Would someone from the time of Jesus Christ or Alexander the Great have noticeable genetic differences (from modern humans) to the trained eye? If not, how far back in human history would you have to go before a geneticist would spot those differences?

-A high school student from Alberta Canada

July 3, 2012

Your question is an interesting one.  And not easy to answer!

First off, people from thousands of years ago wouldn’t look too different from modern humans.  Give them the right clothes and teach them a modern language and they would blend right in. 

But even though they’d look human, there would be subtle differences in their DNA that might give them away.  They would be missing some modern DNA differences and/or have some ancient ones that have been lost over time.   

In fact, that is what scientists saw when they recently looked at a 4,000 year old man’s DNA.  They had to do a lot of work to distinguish this ancient DNA from that of modern Inuits. 

The differences between a modern Macedonian and Alexander the Great would be very subtle.  To really see big differences, you’d need to go back 150,000 or 200,000 years ago.  This is when Homo sapiens first evolved.  Anyone’s DNA from before then would undoubtedly look different.  And they’d look different from us too!

See I told you this was hard to answer!  What makes it so hard is that DNA changes gradually over time.  And that it gets mixed and matched every generation. This makes it very hard to pinpoint a time when the DNA was noticeably different between modern and ancient humans.

What I thought I’d do for the rest of the answer is talk about how our DNA changes over time.  As you’ll see, we all have a few unique genetic differences that neither parent gave us.

DNA Changes Over Time

Your genetic information is stored in your DNA sequence.  It has all the instructions for making and running you.

These instructions are written with four bases called adenine, thymine, cytosine, and guanine.  To make things simpler, scientists refer to them by their first letter: A, T, C and G.  It is like a very simple alphabet made of four letters.

You have a unique string of 6 billion or so of these four letters that has the instructions for making you.  And I have a string of 6 billion or so of As, Gs, Cs, and Ts that has the instructions for making me.   On average, we have a different base every thousand letters or so.

Alexander the Great would have a very similar string of 6 billion letters.  And he probably wouldn’t have too many more differences than you and I have. 

What would be different is that he might have a few changes that no one alive today has.  And he might be missing a few common ones that most of us share.

These differences arise from changes in our DNA called mutations.  This is why you have a few DNA differences that neither parent gave you.  They are uniquely yours.

Everyone is a Mutant

A mutation is just a change in the DNA.  They are very common, usually have no effect, and where they happen is totally random.

Sometimes mutations are as simple as changing one base.  For example, an A could be changed to a G.  Sometimes bigger sections, even up to thousands of bases, can be added, deleted, or even duplicated. 

These kinds of mutations can happen from damage by chemicals or certain kinds of radiation, but a lot of the time they are simply mistakes.  See, when cells divide they have to copy their DNA and they don’t always make a perfect copy.  In fact, they never do.  They always make mistakes. 

These mistakes tend to happen at a pretty constant rate.  This means you can tell how far apart in time two samples are by how many unique mistakes each has. 

Imagine you are copying a book and you make five mistakes every time you copy the book.  If you compare two copies of the book and you find 25 changes between the two, then how many times has the book been copied?  You’re right, five times. 

Scientists call the rate of mutations the molecular clock and they use it to see how many generations have passed between two DNA samples.  The more changes you have, the less related the samples are.  

This is how scientists would be able to tell that Alexander the Great’s DNA was from thousands of years ago.  But they can only tell if they have a lot of modern DNA to compare it to.

Migrations and Mutations

As we discussed above, humans first evolved in Africa 150,000 to 200,000 years ago.  Then, about 70,000 years ago, a group of people migrated out of Africa and began living in the Middle East. 

Over time, more groups split off from this Middle Eastern group and migrated to live in Europe and Asia.  More groups then split off from these European and Asian groups over time so that eventually there were humans living all over the world!

But traveling long distances was hard thousands of years ago.  People didn’t have cars and airplanes and trains to use to get places, so once a group of people migrated away they would be separated from all the other people on earth. 

Over the generations, mutations would build up in these people and their children, and these mutations would be different from the mutations that other people in the world might have.  The mutations of people from one part of the world form a certain pattern that is different from the pattern of mutations of someone from another part of the world.

Let’s go back to our example of copying a book but this time, we’ll think about copying just one sentence.  As you can see below, each time a sentence is copied, we make a single mistake:

For example, the first time we copy the sentence, the y in yam is changed to an h.  This change is like a mutation.  So, if this were DNA, our mutation rate would be one per generation. 

Then, after our third copy, or generation, a group breaks off (like a group of humans migrating to a new place).  Now there are two groups, and mistakes (mutations) happen in each of these groups. 

The changes they have in common that happened before the migration are in red (sentences 1-3).  But the new changes for the group on the left are in blue (sentences 5a and 6a), and the new changes for the group on the right are in green (sentences 5b and 6b). 

If you were to compare sentences 1, 6a, and 6b, you would see that there are 4 changes each between 6a and 1 and 6b and 1.  Remember that our molecular clock for this type of change tells us that we should get one mistake per time the sentence is copied (per generation). This means there have been 4 copies made between sentence 6 (a and b) and sentence one. 

But there are only two changes that 6a and 6b have in common (the red ones) and two that are unique to each (the blue and green changes).  This way we know that the group a split off from group b 2 copies ago. 

Scientists can do the same thing with mutations in DNA that we did with our sentences to determine what group of modern humans an ancient sample is most related to and how many generations have passed between the sample and modern humans. 

If you had the DNA sequence of Alexander the Great, you could use the pattern of mutations to determine what group of modern humans he is most related to.  Then you could use the number of changes between his DNA and the most closely related modern DNA to determine the number of generations that have passed since his life. 

So there you have it.  The DNA differences between a modern Macedonian and Alexander the Great would be subtle but a trained scientist could, with a little work, see them.

For the last several hundred years people have been moving all over the world and having children with people whose ancestors come from different places.  In the United States (and Canada), unless your family is Native American, we are all immigrants from somewhere else.  Scientists can use the pattern of mutations in a person’s DNA to determine where in the world their ancestors came from. 

Scientists are hard at work sequencing the DNA of people from all over the world to make a better and better map of when humans first migrated to new places, where they migrated from, and what they might have looked like.

By Katie Sharp, Stanford University

It would take a trained eye to tell Alexander the Great's DNA from modern Macedonians.

DNA mutations are so common you defintely have afew that neither your mother nor father has.

Using mutations we can trace human migration through history.