There is a world of wonder inside us and its home is in almost every cell our body carries. ( Well, I say ‘almost’ because apart from your cells, there are more than 100 trillion microorganisms that live inside you?) It’s been over 60 years since the molecular structure of DNA was discovered, and the world still looks at the double helix with wonder.
This little molecule, present in millions in the body, with four letters (A,T,C,G aka nucleotides) repeated 3 billion times, can direct the constructions, operations, and terminations of almost everything your body is capable of doing. There actually is an amazing world inside our cells, and we, the geneticists, have set out to find all of its wonders. Alright, alright, I am not yet one. I am on my way to get my PhD; give me some time and it will be official!
Many of us geneticists study the functional information present in the genes: tiny fragments in the 3-billion nucleotide sequence which are read and translated into proteins, which do most of the work inside your cells. What I do, on the other hand, is a bit different.
Some mutations have a silver lining
Apart from genes, there are a lot of other sequences that do not code for proteins: they are called non-coding sequences, or also “junk” DNA, and that’s what I study. To be fair, nobody calls non-coding DNA “junk” nowadays, as scientists realized long ago the huge potential of studying these segments. So, what could I ever find in “junk” non-coding DNA?
First of all, let me introduce you one the many fields of people who study this allegedly useless DNA: we are population geneticists. Think about archeologists: they travel the world to dig the ground to find bones, pottery, and other remains to trace the stories of our ancestors. We dig in DNA instead. How?
Well, to answer that, we have to travel for a couple of thousands of years, but first, let me share with you two important concepts (for those of you who are eager to start traveling, you can skip them – see you in 10,000 BC!)
The first thing you have to know is that when we study the DNA we look for mutations – random errors that appear 1 out 1000 nucleotides when copying the DNA molecule: this is what makes you unique. Given that we have 3 billion nucleotides, and that mutations appear randomly, when we compare two (unrelated) genomes, we have at hand ~3 million differences to study (they are enough to discover cool stuff).
The more the two genomes are different in those 3 million sites, the longer it has been since they shared a common ancestor. For example, genetic differences between a snail and any human are higher than between an ape and a human, because the common ancestor is more recent between us and an ape. And we can apply this concept within species as well.
3 million differences and common ancestors
If a segment of your DNA is much more similar to the same segment of an 8000-year-old farmer from ancient Anatolia than one of a 4000-year-old horse-rider from the Steppe, this means that for that precise point (or locus) in your genome you are more closely related to someone who used to eat cereals under the shining sun.
So, the thing is that we can compare the 3 million nucleotides together, and find one great common ancestor between you and me, for example; or we can focus on several smaller sequences and find not one, but multiple points in time when we are closely related with different people (sometimes it may be from the Steppe, some other times from Anatolia), and so find the many different stories that we share.
You are a mosaic of your ancestors
And the second concept you need for this journey is that your DNA is made of fragments of the DNA sequences of both of your parents, which in turn inherited theirs from their parents and so on. So, when we go back deeper in time, the genome sequences now scattered all around your DNA can be found in your ancient ancestors (Due to how recombination works, one cannot have traces in their DNA of ALL his/her ancestors: after 8 generations just a small percentage of them contribute to his/her DNA).
Your DNA is not actually yours, it is all your ancestors together: you are a mosaic of all that has been before you. And that’s when the word “population” in population geneticists comes to hand: a whole-population history, a multitude of ancestors lay within your DNA. But modern contemporary genomes, due to recent admixture events, may not be able to tell us a clear and unclouded story, and thus, we must find a way look directly at the past.
We are almost ready to travel now – let me just show you the last ace up my sleeve before we start, which is the last great revolution in genetics: ancient DNA. Since 2009, when the first Neanderthal genome was sequenced, we had an avalanche of ancient DNA genomes: each of them give us a snapshot of the past and clues on how modern populations have been formed through time. With ancient DNA we can trace back all the pieces of the mosaic: relationships between old and modern populations can be drawn.
A letter from 7000 years ago
A common misconception about us is that we did not move. You look back at us, and you think, “With no cars, no planes, no trains, not even horses, how far could they ever go?” Well well, young boy, let me tell you the story of my grandpa. Born and raised in the far Anatolia around 7000 years before you, he has always been a hard worker.
Shortly after he was born, people in his tribe started to settle down, making their own home in a fixed place. I completely understand why my grandpa was excited about this: he and grandma finally stopped wondering around Anatolia to look for food and started to cultivate plants and milk goats in front of their mudded porch. The first American dream.
But don’t tell that to my wife! I met her here, in Central Europe, and her family had never understood mine. They still walk around, living, hunting, gathering and other stuff, so sometimes it’s a bit hard to decide how our kids should grow up. But, what do you want me to do? We are in love; we’ve got to make it work.
So, back to my grandpa. I guess that we, humans, are not a species you can make settle down for life. We are curious, we have legs and feet and not roots: we’ve gotta move. So grandpa and grandma, with others as well, started to travel to the west (I guess they got tired of the warm weather), and in the middle of this journey my mom was born.
Guess what? She wasn’t one to settle down either. As happened in the first generation, she started to travel west with others of the tribe, settling down when they could and bringing with them all the cattle they could. By an incredibly fortunate chance, she met my dad.
He, like my wife, lived life hunting and gathering and hardly stayed in one place for a long time. As far as I know, he was completely mesmerized with my mom: well, she was beautiful and exotic; I bet you’d fall for that even in 2019.
To make the story short, after a while I was born. I live in Central Europe now, the area of Germany for you future-people, and in my DNA I have two stories to tell: one of the people who used to inhabit this area for thousands of years (dad) and one of the people who arrived from Anatolia (mom).
But I’ll tell you something else, in the future (well, my future) my nieces and nephews will fall in love with even stranger people: they will arrive with horses from a faraway land called the Steppe, and so three stories will be told by their children’s DNA.
Their DNA, as yours, will carry traces of all the people before you: my dad’s and my wife’s, my grandpa’s and the Steppe people’s stories. And if we look closer at each of these, if we dig into every chapter of every story, we can go back for ages and tell many many more stories, thousands of them.
And all of them converge in you.
We all have incredible stories within our DNA, and studying them has been proven incredibly helpful. Since the advent of ancient DNA, we started to rethink our ancestors, their cultures, their ability to move and expand to other lands, their links with other communities: we, humans, have not changed that much.
And if you’re not an eager traveler, or your passions are more futuristic than mine (You’re allowed – I don’t judge), I’ll tell you this: many people have been misdiagnosed of certain diseases because many genome-wide association studies, in which geneticists look for any variant or mutations that could be associated with a trait or a disease, are based on analyses of people with a “European story” (European descent), and so the results are biased toward one ancestry. The stories within us are important, for our curiosity, but also for so much more.
1. Who We Are and How We Got Here by David Reich, 2018, Oxford University Press
2. Haak W. et al., “Massive migration from the steppe was a source for Indo-European languages in Europe”, 2015, Nature
3. Martin R. A., “Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations”, 2017, AJHG.
Ludovica Molinaro is a first-year PhD student at the Institute of Molecular and Cell Biology, and she works at the Estonian BioCentre with the modern population genetics group. She studies different populations and cultures while also trying to develop new methods to dig into our past.