6.13: Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by the complete absence of introns. Also, their genes are very closely spaced and some of them even have overlapping regions. D-loop is the most important regulatory non-coding region of mitochondrial DNA, which also contains the origin of the replication for the H-strand. Mitochondrial genetic code differs from nuclear DNA code with respect to a few codons. For example, codon UGA, AUA, and AGA/AGG codes for STOP codon, isoleucine, and arginine, respectively, in nuclear DNA while the same codons codes for tryptophan, methionine and STOP codon, respectively, in animal mitochondrial DNA.

Replication of nuclear DNA is coordinated with the cell cycle and must be finished before cell division occurs. Another characteristic feature of the mitochondrial genome is its relaxed DNA replication, where unlike nuclear DNA, replication is independent of the cell cycle and can go on in daughter cells even after cell division.

Maternal Inheritance

In mammals, mitochondrial DNA gets inherited only from the mother’s oocyte as the mitochondria present in the sperm are selectively degraded by a ubiquitin-mediated pathway in the zygote. Mutations in mitochondrial genes can result in diseases such as Leber’s hereditary optic neuropathy or Leigh syndrome; therefore, if the mother carries such mutations, her offspring can inherit these diseases. Recently, new therapies such as mitochondrial replacement can allow the birth of an unaffected child to an affected mother. The nucleus of the mother’s oocyte is transferred to an enucleated oocyte of a healthy donor with normal mitochondria before fertilization. This technique has led to the birth of the so-called “three-parent baby,” who did not inherit the mother’s mitochondrial disease.

Mitochondria produce energy-rich ATP molecules and are the only organelles in the animal cell to have their own genetic system.  

The present-day mitochondrion is thought to have evolved from an aerobic bacterium, which formed a mutually beneficial, or symbiotic, association with its predator. 

Over time, many genes from this bacterium were transferred to the nuclear DNA of the host cell and other genes were lost, leaving behind a small but independent mitochondrial DNA.

Some cells, like muscle cells, can contain hundreds of mitochondria, while others, like red blood cells, do not contain any. Each mitochondrion can contain up to 10 copies of the mitochondrial DNA.

Mitochondrial DNA is a closed, circular molecule varying in length from 14,000 to 20,000 bps, in animal cells, as compared to millions of base pairs present in nuclear DNA. 

This mitochondrial DNA encodes only a small number of biomolecules: the 16S and 12S rRNAs, up to 25 tRNAs, and 13 respiratory chain proteins. Nuclear DNA codes for the remaining proteins required for mitochondrial function.

Around 93% of the mitochondrial DNA codes for proteins, unlike nuclear DNA, where only about 1 percent are coding regions. This is partially because introns, which are a regular feature of eukaryotic DNA, are absent in mitochondrial DNA.  

Several sequences of the genetic code are translated differently depending upon the type of DNA. For example, the codon UGA codes for tryptophan in mitochondrial DNA, whereas it is a stop codon in nuclear DNA.

Mitochondrial DNA has a faster rate of evolution than that of nuclear DNA due to the mutation rate in mitochondrial DNA being greater than 10 fold higher. 

This is because mitochondrial DNA is not protected by histones like that of nuclear DNA and is exposed to reactive oxygen species generated during mitochondrial reactions. Additionally, it also has less efficient DNA repair machinery.

Transfer of mitochondrial DNA always happens from mother to offspring. This is known as maternal inheritance. 

Maternal inheritance occurs because, after fertilization, the few mitochondria present in sperm are degraded while the many mitochondria in the ovum remain present in the embryo and are passed onto all the cells in the offspring.