I'm David Haussler, scientific director
of the UC Santa Cruz Genomics Institute,
and Howard Hughes Medical Institute investigator.
It's my pleasure to be able to speak to you
on the great questions in biology.
I want to have you imagine
that you just got your genome sequenced.
Now, when we sequenced the first genome
in the year 2000, it cost about $300 million,
just for the sequencing reagents and activities.
But nowadays, it's a couple thousand bucks.
So let's assume, you went out and got your sequence done.
Now looking at that, it may be hard to interpret
but it's got to be a moving experience,
to look at that DNA sequence and think about
how it got there.
In particular the DNA in your genome
was passed on from generation to generation
for eons.
We all come out of the primordial ooze somewhere
billions of years ago
And it's stunning to think that a record
of many of those evolutionary events
is still present in the genomes today.
So what would you do? What would you look a
to start to understand where you came from?
And what is specifically interesting about your genome
versus all the other genomes on the planet?
Probably the first thing you would think about
in terms of the way that DNA is inherited
from parent to offspring is:
are there any new elements of your genome
that weren't even in your parents?
And statistics say there will be a few
So there will be a few changes in the way the DNA
was copied. You could think of them as errors,
but you could also think of them as fortuitous events
that caused something different in your genome
that wasn't in either of your parent's genome.
Those would be interesting, certainly.
And there are probably only a very small handful of those.
The next thing you would think about is
is there something I inherited from my parents
that's just specific to my family in some sense?
Maybe it's something special that happened in
a great grandparent and has been passed down
to me through all of these generations.
Now this is the very stuff of genetics.
To think about this, in particular, medical genetics
you would be very concerned if this actually
made you prone to a disease
You might also be protected from a disease
by a special version of a gene that's in your genome
that's specific, or private, to your specific family.
That would be exciting.
And as we start to get the era from just one genome
in the year 2000, to the coming era of millions of genomes,
we will be able to, by comparing genomes,
understand what's specific to certain families,
what's specific to certain ethnic groups,
what's specific to humans in general, but not
with other species.
It's an enormous computational problem
to compare all of these genomes, and this is probably
the most significant challenge facing the computational part
of genetics and genomics today.
If you understood what was specific to humans
that would be fascinating, you could start to think about
what happened since we diverged from our common ancestor
with our closest species, the neanderthal.
While the neanderthals are extinct,
we were able to sequence DNA from their bones
and hence, get an idea of their genomes looked like.
And we find that there are more than a million changes
that occurred in the human lineage
since we diverged from our common ancestor
to neanderthal.
What an exciting project at this point, to try to understand
those changes that almost everybody
almost all of humankind share,
as opposed to and distinguish them from the neanderthal.
Going back further, about 5-6 million years ago,
we shared a common ancestor with the chimpanzee
Since that time, there have been roughly 15 million changes
in our genome.
Which ones actually account for the difference
between a human and a chimp?
This is a substantial difference
and remarkably, we still know very little
about which of those changes actually make that huge difference
between a human and a chimp.
One thing that you'll run into, in this quest,
is the fact that most of these changes
are probably not important
in some sense.
If you look at the structure of your DNA
and in particular, if you look at it from this perspective
of going back and looking at where the DNA came from
what it's history is,
you see that there are some parts of your genome
that are shared with virtually all other life
on the planet.
The genes and the DNA in the genes
and the ribosome sequences,
DNA polymerase. Other fundamental molecules
that make life itself possible
are remarkably little changed
over the eons of evolutionary time.
And so when you look at one of those bases in your genome
you can sit back and say, "wow, that's a really ancient base!"
"That base of DNA was passed on to me
all the way back from the beginning
billions of years, copied faithfully
again and again and again.
And now it is a gift to me
so that my cells work."
In between that are all stages of evolutionary innovation.
So when you look at your genome
you'll find genes that were created essentially
as an evolutionary process in the bilaterian animals,
for example.
The set of animals that have bilateral symmetry
is a huge collection of animals on the planet
that they didn't exist 2 billion years ago.
So all of their genetic innovations happened
after that period.
If you look at vertebrates,
animals with a backbone,
they didn't exist 800 million years ago, but now
we can find all of the different innovations
that are specific to the vertebrates,
the backboned animals, that don't exist in other animals.
And each one of these beautiful genetic variations
happened at a particular time
in the marvelous history of life.
So when you're looking at every gene in your genome,
you can say "Aha! That's a bilaterian innovation."
"Oh, and this one was invented by vertebrates."
"And maybe this one was invented by primates."
"And maybe this one is specific to apes."
Understanding this, is probably the greatest challenge
to genomics, going forward at this point.
And we have an extraordinary opportunity
to look at every base in the genome
for the first time.
And more importantly, to compare it
to the bases in other genomes.
The lesson we've learned from first sequencing the human genome
in the year 2000, and subsequently looking
at the first chimpanzee genome,
the first mouse genome,
the first rat genome,
the first dog genome,
is that no genome is ever understandable
in isolation.
Every time we sequence the genome of a new species
we learn more about the genomes that we had previously
sequenced from other species.
And that is precisely because
we share a common heritage
and because we are sculpted by evolution.
By looking at these patterns of conservation,
and change within our genome,
we can often decode something about the function
of a region of DNA.
For example, if it codes for protein sequence,
then it has to have this triplet pattern of codons
and you'll find that while there are changes in the region
they preserve this fundamental property of being able to code
for a protein, and we can see that clearly
in the pattern of changes which are allowed
or not allowed.
So that gives us a window,
just by studying comparisons between many pieces of DNA,
into the function of those pieces of DNA.
But we're only seeing the tip of the iceberg here.
We're very much at the beginning
of a long journey, now that we're in the genomics era
and being able to look at all of these genomes
together, of decoding them through
their history, through comparison.
I hope you will consider taking this journey
with us. It's a journey that needs not only biologists,
but computer scientists.
Right now the world is struggling
to be able to write the software code
to create the computer architecture
to be able to compare the full genomes
from hundreds, or thousands, of different species
This is the very edge of our capabilities at this point.
And we can look forward to great innovations,
both in terms of computers and algorithms,
big data, cloud computing, all of these
things will have a say, along with traditional
fields like biology, molecular biology, biochemistry,
and evolution population genetics.
So it's a great time to be involved in this,
and I invite you to this wonderful adventure.