Mitochondrial DNA in Human Migration is extremely significant as it contains 99.99 % of maternally inherited genes. Thanks to the advancement in molecular techniques.
Mitochondrial DNA, though it represents a small fraction of the total size of the genome, it has emerged as one of the most popular molecular markers for assessment of diversity and evolutionary tracks.
The Consistently Migrating Humans
Since origin, Homo sapiens are accustomed to continuous and extensive migration, inhabitation at various geographical locations, and adaptation to different climatic and environmental conditions. Different scientific pieces of evidence suggest that the entire human race migrated out of Africa.
The prolonged movement and settlement diversified modern humans into different races, populating themselves with respect to their social, cultural, and linguistic identity. But this diversity has deep incursion into the genetic root.
Advancements in Molecular Techniques
Since two individuals cannot have the same genotypic and phenotypic identity, except for identical twins, the rich information revealed from the genetic component of every individual is an excellent resource to study the diversity in humans, their route of migration, and predisposition of various diseases.
With the development of new and advanced molecular techniques, genetic study and analysis has become a lot easier and fast. In less than half a century, the concept of molecular markers has completely revolutionized our perception of nature, and contemporarily, the new marker system is evolved too.
Various genetic marker systems (RAPD, RFLP, AFLP, CBDP, iBPS, SNP, VNTR, STR, etc.) are available to assess genetic variation among and within the populations.
Fast Track>>> A molecular marker is a specific molecule that can be studied to track certain characteristics of its source. Genetic marker, a molecular marker, is a gene or DNA sequence on a known location in a chromosome that can be studied to reveal genetic traits, disorders, or evolutionary history, etc.
Additionally, many uniparental [Y-haplogroup, mitochondrial DNA (mtDNA)], and biparental markers [human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR)] are the promising ones for genetic diversity studies.
Mitochondria, to date, have played a significant role in the study of aging, apoptosis, cell energetics, and various pathological conditions. But very recently, this semi-autonomous organelle has been found to possess specific characteristics that make them very useful in tracing evolutionary events.
Mitochondrial DNA (mtDNA), being present in massive copies in cells, make it more accessible from residues of fossils and more comfortable to study, as compared to nuclear DNA (nDNA).
The Mitochondrial Genome
The mitochondrial genome contains 99.99 % maternally inherited genes, while a small contribution (0.01 %) is inherited from the male parent.
The total amount of mtDNA in a cell depends on the number of mitochondria, the size of the mtDNA, and the number of mtDNA per mitochondrion. Each of these parameters varies significantly between different cell types.
Human mtDNA, a double-stranded circular molecule, is the smallest known mtDNA that has 16,569 base pairs in length and contains genetic code for 37 very crucial genes. Of these, 13 genes are responsible for producing respiratory chain protein subunits, 22 genes encode for 22 transfer RNAs (tRNAs), the remaining two genes encode for two ribosomal RNAs (rRNAs) and one non-coding displacement loop (D-loop) region.
Mitochondrial DNA, though it represents a small fraction of the total size of the genome, it has emerged as one of the most popular molecular markers for assessment of diversity and evolutionary tracks.
Why mtDNA is a Preferred Molecular Marker for Tracking Human Migrations
- high mutation rate as compared to the nuclear genome which results in the existence of different mtDNA variants in an individual defines the significance of Mitochondrial DNA in Human Migration.
- lack of recombination,
- stability of double-stranded mtDNA which makes it possible to retrieve even from the degraded specimens,
- natural and non-invasive sample collection such as buccal swabs and mouthwash,
- the uniparental transference to descendants, and
- their non-disarrayed nature in the evolutionary mechanism.
In addition to these features, the ability of mtDNA to effortlessly recoup from ancient DNA, combined with its less effective population size, is responsible for the high frequency of deleterious mtDNA alleles within species and make them more susceptible to genetic drift and population bottlenecks.
Lack of recombination, inefficient DNA repair, high rate of mutation, and ceaseless deleterious alleles lead to the accumulation of linkage disequilibrium in the mitochondrial genome, which partially restrain genetic variation for fitness at individual loci thereby reducing the efficacy of natural selection.
However, not all regions of the mitochondrial genome evolve at the same rate. It is the non-coding, triple-stranded part produced by the synthesis of a short fragment of H-strand DNA (Heavy Strand), the D-loop, which is the most changing region. D-loop is the most polymorphic, control region of the entire human mtDNA genome. It consists of two hypervariable regions (HVR1 and HVR2).
Presence of Haplotypes is Important for Studies on Mitochondrial DNA in Human Migration
Tracing human migration by studying mtDNA is based on the observation of the presence of certain haplotypes often associated with certain regions of the world. Additionally, it also depends upon the assumption that the occurrence of such (mtDNA) haplotypes is a result of the accumulation of various mutations in different maternal lineages that occurred as people migrated and inhabited new regions.
The hotspot SNP (single nucleotide polymorphism) that occurs in the genetic code of the mtDNA D-loop region can be used to determine the maternal ancestry by haplogroup determination.
Fast Track>>> Haplogroup= a group of people that share a similar pattern of the SNPs in their DNA).
Fast Track>>> Single-nucleotide polymorphism = DNA sequence variation between the genome of the members of a species or a paired chromosome in an individual by virtue of the difference in a single nucleotide adenine (A) or thymine (T) or cytosine (C) or guanine (G). It occurs due to mutation. For example, AATCGG and AATCCG are two nucleotide sequences that exhibit SNP. There are two alleles, that is G and C.
Apart from mtDNA haplotypes, Y Chromosome DNA haplotypes also play an essential determining role in evolutionary genetics. It may be noted that a higher organism, for example, humans, receive the cytoplasm and organelles basically from the maternal ovum or egg cell. At the same time, the paternal side passes only the chromosomal DNA containing the Y chromosome.
The study revealed two migratory routes from Africa based on mtDNA sequences:
(i) mt Haplogroups L0 and L1-6, along with several other L-series haplogroups, suggests that the first human migrations took place out of Southern Africa.
(ii) The Southern Route represents the haplogroup M whose expansion can be delineated from Ethiopia through the Arabian Peninsula to India and Eastern Asia. The presence of M haplogroup derivatives along the route is due to a lack of back migration from Central Asia since the M diversity is higher in India than in Ethiopia.
(iii) The Northern Route gets separated into three main clusters. The first cluster consisting of the haplogroups W, I, and N1b are found in Europe, the Middle East, Caucasia, Egypt, and Arabian Peninsula.
The second cluster represents the haplogroup X and A found in Europe and Asia, respectively.
The third cluster is further subdivided into four lineages. The first lineage consists of haplotype B found in Japan, East Asia, and Southern Pacific. Archipelago, the second, ascended to the haplogroup J and T. The third lineage formed the H and V haplogroup, and U represents the fourth lineage whose sub-haplogroups has the highest frequencies in India (U2, U7); North Africa (U3, U6) and in Europe (U5).
(iv) The major European mtDNA lineages are U5, H, I, J, K, T, V, W, and X. The American haplogroups- A, B, C, and D have common origin indicated by their similar nucleotide polymorphism. The climate-induced adaptive selection also influenced the continent specific distribution of mtDNA lineages. It is indicated by the variability pattern of particular mtDNA sequences, such as the ATP6 gene (ATP synthase membrane subunit 6) from various temperature zones. ATP6 gene is essential for normal mitochondrial function.
Other Connections
The ATP6 protein forms a subunit of an abundant enzyme called ATP synthase. This enzyme, also known as complex V, is responsible for the final steps of oxidative phosphorylation. Several mtDNA haplotypes are suggested to involve in regulating oxidative phosphorylation, thereby influencing the physiological variation of susceptible to a particular disease.
Evidenced from various conditions like- Alzheimer’s and dementia with Lewy bodies, cardiomyopathy, and multiple sclerosis associated with specific mtDNA haplotypes further substantiate mtDNA as the favorable target to determine the underlying causes of certain human disease to the particular human race, evolutionary history, and their diversification.
Credits:
Featured Image: Mitochondrial DNA in Human Migration Study
mtDNA haplogroup tree and distribution map
Ph.D. Biotechnology, Manipur India
