte when the acrosome reaction takes place?
In fact, recent studies showed sperm tail penetration after the acrosome reaction in mammals. While the sperm head releases the set of chromosomes to the egg’s nucleus, the tail is still attached. It is not certain whether lysosomes destroy the tail and where it disappears when chromosome merge is complete. So, the paternal mitochondria have some time within the egg when they potentially could distribute their mtDNA (Ankel-Simons, Cummins, 1996; Danan, 1999; Foley, 2003; Hayashida et al, 2005; Kunchithapadam, 1995).
- If the sperm tail penetrates, does paternal mitochondria stay within the egg and automatically become inherited?
No, it does not. The sperm is marked with ubiquitin – specific protein, which codes for destruction. Thus, when sperm tail remains in the egg for the time of male’s chromosome set transfer, it is digested by cellular structures. Paternal mitochondria do not remain in the egg unless:
- There is a mistake in ubiquitination – sperm is not marked when developed,
- The cellular structures of the egg do not recognize foreign mitochondria (Ankiel-Simons, Cummins, 1996; Foley, 2003).
Several experiments were conducted on sperm penetration and acrosome reaction to show the impossibility for a normal organism to inherit paternal mtDNA. Intercytoplasmic sperm injection (ICSI) (Danan, 1999) involves a sperm being placed directly into the cytoplasm of the egg, where it does not go through acrosome reaction. The result is the same: chromosome sets are merged and the sperm tail is destroyed. This experiment supports the ubiquitination – the sperm is condemned to destruction after it carries out its main function of passing on chromosome set (Danan, 1999; Hayashida et al 2005 Kunchithapadam, 1995).
Recent mammalian studies showed that paternally vs. maternally inherited mtDNA ratio is 1:1,000 to 15:1,000 (Danan, 1999). Considering mammals and humans closely related on the mitochondrial level we would assume these stats to be the same for human maternal offspring as well. This could mean that there is an occasional paternal mtDNA expression in some cells of eukaryotic organisms, but it is so small that it does no affect the overall cellular processes. Separately studied human offspring, however, showed no inheritance of paternal mtDNA (poor data) (Danan, 1999; Hayashida, 2005).
- There is no evidence for paternal and maternal mtDNA fusing together and forming new mtDNA. mtDNA reproduces asexually by splitting into two daughter cells, which are not always identical:
- Rare maternal cell’s mutations can be expressed in one of the daughter cells, while another daughter cell does not carry any mutations. Thus a child can end up carrying both normal and mutant mtDNA – this phenomenon is
called heteroplasmy (Cables, 2002; Danan, 1999; Foley, 2003);
- Paternal and maternal mtDNA cannot be fused together because of the asexual reproductive process each one undergoes separately. It’s easier to carry on a specific stable maternal set of mtDNA, which it is not mixed with paternal mtDNA set (like in the chromosomes).
Although the hypotheses discussed above state that sperm mtDNA cannot be inherited, the point 2.2 and some other exceptions can potentially allow for paternal mtDNA inheritance:
Mutations inherited in the male (let’s say he received one of the daughter mtDNA with mutations) are expressed in chromosome set and gene expression. So, when this male transfers his 23 chromosomes to the female, automatically there are two possibilities (Ankel-Simons, Cummins, 1996; Foley, 2003):
- The new organism’s chromosome expresses the abnormality expressed in the father,
- The new organism is normal.
Thus, mtDNA mutations can be carried on from fathers to offspring through chromosome gene expression. Sometimes the chromosome will code for the abnormality expression in a specific tissue, for instance a muscle tissue.
- Sometimes an incorrect chromosome gene expression can result in recombining both maternal and paternal mtDNA in a way that:
- The egg will not recognize paternal mtDNA when it enters the egg after the acrosome reaction and allow for both maternal and paternal mtDNA in cells;
- Chromosomes will code for the destruction of half of the maternal mtDNA;
- Genes will make half of the maternal mtDNA behave as a paternal mtDNA (poor data collected, but it is still possible) (Brandon et. al 2005; Cables, 2002; Foley, 2003).
A recent case study was performed on a man, who was severely intolerant to the exercise. The study showed that his muscle tissue had 0.7% of recombined paternal and maternal mtDNA. It is not clear whether this phenomenon was caused by leakage of paternal mtDNA into the egg or chromosome coded for partial paternal mtDNA expression. This case showed, however, that mtDNa recombination is possible (mitochondria has a functional recombinase) (Paendorf, Stoneking, (11/20/2005)) although the way these organells can fuse and exchange the contents is not known. Besides, this man possessed heteroplasmic maternal mtDNA (both mutant and normal), which could also make such rare recombination possible and so severe. In the absence of heteroplasmic mtDNA recombination would probably be less severe or would not take place (Ankel-Simons, Cummins, 1996; Brandon et. al 2005; Cables, 2002; Danan, 1999; Foley, 2003; Kunchithapadam, 1995)
This paper has looked at and compared the rates at which maternal and paternal mtDNA molecules are inherited. Today maternal mitochondrial inheritance is considered
a rule to mitochondrial DNA heritage. It allows for precise studies based on mitochondrial lineages:
- If the mtDNA of two specimen is nearly identical – they are most probably siblings;
- If the mtDNA has many base pair differences – it has been a long time since the lineages with closely related mitochondrial DNA diverged.
Nowadays, there are many studies that try to figure out potential diseases resulting from mitochondrial abnormalities and their causes. Although maternally inherited mtDNA is dominant in the cells of the human organism, hypothesis #4 shows that some paternally inherited mtDNA occur in mammalian organisms (not necessarily in humans though). The reason for that is unknown, but we could presume that there are some spontaneous deletions and mistakes in the egg when destroying the sperm mitochondria, as well as in chromosome set inherited from father (Ankel-Simons, Cummins, 1996; Brandon et. al 2005; Cables, 2002; Danan, 1999; Foley, 2003; Hayashida et al, 2005; Kunchithapadam, 1995; Paendorf, Stoneking, (11/20/2005);
So far we can assume that paternal mtDNA inheritance is negative rather that positive in the organism due to its high mutational rate and diseases that are potentially caused by paternal mtDNA inheritance.
Almost all eukaryotic organisms possess matrilineal mtDNA inheritance potentially due to the same reason as humans do except of hybrids, which are not well studied. Hybrids are sterile most of the time (like a mule) (Ankel-Simons, Cummins, 1996; Brandon et. al 2005), a pattern that is observed in humans when they inherit
mitochondria from a father. It is not certain though whether sterility is caused by mitochondrial abnormality or some other reason. Science benefits from matrilineal mtDNA inheritance in both mammals and humans (and other organisms that have mitochondria) because it can trace down lineages of organisms and figure out how they are/were linked and where they came from.
In conclusion, we must realize that there can be other reasons explaining maternal mitochondrial inheritance. Diseases that we think are caused by paternal mtDNA can have more factors apart from mitochondria abnormalities causing them. It is a hard to state that the only correct rule is the rule of strictly maternally inherited mtDNA, when there is so much uncertainty in our observations. We harbor more than one haplotype of mtDNA in our bodies (ratio 1:1,000 to 15:1,000; potential mixing of two different lineages, etc. – examples of more than one mtDNA lineage), but how it comes to existence is not known yet (Danan, 1999; Hayashida, 2005).
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