Mitochondrial DNA Clarifies Human
Evolution By Max Ingman
Mutations in human DNA
are used to show relationships and evolutionary
history.
"Where do we come from?" This has been
one of the fundamental questions asked by humans
for thousands of years. Physical anthropologists
have been providing an answer for over a hundred
years by studying morphological characteristics,
such as skull shape, of the fossilised remains of
our human and proto-human ancestors.
For
the last 15 years or so, molecular anthropologists
have been comparing the DNA of living humans of
diverse origins to build evolutionary trees.
Mutations occur in our DNA at a regular rate and
will often be passed along to our children. It is
these differences (polymorphisms) that, on a
genotypic level, make us all unique and analysis
of these differences will show how closely we are
related. However, different approaches used by
molecular and physical anthropologists have led to
opposing views on how modern humans evolved from
our archaic ancestors.
Multiregional view:
modern humans evolved from earlier hominids in
different parts of the
world.
Two main hypotheses
The
two main hypotheses agree that Homo erectus
evolved in Africa and spread to the rest of the
world around 1 - 2 million years ago; it is
regarding our more recent history where they
disagree.
1) Multi-regional
evolution
suggests that modern humans evolved from
archaic forms (such as Neanderthal and Homo
erectus) concurrently in different regions
of the world
supported by physical evidence, such as
the continuation of morphological
characteristics between archaic and modern
humans
now a minority standpoint
Out of Africa view:
modern humans evolved in Africa before colonizing
the world.
2) Recent African origin
proposes that modern humans evolved once
in Africa between 100 - 200 thousand years
ago
modern humans subsequently colonised the
rest of the world without genetic mixing with
archaic forms
supported by the majority of genetic
evidence
Mitochondrial DNA --
maternal DNA -- is used to construct evolutionary
trees.
Mitochondrial DNA
DNA is
present inside the nucleus of every cell of our
body but it is the DNA of the cell's mitochondria
that has been most commonly used to construct
evolutionary trees.
Mitochondria have their own genome of
about 16,500 bp that exists outside of the cell
nucleus. Each contains 13 protein coding genes,
22 tRNAs and 2 rRNAs.
They are present in large numbers in each
cell, so fewer samples is required.
They have a higher rate of substitution
(mutations where one nucleotide is replaced with
another) than nuclear DNA making it easier to
resolve differences between closely related
individuals.
They are inherited only from the mother,
which allows tracing of a direct genetic
line.
They don't recombine. The process of
recombination in nuclear DNA (except the Y
chromosome) mixes sections of DNA from the
mother and the father creating a garbled genetic
history.
Mitochondrial DNA
displays high mutation rates.
Focussing on the
D-loop
Evidence from DNA studies
generally supports a recent African origin but
these conclusions have been criticised for a lack
of statistical support. One possible reason for
this is because these studies have focussed mainly
on the polymorphisms in a small section of the
mitochondrial genome called the D-loop, which
comprises around 7% of the mitochondrial genome.
The reason for this section's popularity lies in
its particularly high mutation rate, meaning that
scientists can analyse this relatively short
sequence and still resolve differences between
closely related sequences. Unfortunately, it is
now becoming increasingly clear that this very
high mutation rate is actually obscuring the
informative information. Three main problems with
data from the D-loop section have been
identified:
back mutation - sites that have already
undergone substitution are returned to their
original state
parallel substitution - mutations occur
at the same site in independent lineages
rate heterogeneity - there is a large
difference in the rate at which some sites
undergo mutation when compared to other sites in
the same region; data shows evidence of 'hot
spots' for mutation
Now that the entire
genome can be sequenced, we should get a clearer
picture of the origins of modern
humans.
A solution?
Although the
mitochondrial genome is one of the first genomes
to be sequenced in its entirety, it was not until
recently that the progression of technology
allowed sequences of that length to be obtained
with relative ease and a study of any appreciable
size using whole genomes was undertaken. This
study became an important landmark in the field of
population genetics and perhaps will be a
precedent for a new field, already coined
"population genomics." These researchers (Ingman
et al., see references) found that although
sequencing the whole genome was considerably more
work, it provided some important
advantages.
Although the D-loop was evolving at a
much higher rate, the greater length of the
complete genome allowed for the analysis of
twice as many informative polymorphic sites
(sites that show the same polymorphism in at
least two sequences).
The numbers of back- and parallel
mutations found outside of the D-loop were
practically zero.
The rate of evolution of the rest of the
genome was surprisingly even between different
sites, different genes and also between the
different gene complexes.
A new study shows that
modern humans appeared 171,500 years ago in
Africa.
Population genomics
The
robust phylogenetic tree reconstructed with this
dataset of complete mitochondrial genomes gives
strong support to the 'recent African origin'
theory. By determining the substitution rate of
the genomic sequences, it is possible to derive
dates for points on the tree and build a
chronology of events in the evolution and
migration of our species.
The most important date, in relation to
the competing evolutionary theories, is the time
when all the sequences coalesce into one -- the
'mitochondrial Eve.'
From this study, a date of 171,500 years
ago was obtained which fits remarkably well with
that proposed in the recent African origin
hypothesis.
For us to accept multi-regionality, we
would expect a much older date, as it would
represent the common ancestor of Homo
erectus rather than of Homo
sapiens.
The evolutionary
history of aboriginal populations still remains a
mystery.
This study is only the first and population
genomics is in its infancy. The future will
provide more studies with ever-increasing numbers
of sequences from yet unanalysed populations and
perhaps an interface between genetic data from
different loci. For example, a recent study of
ancient human remains in Australia integrated
genetic data with the information collected by
physical anthropology. There are many important
questions that remain to be resolved such as how
and when the Aborigines arrived in Australia and
the evolutionary history and relationships of
North and South American Indians.
About the author: Max Ingman, an Australian, is
completing his doctoral degree in medical genetics
at Uppsala University, Sweden. Recently, he and
his colleagues analysed the complete mitochondrial
genomes of people selected from diverse
geographical, racial, and linguistic backgrounds.
It is considered to be the most thorough analysis
to date. He continues to work on projects that
deal with the evolutionary histories of certain,
somewhat enigmatic, populations. http://www.uu.se/findperson.php?uid=N99-1523
Human origins:
paleoanthropology The human origins program
at the Smithsonian Institution. A site intended to
educate about human origins through the field of
paleoanthropology. http://www.mnh.si.edu/anthro/humanorigins/
Human origins: archaeology An
archaeology information site with details on the
different forms of archaic humans and discussions
on relevant topics. Provides a good list of links
to more information on anthropology. http://www.archaeologyinfo.com/index.html
Human origins:
genetics University College London, Centre
for Genetic Anthropology site with information on
the use of Y-chromosome data in the study of human
evolution. Includes a 'Beginners background' page
on genetic (molecular) anthropology. http://www.ucl.ac.uk/tcga/
Fossil evidence in 3D This
gallery contains five modern primate crania and
five fossil crania which can be rotated 360°. Each
cranium is accompanied by a short description of
its relevance to human evolution. http://www.anth.ucsb.edu/projects/human/
The United Mitochondrial Disease
Foundation This site provides information and
support to those who are affected by mitochondrial
diseases -- hereditary disorders, now considered as
common as childhood cancers, that affect the cell's
ability to produce life-sustaining energy. http://www.umdf.org/
» Wilson, A.C. and Cann, R.L. "The
recent African genesis of humans." Scientific
American 266 (4) 68-73 (1992). »
Thorne, A. G. Wolpoff, M. H. "The multiregional
evolution of humans." Scientific American
266 (4) 76-9, 82-3 (1992). » Wills, C.
Children of Prometheus: The Accelerating Pace
of Human Evolution. (Perseus Books, Reading,
MA, 1998). » Max Ingman, Henrick
Kaessmann, Svante Pääbo, Ulf Gyllensten.
"Mitochondrial genome variation and the origin of
modern humans." Nature 408, 708-713 (Dec.
2000). » Cavalli-Sforza, L.L. Genes,
Peoples, and Languages. (New York. North Point
Press, 2000).
ActionBioscience.org original
lesson This lesson has been written by a
science educator to specifically accompany the
above article. It includes article content and
extension questions, as well as activity handouts
for different grade levels.
Lesson
Title:mtDNA: So What Did
You Inherit from Your Mom? Levels:
high school - undergraduate Summary:
This lesson examines the structure and function
of mitochondria. Students can produce a page for
an organelle catalog, conduct a mock radio
interview, assess myths about Mitochondrial Eve…
and more! Download/view
lesson, click icon: (To open the lesson's PDF file, you
need Adobe Acrobat Reader free
software.)
Useful links for educators »
Mitochondrial Control Region A how-to
library which allows high school and college
classes to isolate mtDNA, and to have it processed
free of charge at the Cold Spring Harbor
Laboratory. Click on "sequencing service." http://www.geneticorigins.org/geneticorigins/mito/mitoframeset.htm
