August 21, 2013 • 43 mins
What are genes? What roles do they play in making us who we are? How much do we know about the human genome?
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Episode Transcript
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Speaker 1 (00:00):
Brought to you by Toyota. Let's go places. Welcome to
Forward Thinking. Hey there, and welcome to Forward Thinking, the
podcast that looks at the future and says, carry on
my wayward son. I'm Jovin Strickland, I'm Lauren Bocubon, and
I'm Joe McCormick. And we wanted to kind of talk
(00:21):
about genes and genetics and d n A and chromosomes.
And it's because we have this whole podcast where we're
going to be talking about gene therapy coming up. But
really to understand gene therapy, we kind of need to
lay that foundation first, so a little bit. And yeah,
so for those of you, those of you who who
(00:41):
have been out of middle school science for quite some time,
like me, might need a refresher course, or maybe you
never really studied this. For those of you who have
a significant grounding in this, either educationally or perhaps professionally,
just humor us because we wanted to make sure that
we define in some terms and understood things before we
(01:02):
launched into a full gene therapy discussion. Come on, that
makes it sound a little dry and sterile. We're we're
about to talk about some really huge molecules. I mean,
I mean big, big molecules, Yes, big enough where if
they weren't so darn thin, you would be able to
see them with the naked eye once they are unfurled,
because DNA molecules could be a couple of centimeters long,
(01:24):
depending upon what you harvested them from. Ye, but they're
very very thin, so they wouldn't see them anyway. But
they're quite long. Um. So, early days of modern biology,
you had scientists looking at cells through microscopes, and uh,
(01:44):
normally you wouldn't be able to see things like chromosomes
within the nucleus of a cell except during cellular division,
because at that point the chromosomes kind of get all
compact and they get dark enough where you can see them.
So that led people to think. Specifically, scientists think, huh,
I wonder what that stuff is around around What part
(02:06):
of the timeline was this did you, oh, gosh, this
would be in the nineteen well, nineteen thirties and forties really,
But if you want to talk about the actual evolution
of of of genes and heredity and this sort of
these sort of concepts, you actually have to go back
quite some ways to the mid nineteenth century. Actually this
(02:28):
is interesting and a lot of people don't even know this.
Charles Darwin didn't know anything about jenes no, well maybe
sort of as a concept like the idea of inherited traits,
but didn't know anything about d n A. Right, he
had this practical evidence that that he was being presented
with and that he was thinking about really hard. But
but they had no way of knowing what the discreet
(02:48):
element of transferral of traits actually was. And in fact,
there there were other people working on learning about, you know,
how traits are passed down at the same time, at
the same time, and they didn't. They didn't they didn't
match up. In fact, the first one really Gregor Mendel,
who was an Austrian monk, and uh he decided that
(03:11):
he was going to investigate how traits were passed down
by using hybridized p plants, and he wanted to just see,
you know what determines how certain traits get passed down.
And a lot of experiments in these early days would
only last a few months, maybe a year, and so
(03:33):
you would only have a certain number of generations of
plants to work with. And the general thinking at that
time was that you would get these unusual traits that
would pop up in plants, but that the hybrids would
eventually revert back to the original form of the plant
several generations down the line, like like it would just
be a little side step, but then it would re
(03:53):
orient itself. That well, Gregor Mendel decided to kind of
really look at this, and over the course of about
eight years and thousands and thousands of plants, he discovered
that there were some interesting things going on, that that
there were different types of traits that were being passed on,
and actually started to lay the groundwork for things like
(04:15):
dominant traits versus recessive traits, things that you know, if
if a p plant had once certain type of trait
that was more likely to be passed down than other ones.
And he really started to put all this together, but
no one really gave it much thought, including including himself.
He thought that this was an interesting thing, but didn't
(04:35):
apply it to a wider range of life forms beyond
pe plants. Well, he didn't know about DNA either. No, No,
this is men daily in genetics. So again it's just
based on um sort of phenotypical markers that show up
things you can see with the naked eye parent physical traits.
So he he did, he did figure out the or
(04:58):
he did lay the groundwork for pre dominant traits versus
recessive traits. And he also figured out that the traits
were not necessarily dependent upon one another, right, they were independent.
A lot of traits just had one set of traits
and another set of traits didn't necessarily have to be
present for the next generation to start to exhibit them.
(05:19):
So that was also interesting. Uh. In eighteen sixty nine,
that's when Friedrich Mischer, who was a German chemist, was
the first person to isolate DNA from cell nuclei that's
where you would find DNA generally speaking, And uh, he
wasn't sure what the heck it was, this this sort
(05:41):
of white, acidic substance, and no one was really sure
if it even had a purpose. In fact, for for
years they just sort of discounted it as just like
this is just something that's in cells, but it doesn't
do anything important, and uh, but it's understanding. There was
no way from him to know really. Inties and forties,
(06:02):
that's when you had scientists really looking at it and
trying to figure out exactly what this stuff was. What
was important about it. They began to learn that DNA
was made up of a five sided sugar uh, and
that it also had these base pairings of well, they
didn't even know what it was pairings at the time.
They knew that there were these other polynucleotides inside DNA,
(06:27):
they didn't know the significance of it. And they also
knew that DNA had a protein involved with it. The
protein is the scaffolding that DNA wraps itself around, but
they didn't they weren't sure what significance any of that was.
To take get to about nineteen fifty, that's when a
check scientist named Irvin Cargoff discovered the base composition of
(06:48):
DNA and measured the amount of the four nucleotides you
can find in DNA. And I'll cover that in a minute.
And he also noticed that something interesting that you know,
the four nucleotides, we generally call them A, T, C,
and G for their names. And again I'll go through
the names when I can get my tongue around them.
Can I try? Can I try go for it? Okay,
(07:10):
it's uh oh manin, thiamine, adeni ad and id ad
anine and oh guanne Okay, so how close was I
think I was messing up some idine thymine citazine gun
(07:34):
And then if you're going with RNA, which of course
is the other component we have to talk about eventually, Uh,
arny doesn't have thymine, but it does have ur a
cell and your cell ends up acting pairing, pairing with
at an in the same way thyman does. So it's
you don't have you're really uh, consult your physician. No,
(07:56):
your cell it fulfills that same purpose because what happens
is these these based nucleotides pair with one another. Now,
at this point in nineteen fifty, they didn't know anything
about pairing. What Chargov saw was that if you looked
at the ending and the thyming nucleotides, they were roughly
equivalent to each other. And the same was true for
(08:17):
the site of zine and guani nucleotides. Those were equivalent
to one another. And so this, uh, this gave rise
to what is now known as Chargovs rules, which was
just that if you find a certain amount of one,
then you know that that's the same amount for the
other one. And it also laid the groundwork for later
scientists to kind of figure out about this nucleotide pairing
(08:41):
that the reason why there are equal amounts is because
they pair up in a strand of DNA. So that
takes us up to that. Nineteen fifty two, that's when
Alfred Hershey and Martha Chase really uh they got behind
the idea that it was DNA that carried genetic information,
that it carried this hereditary information, rather than the protein
(09:02):
scaffolding that the DNA was wrapped around, because at the
time no one was really sure and there were some
people who were saying, it's the protein that carries the
hereditary information, not the DNA molecule. And uh so they decided,
should we sort that out? Now? Are we getting to that.
We'll get to it. We'll get to never you fear
trust in Jonathan, Yes, but but trust in specific instant.
(09:26):
There's a lot of molecules in here, all right, all right,
to be fair, all right, So the protein is the
scaffolding that the DNA wraps itself around. Okay, so, and
DNA itself at least is in the business of making proteins. Yes, yes,
so it makes proteins. What technically, what does is really
gives the instructions for amino acids. Which amino acids are
(09:47):
the building blocks for proteins. But I'll get there, trust
me anyway. So, uh, they weren't sure whether or not
it was the protein element or the DNA element that
actually passed down U hereditary information. And so they Hershey
and Chase, who thought it was DNA, decided they would
do an experiment, and so I think there was. They
(10:07):
got some They got some DNA and they from a
bacterial virus called T two. Actually, uh, it would raise
its thumb as it was lowered into lava. Uh. The
T two virus, Actually it has a shred of it's
it's a virus that has a shred of DNA inside
and a little tiny piece of protein inside it as well.
So what Chase and her She did or hers Chase
(10:29):
because it's usually called Hershey Chase experiment. They ended up
inserting a radioactive tag in the DNA of this virus
and then allowed the virus to go ahead and do
its a little viral thing where it would go and
replicate replicate itself. And then they noticed that all the
viruses that were replicated also were radioactive. They had this
radioactive tag. They repeated the experiment by tagging the protein
(10:51):
with this radioactive tag and did the same thing and
saw that the the next generation of viruses did not
have the radioactive tag. Uh huh. They say, this shows
that the DNA is what's passing down this hereditary information,
not the protein. So bite me, although they said in
a much nicer way scientific yes, that was probably whatever
(11:13):
the latin is for biting me, right, it's it's pure viewed.
So that brings us to nineteen fifty three, and this
is when the probably the most famous of the discoveries,
um you could argue for for the whole history of
DNA and jeans it comes about. And that's when the
actual molecular structure of DNA was discovered. The soul Watson, Crick, Franklin,
(11:34):
and Wilkins. Yes, James Watson and Francis Crick are the
one to who are normally credited. It's Watson and Crick.
You always hear Watson and Crick, but they their work
was made possible by the work of two other scientists,
Rosalind Franklin and Maurice Wilkins, who all had been working
on this And without the work of Wilkins and Uh
(11:55):
and Franklin, you wouldn't have had the information Watson Krick
wouldn't have had the information they needed to learn the
actual structure of DNA. UH. Franklin had been using X
ray diffraction to observe living cells and it was that
that gave them the ability to take a look at, uh,
this double helix structure that DNA has, and they could
(12:17):
tell that it was this double helix structure that would
pull apart to make copies of itself during cellular division. UH.
And then if you wanna, you know, the next big, big,
big moment in genes, which will talk about more in
another episode, it was the ninety seven which was the
first sequencing of a complete genome, which was the bacteria
fage f x one seven four. So, um, now we're
(12:41):
going to talk a little bit about what these structures
actually are and what you know, the define some more
terms because there's a lot of confusion when it comes
to DNA, genes, genome, chromosomes, and just kind of use
them interchangeably, right, and and you know it helps to
get get a little more precise. Okay, Well, one clear
distinct shinn' make I think is that gene is sort
(13:03):
of a classification where that we have whereas d N
A as a molecule UM and what so the structure
of DNA, we could talk about that for a little. Sure,
it's like it's like you said, it's a double helix,
so you'd have to imagine kind of a twisted ladder.
Take a ladder and twist in a right handed or
(13:24):
clockwise direction, and so correct me if I'm wrong. But
I think I just I just realized for the first
time that what the ladder is actually built of is
that the sides of the ladder are basically just sugar molecules,
and it's the wrongs of the ladder that contain the
crucial genetic information. Those are the that's the nucleotide pairings. Yeah, so, yeah,
(13:46):
you've got the and. And the reason why the nucleotide
pairings have to be A and T and C and
G is that if you tried to put up any
other type of pairing, the wrongs would be the wrong
width and you wouldn't have of a a stable structure anymore.
The only way the wrungs are of the correct width
so that this double helix structure can remain stable and
(14:08):
remain intact is to have it paired up the way
I said a t n C. And it's the only way. Uh.
DNA of course stands for de oxyde de oxy ribonucleic acid.
I knew I was going to mess that up before
I could get through it once. But deoxy acid. Yeah,
you know, you just had the benefit of hearing me
say it twice. Mr Adenine thyming that one. So they
(14:35):
the acid here has this, Uh, the base pairings they
bond with hydrogen bonds the four nucleotides, right, And it's
the sequence of bonds, the sequence of pairings that create
genetic information. Uh. Not all of DNA is encoded genetic information.
(14:56):
Some of it is behaving in a way that we
don't fully understand yet. It's sometimes it's called junk DNA.
Sometimes it's called non coded DNA. At any rate, it
almost seems like it's, you know, gibberish. That's just there
to break up the genetic coding. Now, when I say
just there to break up, that's what I'm saying from
a from an uninformed perspective, that's what it looks like.
(15:17):
But we may learn in the future that it has
a very specific purpose that we just don't know about yet. Right, Okay, Well,
I think we don't hear the term junk DNA is
often these we just don't know what, so we often
call it noncoding because we we don't recognize it as
coding for specific type of protein. So one, what what
(15:38):
makes DNA so special is a molecule. What makes it
not like any other molecule. There's a lot of things
that make it not like any other molecule. For the fact,
one thing is that this the sequence of bonds, can
actually pass on actual information. These instructions for creating amino acids,
which in turn create proteins, and the proteins are pretty
much what tell your cells what to do and when
(16:00):
they're what makes your body go. It's it's right, it's
it's it's what makes you grow. What makes your your
you know, body parts develop into the body parts that
they are, rather than makes you be you is when
it really comes down, it's the size of your brain pan.
It's also the DNA is in most of our cellular nuclei,
and so essentially the entire record of what makes you
(16:22):
you is in every single nuclei of these cells. Did
you know, though, that the nuclear nuclei aren't the only
part of your cells that have DNA shut your mouth, Yeah, yeah,
that's right, which you get from your mom and not
from your dad at all. Really. Yeah, So you get
your nucleic DNA that that comes from your mom and
(16:44):
your dad, and that's in the nucleus of your cells
and tells tells the rest of your body how to
make itself and what to do. That comes from both parents,
but just from your mom. You get mitochondrial DNA, and
that's a separate little bit of DNA that lives in
the mitochondria and the cells, and the mitochondria of a
all is sort of like the power plant. Sure, yeah, yeah, exactly,
And when you talk about genes, you're really talking about
(17:05):
a specific strip of DNA. It's sort of a think
of it like magnetic tape. For for if you're a
computer storage kind of person. So this would be a
length of magnetic tape upon which there are instructions, and
then there would be noise between the instructions and the
next set of instructions, which are for something totally different, right,
(17:25):
some other some other process. Now, in this case, the
process we're talking about, it's usually to create proteins through
the production of amino acids UM. Now the other thing
you can the other thing that's really important to remember
that genes are like the fundamental unit of heredity. Okay,
so that's sort of like you can think of a
gene as the equivalent of an atom, but only when
(17:48):
we're talking in terms of of heredity. So this is
as small as it gets. Uh. The relationship between genes
and traits is very complex. Uh. There our genes that
can manifest in several different traits. Uh, and then there
are some traits that require multiple genes to manifest, so
(18:09):
it's not a one to one relationship at all. Right.
One thing you can think of making a gene discrete
is that a gene is sort of a section of
information that can have different what are called alleles, and
so that's a different variation on that set of information.
And in a gene pool, there will be multiple alleles.
(18:30):
So you can have one gene and then a different
version of that gene, different version of that gene found
in different individuals. All right. So a human gene is
typically between twenty seven thousand and two million base pairs. Okay,
so those nucleo tide pairings, that's how many are in
a typical gene. Between twenty seven thousand, two million, which
is a huge range. And it's also interesting to know
(18:51):
that a thousand base pairs would technically be enough to
encode most proteins. And that's what these genes are doing
there for the most part, they're meant to encode proteins. Uh.
And so it's interesting to think that the typical genes
and the human seem to be really inefficient. And that's
(19:11):
because there are large parts of genes that are not
meant to encode, and they're they're also really complicated. Most
of them make more than one protein the average is
three actually, right and um and and they are not
they're not really discrete units. They interact with each other
in interesting ways, right and so so here's how they
actually work. So cells make a copy of the gene
(19:34):
through you know, they take the length of DNA where
the genetic information is relevant. This whole process is called transcription.
That copy ends up moving to another part of the
cell where it's used to create a chain of protein
subunits amino acids. That parts called translations. So transcription uses RNA,
that's the copy that is created out of this RNA
(19:55):
is made up of ribonucleotides, and so those bases U
compliment the ones in DNA. But like we said earlier,
there's no thymine, so they uses eurusil instead, which you
and A buying together. So there's no real problem there. Uh. Now,
the genes have protein coding sections called xns and non
coding segments called in tron's. So the RNA section RNA
(20:19):
sections that correspond to in trons, the non coding parts.
Those parts get generally they get removed from the RNA.
It's called splicing. It splices out. It's kind of just
like you know you're splicing film. You take out the
part you don't want, and then you merge the other
two pieces together. So that way you just have the
coding parts left, the xns in other words, and that
(20:39):
becomes what is known as messenger RNA. Well, then you've
got these other bits of RNA, uh, the the the
transfer ribonucleic acid or t RNA. So you've got your
messenger RNA, you got your transfer ribonucleic acid. Uh. You
get the two of them together, and it's like a
(21:00):
spaceship docking with a space station. So you look at
these three base pair will not even base pair uh
three exxons. So you code this by the three letters
that they might be like g G G or it
could be g U A or so anyway, you you
get those those three codes, the appropriate t RNA will
(21:24):
doc with that, and that gives the t RNA the
instruction to make the amino acid whatever it's supposed to
be according to the messenger RNA. So the messenger RNA
is essentially the recipe. The t RNA all will only
produce one specific amino acid, and it only will work
if they can doc with that part of the m RNA.
It'll build a protein based on all these amino acid chains.
(21:47):
And uh, and that's the basis there. So you've got
your amino acids and proteins. That gives the instructions for
everything else that's going on. Really and uh, there's your
there's your basic genes and how those genes work and
how they replicate proteins. Now, let's talk about chromosomes. So
we've we've got DNA. That's the molecule. We've got the genes.
(22:09):
That's lengths on the molecule that give instructions for things
like protein generation. Chromosomes are essentially packages of genes, all right,
so life forms have chromosomes, they don't all have the
same types of chromosomes or the same number of chromosomes. Uh.
Humans have twenty three pairs of chromosomes, one pair of
(22:30):
that sex chromosomes. So uh, that's different if you're female
or male. Obviously for females too, X chromosomes. If you're male,
it's an X and Y chromosome. Why because we like you.
And then the rest of the chromosomes are all other types, right,
And you've got these are the ones that uh, you
(22:52):
have one pair you have inherited from your father, and
one pair you've inherited from your one half of the
pair I should say you've inherited from your mother. And
so you've got these packages of genes. They are of
different sizes. Uh, they have different types of genes in them.
Things that would be important for very related elements in
(23:16):
our lives, like things that might be uh important instructions
for the production of one type of cell that's very
similar to another type of cell could be found in
totally different chromosomes. So it's not like, you know, it's
not like you would go to a library and pick
out a book and like everything. There's no decimal system
new it's kind of all jumbled up, but it makes
(23:37):
sense to biology it were, or sense in the sense
that it works. And we're here. Yes, So that those
are your basic definitions, right, You've got your DNA, your genes,
your amino acids and proteins, you've got your chromosomes. Essentially
the collection of all this information we call the genome
for a specific life form, right, every every human genome,
(24:02):
there's a mouse genome, there's an E. Coli genome exactly.
So there we go. That's that's my I'm done, I've defined.
I'm back in a way. Take over. Would you guys
like to talk about the sequencing of the human genome please?
That sounds wonderful, excellent. Let us do that pretty recent,
wasn't it? That was extremely recent? That was that thing
(24:22):
in two thousand three that I was talking about. Um
the Human Genome Project was kicked off October one of
ninet so basically after the Department of Energy helped create
the atomic bomb. Um Us Congress said, hey, guys, this
is some some wacky stuff that you have created, and
we would really like you to apply some of this
amazing scientific technology and know how that you have to
(24:45):
figuring out how this horrific creation is screwing up our genetics. Um.
And they technically said this to the Atomic Energy Commission
and the Energy Research and Development Administration, which were the
predecessors to the Department of Energy. But at any rate,
the the what what became the Department of Energy got
together with the National Institutes of Health and started the
(25:07):
Human Genome Project, which was to sequence the entire human genome,
which enormous, enormous tasks, which is a which is a
big deal. I mean, at the time, they thought that
there were a hundred and fifty thousand genes making up
the genomes. As it turns out, like Jonathan said that
it's more like so, human chromosomes range in size from
(25:32):
fifty million to three hundred million base pairs, and in
order to to sequence out the genome, you have to
split that down um by a process that's called bacterial
artificial chromosome UH sequencing into into smaller, smaller little bits
of base pair information only hundred and fifty thousand base
(25:55):
pairs a GOO. This was super complicated because, like I said,
you know, we have identified genes and figured out what
some genes do and what you know, what they're encoded
to do, what kind of proteins there they make. But
there's a lot of replicated information within human genes. There
there are a whole segments that you look at, Like
(26:16):
when I made that talk about the magnetic tape, it's
as if like let's say that we're talking about magnet
tape and it's an old cassette tape that has music
on it. It would be like you're listening to an
album and three songs after the first song, like, you
listen the first song like that's pretty good. Three more
songs go by, and then the first song comes on again,
like why did they do it twice? The human gene
genome is kind of filled with stuff like that, including
(26:39):
stuff that we still call non coding DNA because we
don't know if it actually is doing anything all right,
So they had to they had to split up the
total genome into these kind of workable fragments. They split
it further than I just mentioned, know what's called subclones,
and then let these bacteria replicate these little pieces of
DNA and in a way that they can really get
in and figure out what the pairs are doing and
(27:01):
and and how everything fits together. So they wind up
with a with A, B, A C library and and
from that, you know, have have determined the sequences of
the chemical base pairs that make up DNA and have
put all of this information into databases for researchers to
play around with. Yeah, it's also interesting to me that
(27:22):
early on, when they were first identifying genes, it was
at such a slow pace relatively speaking, that there were
people who thought that it was going to take a
century to map out the human genome. The projected timeline
for the project was from two thousand and five. They
completed it two years early in two thousand three, and
(27:42):
um about point three billion under budget. So and that
was so part of it is because they could not
anticipate improvements in the processes. I mean, we we never can, right.
We never think in ten years we'll be able to
do this much more quickly because of X. We usually
think in terms of what we're capable of doing right now,
(28:05):
and that's how we project out how long it's going
to take us. If we're lucky, then technology and science
progresses at such a rate that the task becomes less overwhelming. Also,
we learned that it wasn't as big a job as
we as we original thought. Yeah, well it's um, you know,
intracellular biology progressed and really dovetailed with the computer industry,
(28:27):
and if we had not had the kind of developments
and computers, then shortly we've taken Yeah, that's what I
was just thinking of starting in the early nineties. I mean,
think of how crappy computers were back then. But another
interesting thing, mine still ran on a O L that's
not how that so another wow, it was like a
(28:49):
thousand people cried out in anguish. I'm imagining that they're
doing the Human Genome project with like the desktop calculator
application and Windows three point one. Well, you know what's
also interesting is that this is not directly related to
the Human Genome project, but it's it's a similar field. Uh.
You know, I was talking about proteins earlier, these long
(29:10):
chains of amino acids. One of the other interesting things
about proteins is that they fold, and when they fold,
that's what gives them certain features of property properties exactly,
thank you. And we don't fully understand the folding process. Well,
the folding is determined we think by the amino acid sequence, right,
So it's it's a long chain and you can imagine
(29:31):
that it's like a chain of letters in a particular sequence, right, um,
and what order the letters come in determines the three
dimensional shape that the protein twists up into. Right. And
there's actually a really cool project called Folding at Home.
Have you guys heard of this. Folding at Home is
one of those distributed computing networks where, uh, you can
(29:52):
participate in helping scientists determine what proteins will take, what shapes,
why they do it, what kind of properties they have.
It's really be useful for things like potential medical uses.
So what happens is it's one of those that you
sign up for this project, you install some software, and
then your computer, when it's idle, is actually working on
these various computer models of proteins, and as it solves
(30:16):
these different models, it then sends that information back off
to the centralized server which collects it and you know,
vets everything that comes back in. Keep in mind, this
is all automatic. You're not putting in any even put here,
but it vets it all and then essentially puts it
in a database. So that the body of knowledge about
proteins and how they fold grows dramatically over time as
(30:39):
more and more people joined this project. I love that
kind of distributed simulation. Just that that's steady, right, But anyway,
that's that's getting even further afield. So back to the
human genome. So along with sequencing the human genome, the
project led to UM a lot of other creatures genomes
being sequenced UM like I said earlier, ecal um, mice,
(31:00):
the fruit fly, stuff like that, UM to to help
us start working in the larger gene field. And basically
all of the research that's happening today and in gene
therapy and in genetics is because of the research that
was pioneered in the Human Genome project. I think that's
really useful having the full genomic information about like fruit
(31:22):
flies or icola. I mean, you can run so many
generations of those organisms in the lab, which you can't
do with humans and and probably can't even realistically do.
And and usually the genomes are a lot shorter on
on more simple organisms, which is interesting. It's not always
the case because there are like like the number of
genes you can find in certain creatures can be dramatically
(31:46):
larger than that of UM, or dramatically more than what
you would find in humans. It's the plexity doesn't necessarily translate.
It does not and uh and it depends on I mean, like,
for example, the platypus has ten sex chromosomes. Yeah, it does.
I don't even know what that's for. Only platypus is no.
(32:07):
They have a they have a don't ask, don't quack policy.
Do they know? What do they do? They pretty much
don't do anything. Have you not watched They don't do
very much have some kind of crazy sex. Al Right, guys, guy,
if you know what a platypus, if you know the
platypus sounds like I want to hear it, let me
let me know. Okay, all right, that's fair. So so
(32:27):
the first person who can send us a sound of
a platypus, when's Laurence applause? Yeah, okay. So we've mentioned
some basic research in the abstract, but what can you
actually do with genetic genetic information? Like, how do you
apply it practically? Gosh, Joe, I don't know that was
your segment. I was hoping you'd tell us. So one
(32:49):
of the things we want to talk about was this
idea of DNA matching, right, the idea of being able
to to I mean, think about if you are able
to understand your genetic information, if you're able to know
that this sequence is something that was inherited, then that
means that you can find links between you and other people.
It means that it could be useful for things like
(33:11):
a genealogy. It can be useful for things like paternity testing.
It can be useful for things like someone left some
blood behind at this crime scene. I wonder whose blood
this is. There are a lot of different potentials. Yeah.
So one of the interesting things I was thinking about
was was paternity testing, and I wondered, how did they
(33:34):
do this before they had genetic testing, and then furthermore,
just how does it actually work? But it so, one
of the things I found that I thought was interesting
was before they had genetic paternity tests, they would often
use blood type testing. Okay, that makes you know enough sense,
I suppose. I mean, it's it's pretty inaccurate considering the
(33:56):
number of humans that are out there with similar blood types. Yeah,
they didn't have a lot to work with. But so
with blood testing, so you have a scheme of blood typing,
and they're actually different types of blood typing. There's not
just one type of Uh. One thing you can look
at is like the A B O antigens, right um,
And so that's your system where you can be like
(34:17):
A A B oh um and O positive negative. And
so these things are inherited. But some of these are
dominant and some are recessive. And once we had a
Mendalian genetic model for how blood types A B O
blood types are inherited. You could use that to say, well,
(34:38):
you couldn't identify for sure that somebody was somebody's kid,
but you could rule out that they could be their kid. Right,
so someone narrowed down the field. Well, one thing I
read about it apparently this happened to Charlie Chaplin. Like
somebody said that Charlie Chaplin had had fathered her child
and he denied it. And uh, and the genetic not genetic.
(35:01):
It was before genetic testing that the blood type testing
said that he was not the father um in a
very more Povich kind of way. But but apparently they
couldn't use this in the courts at that time, and
so he ended up paying child support anyway. So, so
tell me about the the progression from this fairly primitive
(35:23):
in the grand scheme of things approach to matching to
DNA matching. Well, now that we've got d N A,
we've got a much higher uh, we've got more things
to match, basically to give you a stronger piece of confidence.
So let's say that your blood type test only shows agreement. Well,
(35:44):
that doesn't narrow it down much at all, like we
talked about. But let's say you can identify a certain
number of genetic markers between the suspected father and the
child and look for matches. Now, if you only have
a suspected father and the child, it's a little bit
harder to get a positive match, um, because you can
(36:06):
look at a child and say, like they say, they
have a gene like A and B, and um, the
father has genes B and C. You don't know if
that be in the child necessarily came from the father. Yeah. Um,
But you can get a much better idea if you
(36:30):
also have the mother's DNA and find that in that
same genetic marker the mother does not have B. So
there you have a much higher level of confidence. You
do this over multiple genetic markers, and if you keep
finding matches between the father and the child that do
not match with the mother's DNA, then you have a
(36:53):
near certainty. Um, the more markers you measure, the higher
certainty you can get. What they don't do, though, is
they don't compare the entire genome, because, as we've talked about,
lots of it just wouldn't make any difference, and and
lots of it would be identical anyway, because it's identical
in everybody. Also, processing all of that would be way
more work than is in any way necessary. Yeah. Well,
(37:16):
in fact, all human beings have it's like ninety nine
point nine percent the same DNA, and right, it'd be
like taking a book that's a thousand pages long, and
nine hundred and ninety nine of those pages are going
to be identical. They kind of the identical words on them.
But if you but there's one page worth of words
that will be different, and you have to go through
(37:37):
the whole thing. They're spread out throughout the entire For
those words are spread out, Yeah, it's it's our Our
code differs it around um ten million points out of
you know, three point two billion. Yeah, that's right. So
it would be like the genetic expertise. What you do
there is you open the book to a certain page
that you already know is going to have a variant
on word number three on this page, and then you
(38:00):
can compare it from there, and then you just do
that as many times as possible on down the line. Now,
of course, once you get a certain number of matches,
it's it's so certain that you really just don't need
to mess with it anymore. Sure that that the odds
of any other person it's a are are just incredibly tiny.
This is from a BBC right up. So forensic DNA
(38:23):
test and this is it's talking about forensic d so
that this isn't a paternity business. Yeah, it would be
a crime. But so to identify a blood sample to
the same person, you'd examine like six to ten genetic
markers and they say the chances of two unrelated people
having the same matches in those cases is one and
(38:43):
one billion. Those are those are some pretty high odds there, um.
And of course, so that brings up the other thing.
Genetic matching is often often also used in forensic analysis,
so you can use it in the court system to
try to prove somebody guilt. And I know that this
is difficult in a lot of cases because there's frustration
(39:06):
that I think both sides in court cases have the
juries don't really understand DNA evidence in a lot of cases,
and they value they can value eyewitness testimony above DNA evidence.
I mean, there are plenty of cases where either someone
was pronounced guilty or not guilty, and there have been
(39:26):
a lot of there's been a lot of criticism in
in cases all across the board where it seemed like
a jury was ignoring any sort of DNA evidence in
favor of eyewitness testimony. And one of the things we
can tell you a lot about is that human memory
is not infallible. You can't. You can't just think that
(39:47):
human memory is perfect. And even if someone is being
completely honest when they're on the stand, they could be
telling that doesn't mean that they're not wrong. Yeah, they
could be telling something that's totally wrong. It's essentially a falsehood,
but it's not one that they intended to be false.
It's just that they remember it differently than how it
actually happened. Whereas DNA testing, assuming everything is on the
(40:07):
up and up right, assuming there's no tampering, assuming that
everyone was following proper procedure and proper controls, is far
more reliable. But that's not generally understood. Yeah, I mean,
if you have a reputable lab doing this, and especially
if you get redundant results from multiple labs and they're
testing a large number of markers, it's going to be right,
(40:31):
you know. Yeah, again, unless you're identical twin committed the crime,
or or unless unless you've been framed. Yeah, right right,
that's that's the other that's the only other real option.
So identical twins are not always genetically identical. That's yeah,
that's true. Interesting point. Yeah, it's it's those you know
that that you know, ten million different differentiation points are
(40:54):
can be can be different. I think monos I gottic
twins are. They're sort of generally con sidered genetically identical.
But is it a case where what there is variation
but there's so little variation it's negligible, or or what's
the deal. Well, there's um those differences that I was
talking about are called single nucleotide polymorphisms, and and so
(41:17):
few of them can be different. But you know that
that for for all phenotype, all visual intents and purposes
to people would be identical. But but for example, some
some identical twins are more likely to get certain mental
health issues or physical issues like one over the other. Yeah,
so one might could that could that also be influenced
(41:40):
by environmental factors like causing genetic changes? Oh yeah, you know,
our genes definitely can undergo changes that aren't you know.
It's not like when you inherit your genes that that's
the way they are for the rest of your life.
They can change and do change due to lots of
different factors, including environmental factors. Uh. That's that's whole the
(42:00):
process of mutation, which we will cover in depth in
another episode. Join us next time when we talk about
gene therapy and x men. Yeah, that's right, that's coming
up in the next episode. We're really excited to talk
about it. So you guys have to wait a couple
of days, but we get to wait all of you know,
a couple of minutes. So we're gonna wrap this up. Guys.
If you have any suggestions for future episodes of Forward Thinking,
(42:21):
go to f W thinking dot com. That's where we've
got all the podcast blog posts, we've got links to
other articles. You can get in touch with us through there,
and we are excited to hear from you and for
you to be come fart of this conversation about the
future and what's gonna be awesome about it, and we
will talk to you again really soon. For more on
(42:44):
this topic in the future of technology, visit forward thinking
dot Com, brought to you by Toyota to go places
Brought to you by Toyota. Let's go places. Welcome to
Forward Thinking. Hey there, and welcome to Forward Thinking, the
podcast that looks at the future and says, carry on
my wayward son. I'm Jovin Strickland, I'm Lauren Bocubon, and
I'm Joe McCormick. And we wanted to kind of talk
(00:21):
about genes and genetics and d n A and chromosomes.
And it's because we have this whole podcast where we're
going to be talking about gene therapy coming up. But
really to understand gene therapy, we kind of need to
lay that foundation first, so a little bit. And yeah,
so for those of you, those of you who who
(00:41):
have been out of middle school science for quite some time,
like me, might need a refresher course, or maybe you
never really studied this. For those of you who have
a significant grounding in this, either educationally or perhaps professionally,
just humor us because we wanted to make sure that
we define in some terms and understood things before we
(01:02):
launched into a full gene therapy discussion. Come on, that
makes it sound a little dry and sterile. We're we're
about to talk about some really huge molecules. I mean,
I mean big, big molecules, Yes, big enough where if
they weren't so darn thin, you would be able to
see them with the naked eye once they are unfurled,
because DNA molecules could be a couple of centimeters long,
(01:24):
depending upon what you harvested them from. Ye, but they're
very very thin, so they wouldn't see them anyway. But
they're quite long. Um. So, early days of modern biology,
you had scientists looking at cells through microscopes, and uh,
(01:44):
normally you wouldn't be able to see things like chromosomes
within the nucleus of a cell except during cellular division,
because at that point the chromosomes kind of get all
compact and they get dark enough where you can see them.
So that led people to think. Specifically, scientists think, huh,
I wonder what that stuff is around around What part
(02:06):
of the timeline was this did you, oh, gosh, this
would be in the nineteen well, nineteen thirties and forties really,
But if you want to talk about the actual evolution
of of of genes and heredity and this sort of
these sort of concepts, you actually have to go back
quite some ways to the mid nineteenth century. Actually this
(02:28):
is interesting and a lot of people don't even know this.
Charles Darwin didn't know anything about jenes no, well maybe
sort of as a concept like the idea of inherited traits,
but didn't know anything about d n A. Right, he
had this practical evidence that that he was being presented
with and that he was thinking about really hard. But
but they had no way of knowing what the discreet
(02:48):
element of transferral of traits actually was. And in fact,
there there were other people working on learning about, you know,
how traits are passed down at the same time, at
the same time, and they didn't. They didn't they didn't
match up. In fact, the first one really Gregor Mendel,
who was an Austrian monk, and uh he decided that
(03:11):
he was going to investigate how traits were passed down
by using hybridized p plants, and he wanted to just see,
you know what determines how certain traits get passed down.
And a lot of experiments in these early days would
only last a few months, maybe a year, and so
(03:33):
you would only have a certain number of generations of
plants to work with. And the general thinking at that
time was that you would get these unusual traits that
would pop up in plants, but that the hybrids would
eventually revert back to the original form of the plant
several generations down the line, like like it would just
be a little side step, but then it would re
(03:53):
orient itself. That well, Gregor Mendel decided to kind of
really look at this, and over the course of about
eight years and thousands and thousands of plants, he discovered
that there were some interesting things going on, that that
there were different types of traits that were being passed on,
and actually started to lay the groundwork for things like
(04:15):
dominant traits versus recessive traits, things that you know, if
if a p plant had once certain type of trait
that was more likely to be passed down than other ones.
And he really started to put all this together, but
no one really gave it much thought, including including himself.
He thought that this was an interesting thing, but didn't
(04:35):
apply it to a wider range of life forms beyond
pe plants. Well, he didn't know about DNA either. No, No,
this is men daily in genetics. So again it's just
based on um sort of phenotypical markers that show up
things you can see with the naked eye parent physical traits.
So he he did, he did figure out the or
(04:58):
he did lay the groundwork for pre dominant traits versus
recessive traits. And he also figured out that the traits
were not necessarily dependent upon one another, right, they were independent.
A lot of traits just had one set of traits
and another set of traits didn't necessarily have to be
present for the next generation to start to exhibit them.
(05:19):
So that was also interesting. Uh. In eighteen sixty nine,
that's when Friedrich Mischer, who was a German chemist, was
the first person to isolate DNA from cell nuclei that's
where you would find DNA generally speaking, And uh, he
wasn't sure what the heck it was, this this sort
(05:41):
of white, acidic substance, and no one was really sure
if it even had a purpose. In fact, for for
years they just sort of discounted it as just like
this is just something that's in cells, but it doesn't
do anything important, and uh, but it's understanding. There was
no way from him to know really. Inties and forties,
(06:02):
that's when you had scientists really looking at it and
trying to figure out exactly what this stuff was. What
was important about it. They began to learn that DNA
was made up of a five sided sugar uh, and
that it also had these base pairings of well, they
didn't even know what it was pairings at the time.
They knew that there were these other polynucleotides inside DNA,
(06:27):
they didn't know the significance of it. And they also
knew that DNA had a protein involved with it. The
protein is the scaffolding that DNA wraps itself around, but
they didn't they weren't sure what significance any of that was.
To take get to about nineteen fifty, that's when a
check scientist named Irvin Cargoff discovered the base composition of
(06:48):
DNA and measured the amount of the four nucleotides you
can find in DNA. And I'll cover that in a minute.
And he also noticed that something interesting that you know,
the four nucleotides, we generally call them A, T, C,
and G for their names. And again I'll go through
the names when I can get my tongue around them.
Can I try? Can I try go for it? Okay,
(07:10):
it's uh oh manin, thiamine, adeni ad and id ad
anine and oh guanne Okay, so how close was I
think I was messing up some idine thymine citazine gun
(07:34):
And then if you're going with RNA, which of course
is the other component we have to talk about eventually, Uh,
arny doesn't have thymine, but it does have ur a
cell and your cell ends up acting pairing, pairing with
at an in the same way thyman does. So it's
you don't have you're really uh, consult your physician. No,
(07:56):
your cell it fulfills that same purpose because what happens
is these these based nucleotides pair with one another. Now,
at this point in nineteen fifty, they didn't know anything
about pairing. What Chargov saw was that if you looked
at the ending and the thyming nucleotides, they were roughly
equivalent to each other. And the same was true for
(08:17):
the site of zine and guani nucleotides. Those were equivalent
to one another. And so this, uh, this gave rise
to what is now known as Chargovs rules, which was
just that if you find a certain amount of one,
then you know that that's the same amount for the
other one. And it also laid the groundwork for later
scientists to kind of figure out about this nucleotide pairing
(08:41):
that the reason why there are equal amounts is because
they pair up in a strand of DNA. So that
takes us up to that. Nineteen fifty two, that's when
Alfred Hershey and Martha Chase really uh they got behind
the idea that it was DNA that carried genetic information,
that it carried this hereditary information, rather than the protein
(09:02):
scaffolding that the DNA was wrapped around, because at the
time no one was really sure and there were some
people who were saying, it's the protein that carries the
hereditary information, not the DNA molecule. And uh so they decided,
should we sort that out? Now? Are we getting to that.
We'll get to it. We'll get to never you fear
trust in Jonathan, Yes, but but trust in specific instant.
(09:26):
There's a lot of molecules in here, all right, all right,
to be fair, all right, So the protein is the
scaffolding that the DNA wraps itself around. Okay, so, and
DNA itself at least is in the business of making proteins. Yes, yes,
so it makes proteins. What technically, what does is really
gives the instructions for amino acids. Which amino acids are
(09:47):
the building blocks for proteins. But I'll get there, trust
me anyway. So, uh, they weren't sure whether or not
it was the protein element or the DNA element that
actually passed down U hereditary information. And so they Hershey
and Chase, who thought it was DNA, decided they would
do an experiment, and so I think there was. They
(10:07):
got some They got some DNA and they from a
bacterial virus called T two. Actually, uh, it would raise
its thumb as it was lowered into lava. Uh. The
T two virus, Actually it has a shred of it's
it's a virus that has a shred of DNA inside
and a little tiny piece of protein inside it as well.
So what Chase and her She did or hers Chase
(10:29):
because it's usually called Hershey Chase experiment. They ended up
inserting a radioactive tag in the DNA of this virus
and then allowed the virus to go ahead and do
its a little viral thing where it would go and
replicate replicate itself. And then they noticed that all the
viruses that were replicated also were radioactive. They had this
radioactive tag. They repeated the experiment by tagging the protein
(10:51):
with this radioactive tag and did the same thing and
saw that the the next generation of viruses did not
have the radioactive tag. Uh huh. They say, this shows
that the DNA is what's passing down this hereditary information,
not the protein. So bite me, although they said in
a much nicer way scientific yes, that was probably whatever
(11:13):
the latin is for biting me, right, it's it's pure viewed.
So that brings us to nineteen fifty three, and this
is when the probably the most famous of the discoveries,
um you could argue for for the whole history of
DNA and jeans it comes about. And that's when the
actual molecular structure of DNA was discovered. The soul Watson, Crick, Franklin,
(11:34):
and Wilkins. Yes, James Watson and Francis Crick are the
one to who are normally credited. It's Watson and Crick.
You always hear Watson and Crick, but they their work
was made possible by the work of two other scientists,
Rosalind Franklin and Maurice Wilkins, who all had been working
on this And without the work of Wilkins and Uh
(11:55):
and Franklin, you wouldn't have had the information Watson Krick
wouldn't have had the information they needed to learn the
actual structure of DNA. UH. Franklin had been using X
ray diffraction to observe living cells and it was that
that gave them the ability to take a look at, uh,
this double helix structure that DNA has, and they could
(12:17):
tell that it was this double helix structure that would
pull apart to make copies of itself during cellular division. UH.
And then if you wanna, you know, the next big, big,
big moment in genes, which will talk about more in
another episode, it was the ninety seven which was the
first sequencing of a complete genome, which was the bacteria
fage f x one seven four. So, um, now we're
(12:41):
going to talk a little bit about what these structures
actually are and what you know, the define some more
terms because there's a lot of confusion when it comes
to DNA, genes, genome, chromosomes, and just kind of use
them interchangeably, right, and and you know it helps to
get get a little more precise. Okay, Well, one clear
distinct shinn' make I think is that gene is sort
(13:03):
of a classification where that we have whereas d N
A as a molecule UM and what so the structure
of DNA, we could talk about that for a little. Sure,
it's like it's like you said, it's a double helix,
so you'd have to imagine kind of a twisted ladder.
Take a ladder and twist in a right handed or
(13:24):
clockwise direction, and so correct me if I'm wrong. But
I think I just I just realized for the first
time that what the ladder is actually built of is
that the sides of the ladder are basically just sugar molecules,
and it's the wrongs of the ladder that contain the
crucial genetic information. Those are the that's the nucleotide pairings. Yeah, so, yeah,
(13:46):
you've got the and. And the reason why the nucleotide
pairings have to be A and T and C and
G is that if you tried to put up any
other type of pairing, the wrongs would be the wrong
width and you wouldn't have of a a stable structure anymore.
The only way the wrungs are of the correct width
so that this double helix structure can remain stable and
(14:08):
remain intact is to have it paired up the way
I said a t n C. And it's the only way. Uh.
DNA of course stands for de oxyde de oxy ribonucleic acid.
I knew I was going to mess that up before
I could get through it once. But deoxy acid. Yeah,
you know, you just had the benefit of hearing me
say it twice. Mr Adenine thyming that one. So they
(14:35):
the acid here has this, Uh, the base pairings they
bond with hydrogen bonds the four nucleotides, right, And it's
the sequence of bonds, the sequence of pairings that create
genetic information. Uh. Not all of DNA is encoded genetic information.
(14:56):
Some of it is behaving in a way that we
don't fully understand yet. It's sometimes it's called junk DNA.
Sometimes it's called non coded DNA. At any rate, it
almost seems like it's, you know, gibberish. That's just there
to break up the genetic coding. Now, when I say
just there to break up, that's what I'm saying from
a from an uninformed perspective, that's what it looks like.
(15:17):
But we may learn in the future that it has
a very specific purpose that we just don't know about yet. Right, Okay, Well,
I think we don't hear the term junk DNA is
often these we just don't know what, so we often
call it noncoding because we we don't recognize it as
coding for specific type of protein. So one, what what
(15:38):
makes DNA so special is a molecule. What makes it
not like any other molecule. There's a lot of things
that make it not like any other molecule. For the fact,
one thing is that this the sequence of bonds, can
actually pass on actual information. These instructions for creating amino acids,
which in turn create proteins, and the proteins are pretty
much what tell your cells what to do and when
(16:00):
they're what makes your body go. It's it's right, it's
it's it's what makes you grow. What makes your your
you know, body parts develop into the body parts that
they are, rather than makes you be you is when
it really comes down, it's the size of your brain pan.
It's also the DNA is in most of our cellular nuclei,
and so essentially the entire record of what makes you
(16:22):
you is in every single nuclei of these cells. Did
you know, though, that the nuclear nuclei aren't the only
part of your cells that have DNA shut your mouth, Yeah, yeah,
that's right, which you get from your mom and not
from your dad at all. Really. Yeah, So you get
your nucleic DNA that that comes from your mom and
(16:44):
your dad, and that's in the nucleus of your cells
and tells tells the rest of your body how to
make itself and what to do. That comes from both parents,
but just from your mom. You get mitochondrial DNA, and
that's a separate little bit of DNA that lives in
the mitochondria and the cells, and the mitochondria of a
all is sort of like the power plant. Sure, yeah, yeah, exactly,
And when you talk about genes, you're really talking about
(17:05):
a specific strip of DNA. It's sort of a think
of it like magnetic tape. For for if you're a
computer storage kind of person. So this would be a
length of magnetic tape upon which there are instructions, and
then there would be noise between the instructions and the
next set of instructions, which are for something totally different, right,
(17:25):
some other some other process. Now, in this case, the
process we're talking about, it's usually to create proteins through
the production of amino acids UM. Now the other thing
you can the other thing that's really important to remember
that genes are like the fundamental unit of heredity. Okay,
so that's sort of like you can think of a
gene as the equivalent of an atom, but only when
(17:48):
we're talking in terms of of heredity. So this is
as small as it gets. Uh. The relationship between genes
and traits is very complex. Uh. There our genes that
can manifest in several different traits. Uh, and then there
are some traits that require multiple genes to manifest, so
(18:09):
it's not a one to one relationship at all. Right.
One thing you can think of making a gene discrete
is that a gene is sort of a section of
information that can have different what are called alleles, and
so that's a different variation on that set of information.
And in a gene pool, there will be multiple alleles.
(18:30):
So you can have one gene and then a different
version of that gene, different version of that gene found
in different individuals. All right. So a human gene is
typically between twenty seven thousand and two million base pairs. Okay,
so those nucleo tide pairings, that's how many are in
a typical gene. Between twenty seven thousand, two million, which
is a huge range. And it's also interesting to know
(18:51):
that a thousand base pairs would technically be enough to
encode most proteins. And that's what these genes are doing
there for the most part, they're meant to encode proteins. Uh.
And so it's interesting to think that the typical genes
and the human seem to be really inefficient. And that's
(19:11):
because there are large parts of genes that are not
meant to encode, and they're they're also really complicated. Most
of them make more than one protein the average is
three actually, right and um and and they are not
they're not really discrete units. They interact with each other
in interesting ways, right and so so here's how they
actually work. So cells make a copy of the gene
(19:34):
through you know, they take the length of DNA where
the genetic information is relevant. This whole process is called transcription.
That copy ends up moving to another part of the
cell where it's used to create a chain of protein
subunits amino acids. That parts called translations. So transcription uses RNA,
that's the copy that is created out of this RNA
(19:55):
is made up of ribonucleotides, and so those bases U
compliment the ones in DNA. But like we said earlier,
there's no thymine, so they uses eurusil instead, which you
and A buying together. So there's no real problem there. Uh. Now,
the genes have protein coding sections called xns and non
coding segments called in tron's. So the RNA section RNA
(20:19):
sections that correspond to in trons, the non coding parts.
Those parts get generally they get removed from the RNA.
It's called splicing. It splices out. It's kind of just
like you know you're splicing film. You take out the
part you don't want, and then you merge the other
two pieces together. So that way you just have the
coding parts left, the xns in other words, and that
(20:39):
becomes what is known as messenger RNA. Well, then you've
got these other bits of RNA, uh, the the the
transfer ribonucleic acid or t RNA. So you've got your
messenger RNA, you got your transfer ribonucleic acid. Uh. You
get the two of them together, and it's like a
(21:00):
spaceship docking with a space station. So you look at
these three base pair will not even base pair uh
three exxons. So you code this by the three letters
that they might be like g G G or it
could be g U A or so anyway, you you
get those those three codes, the appropriate t RNA will
(21:24):
doc with that, and that gives the t RNA the
instruction to make the amino acid whatever it's supposed to
be according to the messenger RNA. So the messenger RNA
is essentially the recipe. The t RNA all will only
produce one specific amino acid, and it only will work
if they can doc with that part of the m RNA.
It'll build a protein based on all these amino acid chains.
(21:47):
And uh, and that's the basis there. So you've got
your amino acids and proteins. That gives the instructions for
everything else that's going on. Really and uh, there's your
there's your basic genes and how those genes work and
how they replicate proteins. Now, let's talk about chromosomes. So
we've we've got DNA. That's the molecule. We've got the genes.
(22:09):
That's lengths on the molecule that give instructions for things
like protein generation. Chromosomes are essentially packages of genes, all right,
so life forms have chromosomes, they don't all have the
same types of chromosomes or the same number of chromosomes. Uh.
Humans have twenty three pairs of chromosomes, one pair of
(22:30):
that sex chromosomes. So uh, that's different if you're female
or male. Obviously for females too, X chromosomes. If you're male,
it's an X and Y chromosome. Why because we like you.
And then the rest of the chromosomes are all other types, right,
And you've got these are the ones that uh, you
(22:52):
have one pair you have inherited from your father, and
one pair you've inherited from your one half of the
pair I should say you've inherited from your mother. And
so you've got these packages of genes. They are of
different sizes. Uh, they have different types of genes in them.
Things that would be important for very related elements in
(23:16):
our lives, like things that might be uh important instructions
for the production of one type of cell that's very
similar to another type of cell could be found in
totally different chromosomes. So it's not like, you know, it's
not like you would go to a library and pick
out a book and like everything. There's no decimal system
new it's kind of all jumbled up, but it makes
(23:37):
sense to biology it were, or sense in the sense
that it works. And we're here. Yes, So that those
are your basic definitions, right, You've got your DNA, your genes,
your amino acids and proteins, you've got your chromosomes. Essentially
the collection of all this information we call the genome
for a specific life form, right, every every human genome,
(24:02):
there's a mouse genome, there's an E. Coli genome exactly.
So there we go. That's that's my I'm done, I've defined.
I'm back in a way. Take over. Would you guys
like to talk about the sequencing of the human genome please?
That sounds wonderful, excellent. Let us do that pretty recent,
wasn't it? That was extremely recent? That was that thing
(24:22):
in two thousand three that I was talking about. Um
the Human Genome Project was kicked off October one of
ninet so basically after the Department of Energy helped create
the atomic bomb. Um Us Congress said, hey, guys, this
is some some wacky stuff that you have created, and
we would really like you to apply some of this
amazing scientific technology and know how that you have to
(24:45):
figuring out how this horrific creation is screwing up our genetics. Um.
And they technically said this to the Atomic Energy Commission
and the Energy Research and Development Administration, which were the
predecessors to the Department of Energy. But at any rate,
the the what what became the Department of Energy got
together with the National Institutes of Health and started the
(25:07):
Human Genome Project, which was to sequence the entire human genome,
which enormous, enormous tasks, which is a which is a
big deal. I mean, at the time, they thought that
there were a hundred and fifty thousand genes making up
the genomes. As it turns out, like Jonathan said that
it's more like so, human chromosomes range in size from
(25:32):
fifty million to three hundred million base pairs, and in
order to to sequence out the genome, you have to
split that down um by a process that's called bacterial
artificial chromosome UH sequencing into into smaller, smaller little bits
of base pair information only hundred and fifty thousand base
(25:55):
pairs a GOO. This was super complicated because, like I said,
you know, we have identified genes and figured out what
some genes do and what you know, what they're encoded
to do, what kind of proteins there they make. But
there's a lot of replicated information within human genes. There
there are a whole segments that you look at, Like
(26:16):
when I made that talk about the magnetic tape, it's
as if like let's say that we're talking about magnet
tape and it's an old cassette tape that has music
on it. It would be like you're listening to an
album and three songs after the first song, like, you
listen the first song like that's pretty good. Three more
songs go by, and then the first song comes on again,
like why did they do it twice? The human gene
genome is kind of filled with stuff like that, including
(26:39):
stuff that we still call non coding DNA because we
don't know if it actually is doing anything all right,
So they had to they had to split up the
total genome into these kind of workable fragments. They split
it further than I just mentioned, know what's called subclones,
and then let these bacteria replicate these little pieces of
DNA and in a way that they can really get
in and figure out what the pairs are doing and
(27:01):
and and how everything fits together. So they wind up
with a with A, B, A C library and and
from that, you know, have have determined the sequences of
the chemical base pairs that make up DNA and have
put all of this information into databases for researchers to
play around with. Yeah, it's also interesting to me that
(27:22):
early on, when they were first identifying genes, it was
at such a slow pace relatively speaking, that there were
people who thought that it was going to take a
century to map out the human genome. The projected timeline
for the project was from two thousand and five. They
completed it two years early in two thousand three, and
(27:42):
um about point three billion under budget. So and that
was so part of it is because they could not
anticipate improvements in the processes. I mean, we we never can, right.
We never think in ten years we'll be able to
do this much more quickly because of X. We usually
think in terms of what we're capable of doing right now,
(28:05):
and that's how we project out how long it's going
to take us. If we're lucky, then technology and science
progresses at such a rate that the task becomes less overwhelming. Also,
we learned that it wasn't as big a job as
we as we original thought. Yeah, well it's um, you know,
intracellular biology progressed and really dovetailed with the computer industry,
(28:27):
and if we had not had the kind of developments
and computers, then shortly we've taken Yeah, that's what I
was just thinking of starting in the early nineties. I mean,
think of how crappy computers were back then. But another
interesting thing, mine still ran on a O L that's
not how that so another wow, it was like a
(28:49):
thousand people cried out in anguish. I'm imagining that they're
doing the Human Genome project with like the desktop calculator
application and Windows three point one. Well, you know what's
also interesting is that this is not directly related to
the Human Genome project, but it's it's a similar field. Uh.
You know, I was talking about proteins earlier, these long
(29:10):
chains of amino acids. One of the other interesting things
about proteins is that they fold, and when they fold,
that's what gives them certain features of property properties exactly,
thank you. And we don't fully understand the folding process. Well,
the folding is determined we think by the amino acid sequence, right,
So it's it's a long chain and you can imagine
(29:31):
that it's like a chain of letters in a particular sequence, right, um,
and what order the letters come in determines the three
dimensional shape that the protein twists up into. Right. And
there's actually a really cool project called Folding at Home.
Have you guys heard of this. Folding at Home is
one of those distributed computing networks where, uh, you can
(29:52):
participate in helping scientists determine what proteins will take, what shapes,
why they do it, what kind of properties they have.
It's really be useful for things like potential medical uses.
So what happens is it's one of those that you
sign up for this project, you install some software, and
then your computer, when it's idle, is actually working on
these various computer models of proteins, and as it solves
(30:16):
these different models, it then sends that information back off
to the centralized server which collects it and you know,
vets everything that comes back in. Keep in mind, this
is all automatic. You're not putting in any even put here,
but it vets it all and then essentially puts it
in a database. So that the body of knowledge about
proteins and how they fold grows dramatically over time as
(30:39):
more and more people joined this project. I love that
kind of distributed simulation. Just that that's steady, right, But anyway,
that's that's getting even further afield. So back to the
human genome. So along with sequencing the human genome, the
project led to UM a lot of other creatures genomes
being sequenced UM like I said earlier, ecal um, mice,
(31:00):
the fruit fly, stuff like that, UM to to help
us start working in the larger gene field. And basically
all of the research that's happening today and in gene
therapy and in genetics is because of the research that
was pioneered in the Human Genome project. I think that's
really useful having the full genomic information about like fruit
(31:22):
flies or icola. I mean, you can run so many
generations of those organisms in the lab, which you can't
do with humans and and probably can't even realistically do.
And and usually the genomes are a lot shorter on
on more simple organisms, which is interesting. It's not always
the case because there are like like the number of
genes you can find in certain creatures can be dramatically
(31:46):
larger than that of UM, or dramatically more than what
you would find in humans. It's the plexity doesn't necessarily translate.
It does not and uh and it depends on I mean, like,
for example, the platypus has ten sex chromosomes. Yeah, it does.
I don't even know what that's for. Only platypus is no.
(32:07):
They have a they have a don't ask, don't quack policy.
Do they know? What do they do? They pretty much
don't do anything. Have you not watched They don't do
very much have some kind of crazy sex. Al Right, guys, guy,
if you know what a platypus, if you know the
platypus sounds like I want to hear it, let me
let me know. Okay, all right, that's fair. So so
(32:27):
the first person who can send us a sound of
a platypus, when's Laurence applause? Yeah, okay. So we've mentioned
some basic research in the abstract, but what can you
actually do with genetic genetic information? Like, how do you
apply it practically? Gosh, Joe, I don't know that was
your segment. I was hoping you'd tell us. So one
(32:49):
of the things we want to talk about was this
idea of DNA matching, right, the idea of being able
to to I mean, think about if you are able
to understand your genetic information, if you're able to know
that this sequence is something that was inherited, then that
means that you can find links between you and other people.
It means that it could be useful for things like
(33:11):
a genealogy. It can be useful for things like paternity testing.
It can be useful for things like someone left some
blood behind at this crime scene. I wonder whose blood
this is. There are a lot of different potentials. Yeah.
So one of the interesting things I was thinking about
was was paternity testing, and I wondered, how did they
(33:34):
do this before they had genetic testing, and then furthermore,
just how does it actually work? But it so, one
of the things I found that I thought was interesting
was before they had genetic paternity tests, they would often
use blood type testing. Okay, that makes you know enough sense,
I suppose. I mean, it's it's pretty inaccurate considering the
(33:56):
number of humans that are out there with similar blood types. Yeah,
they didn't have a lot to work with. But so
with blood testing, so you have a scheme of blood typing,
and they're actually different types of blood typing. There's not
just one type of Uh. One thing you can look
at is like the A B O antigens, right um,
And so that's your system where you can be like
(34:17):
A A B oh um and O positive negative. And
so these things are inherited. But some of these are
dominant and some are recessive. And once we had a
Mendalian genetic model for how blood types A B O
blood types are inherited. You could use that to say, well,
(34:38):
you couldn't identify for sure that somebody was somebody's kid,
but you could rule out that they could be their kid. Right,
so someone narrowed down the field. Well, one thing I
read about it apparently this happened to Charlie Chaplin. Like
somebody said that Charlie Chaplin had had fathered her child
and he denied it. And uh, and the genetic not genetic.
(35:01):
It was before genetic testing that the blood type testing
said that he was not the father um in a
very more Povich kind of way. But but apparently they
couldn't use this in the courts at that time, and
so he ended up paying child support anyway. So, so
tell me about the the progression from this fairly primitive
(35:23):
in the grand scheme of things approach to matching to
DNA matching. Well, now that we've got d N A,
we've got a much higher uh, we've got more things
to match, basically to give you a stronger piece of confidence.
So let's say that your blood type test only shows agreement. Well,
(35:44):
that doesn't narrow it down much at all, like we
talked about. But let's say you can identify a certain
number of genetic markers between the suspected father and the
child and look for matches. Now, if you only have
a suspected father and the child, it's a little bit
harder to get a positive match, um, because you can
(36:06):
look at a child and say, like they say, they
have a gene like A and B, and um, the
father has genes B and C. You don't know if
that be in the child necessarily came from the father. Yeah. Um,
But you can get a much better idea if you
(36:30):
also have the mother's DNA and find that in that
same genetic marker the mother does not have B. So
there you have a much higher level of confidence. You
do this over multiple genetic markers, and if you keep
finding matches between the father and the child that do
not match with the mother's DNA, then you have a
(36:53):
near certainty. Um, the more markers you measure, the higher
certainty you can get. What they don't do, though, is
they don't compare the entire genome, because, as we've talked about,
lots of it just wouldn't make any difference, and and
lots of it would be identical anyway, because it's identical
in everybody. Also, processing all of that would be way
more work than is in any way necessary. Yeah. Well,
(37:16):
in fact, all human beings have it's like ninety nine
point nine percent the same DNA, and right, it'd be
like taking a book that's a thousand pages long, and
nine hundred and ninety nine of those pages are going
to be identical. They kind of the identical words on them.
But if you but there's one page worth of words
that will be different, and you have to go through
(37:37):
the whole thing. They're spread out throughout the entire For
those words are spread out, Yeah, it's it's our Our
code differs it around um ten million points out of
you know, three point two billion. Yeah, that's right. So
it would be like the genetic expertise. What you do
there is you open the book to a certain page
that you already know is going to have a variant
on word number three on this page, and then you
(38:00):
can compare it from there, and then you just do
that as many times as possible on down the line. Now,
of course, once you get a certain number of matches,
it's it's so certain that you really just don't need
to mess with it anymore. Sure that that the odds
of any other person it's a are are just incredibly tiny.
This is from a BBC right up. So forensic DNA
(38:23):
test and this is it's talking about forensic d so
that this isn't a paternity business. Yeah, it would be
a crime. But so to identify a blood sample to
the same person, you'd examine like six to ten genetic
markers and they say the chances of two unrelated people
having the same matches in those cases is one and
(38:43):
one billion. Those are those are some pretty high odds there, um.
And of course, so that brings up the other thing.
Genetic matching is often often also used in forensic analysis,
so you can use it in the court system to
try to prove somebody guilt. And I know that this
is difficult in a lot of cases because there's frustration
(39:06):
that I think both sides in court cases have the
juries don't really understand DNA evidence in a lot of cases,
and they value they can value eyewitness testimony above DNA evidence.
I mean, there are plenty of cases where either someone
was pronounced guilty or not guilty, and there have been
(39:26):
a lot of there's been a lot of criticism in
in cases all across the board where it seemed like
a jury was ignoring any sort of DNA evidence in
favor of eyewitness testimony. And one of the things we
can tell you a lot about is that human memory
is not infallible. You can't. You can't just think that
(39:47):
human memory is perfect. And even if someone is being
completely honest when they're on the stand, they could be
telling that doesn't mean that they're not wrong. Yeah, they
could be telling something that's totally wrong. It's essentially a falsehood,
but it's not one that they intended to be false.
It's just that they remember it differently than how it
actually happened. Whereas DNA testing, assuming everything is on the
(40:07):
up and up right, assuming there's no tampering, assuming that
everyone was following proper procedure and proper controls, is far
more reliable. But that's not generally understood. Yeah, I mean,
if you have a reputable lab doing this, and especially
if you get redundant results from multiple labs and they're
testing a large number of markers, it's going to be right,
(40:31):
you know. Yeah, again, unless you're identical twin committed the crime,
or or unless unless you've been framed. Yeah, right right,
that's that's the other that's the only other real option.
So identical twins are not always genetically identical. That's yeah,
that's true. Interesting point. Yeah, it's it's those you know
that that you know, ten million different differentiation points are
(40:54):
can be can be different. I think monos I gottic
twins are. They're sort of generally con sidered genetically identical.
But is it a case where what there is variation
but there's so little variation it's negligible, or or what's
the deal. Well, there's um those differences that I was
talking about are called single nucleotide polymorphisms, and and so
(41:17):
few of them can be different. But you know that
that for for all phenotype, all visual intents and purposes
to people would be identical. But but for example, some
some identical twins are more likely to get certain mental
health issues or physical issues like one over the other. Yeah,
so one might could that could that also be influenced
(41:40):
by environmental factors like causing genetic changes? Oh yeah, you know,
our genes definitely can undergo changes that aren't you know.
It's not like when you inherit your genes that that's
the way they are for the rest of your life.
They can change and do change due to lots of
different factors, including environmental factors. Uh. That's that's whole the
(42:00):
process of mutation, which we will cover in depth in
another episode. Join us next time when we talk about
gene therapy and x men. Yeah, that's right, that's coming
up in the next episode. We're really excited to talk
about it. So you guys have to wait a couple
of days, but we get to wait all of you know,
a couple of minutes. So we're gonna wrap this up. Guys.
If you have any suggestions for future episodes of Forward Thinking,
(42:21):
go to f W thinking dot com. That's where we've
got all the podcast blog posts, we've got links to
other articles. You can get in touch with us through there,
and we are excited to hear from you and for
you to be come fart of this conversation about the
future and what's gonna be awesome about it, and we
will talk to you again really soon. For more on
(42:44):
this topic in the future of technology, visit forward thinking
dot Com, brought to you by Toyota to go places
Fw:Thinking News
Hosts And Creators
Jonathan Strickland
Joe McCormick
Lauren Vogelbaum
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