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Modeling the Mitochondrial DNA "Clock" Underlying The Eve Hypothesis

Sandy Bornstein

The "Mitochondrial Eve" hypothesis derives from the discovery, made by Wilson, Cann, et al., of the remarkable similarity in mitochondrial DNA base sequences between all the thousand or so modern human blood samples that have been studied to date. By attempting to minimize the number of mutational steps theoretically needed to arrive at the present level of divergence between samples, a branching "family tree" of modern human populations has been established which requires only thirteen or fourteen separation events to account for the existing pattern (representing migration events in recent human history?).

The technique of mtDNA analysis has at its foundation assumptions about the steady accumulation of point mutations in "unselected" regions of mitochondrial DNA - assumptions that are not unchallenged in the scientific community, but which are necessary to understand in order to analyze the current debate. It is sometimes difficult to visualize in the abstract the impact on patterns of DNA sequences of point mutations that accumulate while populations of an evolving organism are simultaneously becoming reproductively isolated from one another. The activities that follow try to simulate such pattern changes based on accumulated random base mutations.

The activities start by producing a random sequence of thirty bases in a short chain of hypothetical mtDNA by pulling number tiles from a bucket and base tiles from the bag, almost like a game of BINGO. As each base tile is picked, assign that letter to the numbered position on the growing imaginary original mtDNA chain. After the original chain is established a series of mutations are imposed "randomly"; at every "step" in the process, one random point mutation occurs in these chains of mtDNA. The position and nature of the mutation will be determined by blind selection of the same BINGO-style tiles; a number tile is picked to determine the location of the change and a letter tile is picked to determine the base to which the position changes. Simultaneously, populations of mtDNA are sequentially "isolated" from the entire group. From the moment of their "divergence" these populations will accumulate their own sets of random point mutations at the same rate as all other populations, but independent of them. For each isolate a separate number and base tile is chosen.

At the end of the activity, "collect" all of the altered mtDNA sequences and analyze their patterns. The homework is to analyze how those altered base patterns relate to the sequence of divergence that produced them.

For more information:
Articles on the "Out of Africa" vs. "Multi-Regional Evolution" debate appeared in Scientific American in April, 1992 on pages 66 to 83.

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