Tuesday, July 17, 2007

Mitochondrial DNA and Human Evolution

"Where do we come from?" This has been one of the fundamental questions asked by humans for thousands of years. Is it philosophical? Religious? Anthropological? Depending on your view point it determines how you look for the answer. From an anthropolical viewpoint physical anthropologists have been looking for answers by studying morphological characteristics of bones or skeletons that have been uncovered, such as skull shape, of the fossilised remains of our human and proto-human ancestors.

Molecular Anthropology - New study
Molecular anthropologists have been comparing the DNA of living humans of diverse origins to build evolutionary trees. Because mutations occur in our DNA at a regular rate and will often be passed along to our children these differences or polymorphisms, as they are termed, show that on a genotypical level make us all unique and analysis of these differences will show how closely we are related. But using these techniques, however, have led to opposing views on how modern humans evolved from our archaic ancestors.

Two competing theories

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
This theory suggests that modern humans evolved from archaic forms, such as Neanderthal and Homo erectus. They originated concurrently in different regions of the world supported by physical evidence, such as the continuation of morphological characteristics between archaic and modern humans. But this is the minority view.

2) Out of Africa view
This view holds that modern humans evolved in Africa before colonizing the world. The recent African origin view holds that modern humans evolved once in Africa between 100 - 200 thousand years ago. Subsequently modern humans colonised the rest of the world without genetic mixing with archaic forms supported by the majority of genetic evidence. This is now the majority view.

Which theory is right?

One way to answer this is by looking at mitochondrial DNA. While DNA is present inside the nucleus of every cell of our body it is the DNA of the cell's mitochondria that has been most commonly used to construct evolutionary trees.

What is Mitochondrial DNA?
This is DNA found outside of the cell nucleus. They are inherited only from the mother, which allows tracing of a direct genetic line. They also have their own genome of about 16,500 bp. Each contains 13 protein coding genes, 22 tRNAs and 2 rRNAs. Fewer samples is required vecause they are present in large numbers in each cell. And they have a higher rate of substitution that is mutations where one nucleotide is replaced with another than nuclear DNA making it easier to resolve differences between closely related individuals. They don't recombine. Mitochnondrial DNA doesn't recombine with other Mitochondrial DNA. The process of recombination which occurs in nuclear DNA mixes sections of DNA from the mother and the father creating a strained genetic history.

So Mitochondrial DNA tells us what?
The out of Africa theory has support from Mitochondrial DNA. But these conclusions have been criticised for a lack of statistical support. This is due to the fact that a small section of the Mitochondrial DNA called the D-loop, about 7% of the genome has been used for the studies. Statistically, the out of Africa theory is not well founded. Here is why. 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.
But there has been a study that has fixed some of these problems. First the mitochondrial genome is one of the first genomes to be sequenced in its entirety. However it was not until recently that technological advances allowed large sequences to be obtained easily and a study of any appreciable size using whole genomes was undertaken. There were some clear advantages.

First the D-loop was evolving at a much higher rate. And this 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). Second the numbers of back- and parallel mutations found outside of the D-loop were practically zero. So this had no effect. And finally the rate of evolution of the rest of the genome was even between different genes and also between the different gene complexes; it was also even between different sites

The phylogenetic tree reconstructed with this latest dataset of complete mitochondrial genomes provides support to the 'recent African origin' theory. Chronologically speaking 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.' That date about 171,500 years ago fits very well with that proposed in the recent African origin hypothesis.

On the other hand, in order to accept multi-regionality, a much older date would have had to be used; this would represent the common ancestor of Homo erectus and not Homo sapiens.

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