More Things in DNA, Horatio …

From: Our Human Variability

Biology fascinates me. But as a non-expert, I’m forced to think of things in pretty simple terms. So when I hear biologists talk about evolution, adaptability and natural selection, I always find myself asking: What’s going on, exactly? What are the physical mechanisms at play?

After all, if a species evolves through mutations of its members, then these mutations must be physically represented somewhere. And where else could that happen other than in our DNA, our own personal “instruction manual” of nucleotides and genes that we carry with us in every cell.

If evolution is as strong a force as we are led to believe, then, these sorts of variations must somehow be happening all around us, resulting in a world replete with manifold diversity and uniqueness that is layered upon our common humanity. Which is — to all intents and purposes — pretty well what we see when we look around and see such differences in the people on all sides of us. So far, so comprehensible.

But when The Human Genome Project announced that their DNA sequencing experiment demonstrated that we were all “99.9% identical”, things took a decided turn towards the unintelligible for me, and my first reaction was one of sceptical confusion, rapidly followed by one of embarrassed withdrawal.

Like many laymen, the conclusions seemed downright perplexing to me, but who on earth was I to question the scientific consensus of thousands of expert researchers from around the world?

Stephen Scherer, on the other hand, a world-class geneticist who built an internationally renowned research program at Toronto’s Hospital for Sick Children, naturally felt less inclined to be deferential to the prevailing wisdom.

Howard Burton in conversation with Stephen Scherer, University of Toronto

Let’s run the numbers. For a human genome of roughly 3 billion nucleotides, that 0.1% difference results in variations of about 3.2 million of the individual nucleotides that make up the “human genome”. So that’s one way to look at things.

But, crucially, it’s not the only way.

Many years before the Human Genome Project reached its conclusion, geneticists had also recognized that some 0.4% of the population exhibited large-scale deviations from the norm — so-called “copy number variation” — where huge chunks of DNA, often millions of nucleotides long, were either missing from their genome or present in extra copies. All of these large-scale changes were associated with serious medical conditions like autism or Down syndrome.

There were, then, it seemed two types of variation: one for the “diseased” and one for “the rest of us”. It was a picture that most geneticists and molecular biologists of the time unhesitatingly accepted. But not Stephen.

He didn’t develop the right tools himself. But as a self-confessed “technology guy”, Stephen had the presence of mind to aggressively seek out better and different techniques to see what others might have missed.

In 2003, he partnered with Craig Venter’s Celera Genomics to study the DNA of chromosome 7, his primary area of expertise. Venter had pioneered a different sort of DNA sequencing technique, called “shotgun cloning”, that had also been used for the Human Genome Project. Now there was a way of comparing and contrasting the two approaches.

So “copy number variation” again, but this time not necessarily associated with any particular condition or disease. What Stephen and his colleagues had stumbled upon was the groundbreaking possibility that large-scale, DNA copy-number variation might be nothing less than a universal human trait, a key ingredient in allowing evolutionary variability — concrete evidence, in other words, that we were far more distinctive than the Human Genome Project was telling us we were.

More work, though, needed to be done — and, once again, with cutting-edge tools.

Ten times as much variation? How, then, is it possible that so many others could have missed it? How could The Human Genome Project — one of the largest and most comprehensive scientific collaborations in human history — have overlooked such a humongous elephant in the room?

For rigorously following his sceptical hunches, Stephen now firmly occupies a place in the pantheon of the scientific establishment. But however large the personal accolades become, they are dwarfed by the fundamental change in our understanding that his research has brought, not only the extent of our genetic individuality, but also — even more importantly still — of appreciating what it means to be human.

Howard Burton,

This is the introduction of the book called Our Human Variability. This thought-provoking book is based on an in-depth, filmed conversation between Howard Burton and Stephen Scherer, the GlaxoSmithKline Research Chair in Genome Sciences at the Hospital for Sick Children and University of Toronto.

The book is broken into chapters and includes questions for discussion at the end of each chapter. Visit the page for Stephen Scherer for further details about the book and videos developed from the filmed conversation: and watch a clip here:

This book is also available as part of the 5-part Ideas Roadshow Collection called Conversations About Biology, also featuring Nick Lane, Frans de Waal, Mattew Walker and Alcino Silva.

Visit our website for further details:



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