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Mitochondrial DNA
M.Tevfik Dorak, M.D., Ph.D.
Mitochondrial DNA (mtDNA)
of higher animals is a circular molecule of some 16,000 bases. It corresponds
to chloroplastic DNA of plants both of which are collectively known as
cytoplasmic DNA. The mtDNA has no repetitive DNA, spacers, or introns. It
encodes 13 mRNAs, 22 tRNAs and 2 rRNAs. mtDNA is usually the only type of DNA
to survive in ancient bone specimens because of its abundance; 500-1000 copies
per cell instead of only two copies of most nuclear DNA. Unlike nuclear DNA
which gets mixed around each generation (this is each meiosis), the only
alteration to mtDNA is an accidental change caused by mutation, copying errors,
or other accidents, i.e., it does not recombine. mtDNA is maternally inherited.
All the copies in an individual are usually identical but populations may be highly
polymorphic. The lack of polymorphism within individuals suggests that at some
point in the germ-line, the effective number of copies must have been small.
The rate of base
substitution in mtDNA is much higher than nuclear DNA. An estimate of the initial
rate of sequence divergence is 20x10-9
per site per year per evolutionary line (this is 2% sequence divergence per
million years between pairs of lineages; 10 times faster than the highest rates
in nuclear DNA). This estimate applies only to the first 10 million years of
species separation after which mtDNA sequence divergence begins to plateau as
many bases are conserved and the genome becomes saturated with substitutions at
variable sites. This high rate of substitution makes mtDNA particularly
valuable in studying the relationships in recently diverged lineages.
The fact that the mtDNA
is inherited only through the female line without crossing-over provides unique
information to phylogenetic studies as it preserves information about ancestry.
The only source of sequence variation is mutation at a well-worked out
stochastically constant rate so that divergence times (coalescence times) can
be estimated.
Among human populations,
restriction maps of mtDNA reveal rather little sign of geographical
structuring. This suggests that existing human populations migrated from a
common center relatively recently. Based on the divergence rate of 20x10-9, the mean time of divergence of human races is of the
order of 50,000 years. mtDNA data have also been used to estimate effective
population size (Ne; those contributing to the next generation) in
the past. The total divergence time elapsed since a single ancestral sequence
(coalescent) gave rise to today’s variants is 4xNe generations
(time for a neutral mutation to get fixed). mtDNA is haploid and maternally
inherited; hence, the mean coalescence is 2xNf, where Nf
is the number of mothers. When the total divergence is estimated within the
existing human populations, based on the sequence divergence rate of 20x10-9 per year, it has been concluded that the single
common ancestor for all the variant sequences in today’s human
populations existed 10 to 20 thousand generations ago (200 to 400 thousand
years, assuming 20 years as generation time). This means that Nf
must have been about 5 to 10 thousand.
It is important to
understand the claim that all existing human mitochondria are probably derived
from a single female living less than half a million years ago does not mean
that our ancestral lineage was ever reduced to a single pair or that only one
female contributed to our nuclear genome. Surely most of the females within the
effective population at the time contributed to our nuclear genome but the
female all our mtDNAs trace back lived 200 to 400 thousand years ago. More
technically, the extant mtDNA alleles coalesce to a single ancestral molecule
extant at that time. It is a mathematical certainty that each gene will
coalesce into one ancestor, the others just have not been able to make it today
(similar to the extinction of surnames). Each one of our 40,000 genes can be
traced back to its own ancestral gene. It is important to remember that only
those females who have daughters have the chance to pass on their mtDNA to
following generations. A similar calculation has been made for HLA-DRB1 genes.
All extant DRB1 alleles seem to have derived from one ancestor lived more than
65 million years ago.
One study compared a long
stretch of mtDNA in humans in different primate species. This study (Horai,
1992) showed that humans are closer to chimpanzee than gorillas in terms of
their mtDNA genealogy. When the divergence of mtDNA is compared among
populations, the initial mtDNA split was found between Africans and others,
followed by progressively younger calibrated ages for specific Asian,
Australian, New Guinea, European, and native American mtDNA types. This pattern
has been thought to support the Out of Africa model in the origin of modern
humans. This estimate is based on the concept that greater sequence variation
in mtDNA on a continent is a sign of greater longevity. African populations are
the oldest because they harbor the greatest mtDNA variation.
M.Tevfik Dorak, M.D., Ph.D.
Last edited on 9 January 2006
Evolution Genetics Population
Genetics HLA MHC Inf &
Imm Genetic
Epidemiology Epidemiology Glossary Homepage