Mitochondria are important organelles for generating energy in the cells. They have a unique genome. In some species, the mitochondrial DNA is linear. Whereas in some species it is circular. The endosymbiont theory revealed that the mitochondria and chloroplasts originated as prokaryotes. Later on, they invaded the eukaryotic cells to establish a symbiotic relationship. Mitochondria are involved in cellular respiration which is a process of oxidization of food molecules. Mainly, the oxidization of glucose gives rise to carbon dioxide and water. The energy released in this process is known as ATP (Adenosine Triphosphate). Thus, mitochondria are also known as energy powerhouses. Till now we only knew the genes present in the nucleus. We have studied the structure and expression of the nuclear genes. Years later the discovery of the nuclear genes, the scientists found that there was something else beyond the Mendelian pattern of inheritance. Mitochondria also controlled a few traits. The genes present in the cytoplasmic organelles such as mitochondria and chloroplast are known as extra-nuclear genes. They are alternatively known as Non-Mendelian genes because they do not follow Mendelian inheritance pattern.
Image 1: Mitochondrion and its DNA
The Mitochondrial Genome:
The origin of the mitochondrial DNA is of bacterial or prokaryotic origin. Thus, it shows similar replication and gene expression features. A wide structural variation persists in the eukaryotic mitochondrial genome. The complete sequences of mitochondrial DNA are now known to us. The structure of the mitochondrial genome is highly conserved in the mammals. Though mitochondria have their separate genomes, they are not completely self-operative. In some cases, they may also require nuclear gene products for carrying out their specific functions. The copy number of the mitochondrial genome in the oocytes is extremely high. Fertilization is a process in which the sperm and the egg fuse with each other. During this process, the mitochondria present in the sperm do not get transferred to the oocyte. Thus, the zygote contains the mitochondria of the oocyte. Thus it follows a maternal pattern of inheritance.
Description of mitochondrial DNA:
The mitochondrial DNA is double-stranded, supercoiled and circular. The mitochondrial DNA is also known as mtDNA. It codes for 37 genes in humans, and 35 genes in S. cerevisiae. The mitochondrial DNA consist of 16.6 kilobases nucleotide base pairs. The GC content of mtDNA differs from that of the nuclear DNA. Many genes in the mitochondria encode for the enzymes involved in the oxidative phosphorylation. Extranuclear processes require many such enzymes. For some of the processes, the nuclear genes may not be sufficient to encode proteins or enzymes. Thus, mitochondrial genes play a crucial role in synthesizing enzymes that catalyze reactions for generation of energy.
An abnormality in the mitochondrial genes may lead to mitochondrial disorders. The mitochondrial DNA does not associate with the histone proteins. There is very little extragenic or repetitive DNA in the mitochondrial genome. The human mitochondrial genome is small and compact. The genes are very close to each other with a very little space between them. In yeast, the mitochondrial genome consists of widely spaced genes. Mitochondrial genomes are studied using metagenomics.
Just like the nuclear DNA, the mitochondrial DNA also undergoes a semi-conservative type of replication. Mitochondrial DNA also requires DNA polymerases to carry out the process of replication. These enzymes are known as mitochondrial DNA polymerases. The mtDNA replication occurs throughout the cell cycle. Unlike nuclear DNA replication, the mtDNA is not S-phase specific. The displacement loop or D-loop model is studied. The two mtDNA strands show different densities. The bases are spaced unequally on the strands. The unequal spacing or distribution of bases creates heavy and light strands. Letter ‘H’ is used to denote the heavy strand. Letter ‘L’ is used to denote the light strand of the mitochondrial DNA. The mtDNA is supercoiled up to a hundred coils. The uncoiling takes place during the initiation of replication. The synthesis of H strand starts at the origin of replication. Formation of a ‘D’ shaped loop takes place. The loop expands further to synthesize a new light strand. Synthesis of the light strand starts at the second replication origin. Thus, mitochondrial DNA follows a continuous type of replication for both the strands. After completion of the replication, the supercoiling of the two circular mtDNAs occurs. The heavy and light strands consist of mitochondrial protein-coding genes.
Image 2: Mitochondrial inheritance
Investigation of the genetic relationships:
Mitochondria exclusively follow maternal inheritance. It means that they are inherited only from the female gamete, the oocyte. Thus, the oocyte is the major contributor of the cytoplasm. The mitochondrial DNA analysis can be used to assess the genetic variability of a given population. The diseases caused due to maternal inheritance get detected using information related to mitochondrial DNA mutations. Finding the ancestors and relatives of an individual may be easier.
The story of the Tsar and Tsarina:
The Bolsheviks executed the Tsar and his family in the eighteenth century. However, one of the Tsar’s three daughters, Princess Anastasia managed to escape from the execution. After many years, a woman claimed herself as Anastasia. She lived in the United States for many years as Anna Anderson. The Tsar’s family members’ mtDNA samples were used to study their relationships. Thus mtDNA analysis helped to reveal the true relationships in the Romanovs.
Human ancestry linked to mtDNA studies:
Various studies revealed that genetic recombination is uncommon in the mitochondrial DNA. Thus it is similar to the Y chromosome. The mtDNA is a good genetic marker for tracing the human ancestry. Human mitochondrial DNA undergoes evolutionary changes in the sequences at an approximately constant rate. The statistical figures suggest one change per mitochondrial lineage every three thousand to four thousand years. Analyzing mitochondrial DNA from human bones provides a good number of lineal history evidence. Just as the Y chromosome is inherited only through the father, the mitochondrial DNA is inherited only through the mother. Thus mitochondrial DNA exhibits itself as a family album with pictures of the members. It helps to identify the degree of kinship and the familial origin.
Various studies report a pre-historic migration of human population into North America. The first mtDNA study revealed that Native Americans descended from the Asian ancestors many years ago. They found four distinct mitochondrial haplogroups. Another study revealed the African origin of the modern human population. You might know the story of an African woman (called as Mitochondrial Eve), who lived many lakhs of years ago. She passed on her mitochondrial DNA to future generations. Similarly, the man who passes on the Y chromosome was known as Y chromosome- Adam. Hence, human origin is a topic of debate.
The sequences from the bones of the Neandertal-human were analyzed. PCR analysis was used to obtain DNA sequences from the bone specimens. The relationships between the Neandertals and modern humans were studied using phylogenetic trees. Molecular information such as mtDNA sequences and immunological data were studied. Thus, mitochondrial DNA provided a crucial role in tracing the human ancestry and origin.
References:
[1] Medical genetics, G.P. Pal
[2] Mitochondrial DNA- Wikipedia
[3] Genomics of Chloroplasts and Mitochondria, Ralph Bock, Volker Knoop
[4] Introduction to Genomics, Arthur Lesk
[5] Biomolecular Archaeology: An Introduction, T. A. Brown, Keri Brown
[5] Biomolecular Archaeology: An Introduction, T. A. Brown, Keri Brown
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