Genetic diversity and our ancestors

Published in the MDI Islander Friday, October 10, 2008.

What would you think if a perfect stranger walked up to you in the street and asked: "How’s it goin,’ cousin?"

Senator Barack Obama and Vice President Dick Cheney were revealed to be eighth cousins on Obama’s mother’s side. Aside from sharing a gene for public service, their kinship is meaningless. Isn’t it?

You might rightly think it an odd thing to say, but you’d be wrong to deny it. All humans have a single common ancestor, and so each and every one of us is indeed a cousin.

But, at such a distance, do we care? Recall in the past year when Senator Barack Obama and Vice President Dick Cheney were revealed to be eighth cousins on Obama’s mother’s side. Aside from sharing a gene for public service, their kinship is meaningless. Isn’t it?

Not quite. The puzzlement only reveals how we are much more attuned to cultural values than to genetic connections. Genetically, or at least genealogically, we are much more closely related to each another than we realize.

Eighth cousins share a pair of great-times-seven grandparents. So, around 225 years ago, or nine generations, Senator Obama and Mr. Cheney’s most recent common ancestor was born. Isn’t it odd to think that the period corresponding to all of our venerable American history is barely the blink of an eye in genetic terms? At Jackson Lab, we can breed nine generations of mice in little over a year. If you could show just one meaningful genetic difference that arose during this period, you would have a rather unique scientific paper!

So, where does human genetic diversity come from? While new mutations crop up at a low rate each generation, most diversity comes from pre-existing "old" variants that accumulated and mixed-in with both new and old ones in every generation. An obvious, albeit superficial difference between Sen. Obama and Mr. Cheney - skin color - happens to be an example of this "old" variation: some of both men’s ancestors left Africa permanently around 30,000 years ago, or 1,500 generations, and evolved genes for lighter pigmentation as they adapted to new climates. Sen. Obama’s paternal ancestors probably hung around longer, retaining their pigmentation.

Still, even 100 generations is not a lot of time for genetic differences to dominate a species. In mice, we usually have to look back over 8 million mousey generations (~1 Myr) before genetics make a critical difference - the ability of matings to produce fertile offspring. Now that’s something that matters.

As it turns out, it’s not such a surprise that Sen. Obama and Mr. Cheney are related. Amazingly, a most recent common ancestor for all of us probably lived only around 120 generations ago, in the first few millennia BC. In his engaging book, "Mapping Human History," Steve Olson suggests that, if you time-traveled back this far, most every ancestor you meet would be your own, and these would be everyone else’s ancestors as well!

Simple math shows that you had lots and lots of ancestors then: they double with each regressing generation - two parents, four grandparents, eight great-grandparents, etc. Although the actual number of your ancestors in, say, 1000 BC is reduced by non-random marriages (e.g., between cousins) and other factors, it’s still in the millions. Mr. Olson even notes that most of us are probably descended from prolific historical figures, as long as they had grandchildren. So, you can go to your encyclopedia and pick and choose which ancient masters you’d like to have been descended from. Because chances are, you were!

Okay, so, if we share recent ancestors, why do we differ so much in appearance and susceptibility to diseases such as heart disease, cancer, Alzheimer’s, etc? It’s probably because much diversity is of the "old" variety. Considering that we had so many ancestors in ancient times, with each and every one potentially contributing to our make-up, it’s obvious how old mutations persisted: there were simply so many opportunities to inherit them! But in actuality, not every direct ancestor contributed: as Olson also points out, you have to go back only six generations to reach a point where one of your 64 great-great-great-great grandparents may have had little or no genetic contribution to you. So, even when we share ancestors, we inherit different bits of their genomes.

Several research initiatives are focused on examining old and new diversity to understand the genetic basis of disease. There is major push to solve genetically complex diseases - those caused by multiple variants inherited in the wrong combination - because they are far more common than simple genetic diseases. The way forward is to map our ancestors’ contributions to our respective genomes, and to compare and contrast, matching-up the shared guilty variants with disease. To do this right, we need each other. Any other way would just be guessing.

It is a challenging time, because while it is inevitable that this needs to be done, it also means that we will be genetically fingerprinted, raising issues about privacy and discrimination. Might not be a bad time to get into the legal profession.

Bar Harbor resident and Jackson Laboratory Professor Wayne Frankel, Ph.D., studies the mechanisms of brain diseases, including inherited epilepsy.  Dr. Frankel welcomes your feedback on his column.

More articles by Dr. Frankel

Subscribe to JAX eNews

Our monthly newsletter highlights the latest happenings at the Lab.