Extranuclear inheritance of organelles

Of course, chloroplasts are not the only DNA-containing organelle inherited through gamete cytoplasm. Mitochondria also contain DNA, and they show similar patterns of uniparental and biparental inheritance. In fact, because most animals lack chloroplasts, the main form of cytoplasmic inheritance in animals is via mitochondrial DNA, which is known as mtDNA.

The first people to capture images of DNA “fibers” in mitochondria were Margit and Sylvan Nass in 1963. With a powerful electron microscope, they were able to zoom in on part of a mitochondrion and take a photograph at a magnification of 150,000X. In doing so, the Nasses noticed a black threaded material inside mitochondria that would disappear after exposure to an enzyme (deoxyribonuclease) that specifically dissolved DNA. This was the first visual and chemical evidence that DNA existed in mitochondria.

Since the Nass experiments, interest in mtDNA has expanded greatly. Scientists now know that within a single cell, there can be thousands of mitochondria, and each mitochondrion contains from two to ten copies of mtDNA. During cell division, the mitochondria aggregate randomly into progeny cells. This means that each cell can theoretically contain a different mixture of normal mtDNA and mutated mtDNA, which can in turn generate a variety of phenotypes (Fig.2). But are these mtDNA mutations anything more than a sideshow to the main events of nuclear function? Indeed they are. Mutations in mitochondria can have very serious effects, and they are even the basis for several diseases. Mitochondria’s crucial role as the main producer of ATP within cells means that malfunctions in these organelles are truly bad news.

Fig.2 : Cytoplasmically inherited characteristics frequently exhibit extensive phenotypic variation because cells and individual offspring contain various proportions of cytoplasmic genes. Mitochondria that have wild-type mtDNA are shown in red; those having mutant mtDNA are shown in blue.

Extranuclear inheritance of mitochondria has been tracked in families that carry defective mitochondrial genes. Some of the diseases caused by defective mitochondria particularly affect muscle tissue, as muscle uses ATP and mitochondria are cellular producers of this substance. One such condition is an inherited disorder called progressive external ophthalmoplegia (PEO). Spelbrink et al. (2001) analyzed multiple pedigrees of families affected by PEO, and they analyzed the mitochondrial genes along with the inheritance pattern of the disease. Eventually, the researchers noticed that the mtDNA of those individuals affected with PEO showed many more deleted sequences than the mtDNA of unaffected individuals. Next, the team tried to figure out what these deletions meant for mitochondrial function. After taking blood samples from 12 different families affected with PEO, they extracted mtDNA from blood lymphocytes and screened it for common patterns in affected and unaffected individuals. They found that PEO carriers had 11 different deletions in the coding sequence for a mitochondrial protein that appeared to be involved in mtDNA replication. They named this protein Twinkle, because it is distributed all over mitochondria like a constellation pattern in the night sky. The investigators concluded that Twinkle is likely a DNA helicase protein involved in maintaining the integrity of mtDNA as it replicates. Therefore, although Twinkle is encoded by nuclear DNA, it affects the transcription of mtDNA (Spelbrink et al., 2001). In other words, when it comes to PEO, both nuclear and mitochondrial DNA are involved in the inheritance of a single disease.