Payne, B. A. et al. (2013) present evidence that a low level of heteroplasmic mtDNA exists in all tested healthy individuals.
What are two likely sources of such heteroplasmy?

The first person in a family to exhibit Leber hereditary optic neuropathy (LHON) was II-3 in the pedigree shown below, and all of her children also exhibited the disease. Provide two possible explanations as to why II-3's mother (I-1) did not exhibit symptoms of LHON.

Mutations in mitochondrial DNA appear to be responsible for a number of neurological disorders, including myoclonic epilepsy and ragged-red fiber disease, Leber's hereditary optic neuropathy, and Kearns-Sayre syndrome. In each case, the disease phenotype is expressed when the ratio of mutant to wild-type mitochondria exceeds a threshold peculiar to each disease, but usually in the 60 to 95 percent range.

Compared with the vast number of mitochondria in an embryo, the number of mitochondria in an ovum is relatively small. Might such an ooplasmic mitochondrial bottleneck present an opportunity for therapy or cure? Explain.

Mutations in mitochondrial DNA appear to be responsible for a number of neurological disorders, including myoclonic epilepsy and ragged-red fiber disease, Leber's hereditary optic neuropathy, and Kearns-Sayre syndrome. In each case, the disease phenotype is expressed when the ratio of mutant to wild-type mitochondria exceeds a threshold peculiar to each disease, but usually in the 60 to 95 percent range.

Given that these are debilitating conditions, why has no cure been developed? Can you suggest a general approach that might be used to treat, or perhaps even cure, these disorders?

In 1918, the Russian tsar Nicholas II was deposed, and he and his family were reportedly executed and buried in a shallow grave. During this chaotic time, rumors abounded that the youngest daughter, Anastasia, had escaped. In 1920, a woman in Germany claimed to be Anastasia. In 1979, remains were recovered for the tsar, his wife (the Tsarina Alexandra), and three of their children, but not Anastasia. How would you evaluate the claim of the woman in Germany?

Payne, B. A. et al. (2013) present evidence that a low level of heteroplasmic mtDNA exists in all tested healthy individuals.

What genetic conditions within a given mitochondrion are likely to contribute to such a variable pool of mitochondria?

The dodo bird (Raphus cucullatus) lived on the Mauritius Islands until the arrival of European sailors, who quickly hunted the large, placid, flightless bird to extinction. Rapid morphological evolution such as often accompanies island isolation had caused the bird's huge size and obscured its physical resemblance to any near relatives. However, sequencing of mitochondrial DNA from dodo bones reveals that they were pigeons, closely related to the Nicobar pigeon from other islands in the Indian Ocean. Why was mitochondrial DNA suited to the study of this extinct species?

The mtDNA accumulates mutations at a rate approximately ten times faster than nuclear DNA. Thus geneticists can use mtDNA variations as a 'molecular clock' to study genetic variation and the movement of ancestral human populations from Africa to different areas of the world more than 125,000 years ago. Propose an explanation for how an analysis of mtDNA can be used to construct family trees of human evolution.

Because offspring inherit the mitochondrial genome only from the mother, evolutionarily the mitochondrial genome in males encounters a dead end. The mitochondrial genome in males has no significant impact on the genetic information of future generations. Scientists have proposed that this can result in an accumulation of mutations that have a negative impact on genetic fitness of males but not females. Experiments with Drosophila support this possibility. What experimental data or evidence would you want to evaluate or consider to determine if an accumulation of mtDNA mutations negatively impacts the fitness of males of any species?