Question

My understanding is that genes that are functionally important are more highly conserved. The DNA coding for ribosomal RNA is one example of that. I was surprised to find out that mitochondrial DNA had a high mutation rate. I'm mostly concerned with metazoan mitochondrial DNA, and more specifically, animal or mammalian mitochondrial DNA.

I've tried searching why exactly that is, and so far, from what I understand, it could be:

the lack of DNA repair enzymes in the mitochondria
the production of free radicals in the oxidative phosphorylation process leading to more point mutations
But how would the cell with these somatic mutations (or embryo with inherited germ line mutations) survive then? Are these mutations only passed down in the non-coding regions on the mtDNA, and the coding regions are indeed highly conserved?

I've also read that:

the high mutation rate refers more to the shifts in gene order on the chromosome
critical genes in the mitochondria migrate to nuclear DNA
I think I could be missing some understanding of wobble base pairing in the mitochondrial translation system, or some quirks of the bacterial DNA, etc. I've hoping for a relatively complex and in-depth explanation of this. Thank you.

Answer 1

The high mutation rate in metazoan mitochondrial DNA can be attributed to several factors, including the lack of DNA repair enzymes, the production of free radicals, and the presence of heteroplasmy. However, coding regions in mitochondrial DNA are generally conserved, and critical genes have migrated to nuclear DNA.

Step-by-step explanation:

The high mutation rate in metazoan mitochondrial DNA can be attributed to several factors:

• Lack of DNA repair enzymes: Mitochondria have limited DNA repair mechanisms compared to the nucleus. This means that errors in DNA replication or damage from oxidative stress are not efficiently repaired, leading to a higher accumulation of mutations.
• Production of free radicals: The process of oxidative phosphorylation in mitochondria generates free radicals as byproducts. These free radicals can cause DNA damage and mutations.
• Heteroplasmy: Mitochondria can exist in a state called heteroplasmy, where multiple alleles are present within a single cell. This condition allows for a certain level of variability in the mitochondrial DNA without affecting the overall function of the cell.

While there is a higher mutation rate in mitochondrial DNA, it is important to note that this mainly affects the non-coding regions. The coding regions, which contain genes that are functionally important, are generally conserved. Critical genes in the mitochondria have also been found to migrate to the nuclear DNA over the course of evolution, further ensuring their conservation.