Lecture 1: DNA & Chromosomes
Slide 2 - That DNA in the background of doing its job as template to make
RNA is actually being replicated & associated with that replication is
going to be some sort of organization with the DNA – how the genome
is organized (all the genes in your body).
- Associated with that & the process that is going to be necessary in
order to get that DNA to actually make that RNA, there is going to have
to be some regulation there. When we arrive at that regulation, going to
generate not just all RNA molecules but a subset of them & that’s
known as the transciptome. The process of translation itself is going to
be regulated to give rise again to subset of molecules/proteins known as
- Proteins don’t exist in isolation – bunch of different proteins
interacting with each other – this is known as the interactome &
working together, going to generate the diversity of metabolic processes
that take place in your cells – the metabolome.
- There is going to be cross-talk & inter-regulation b/w all of these –
central dogma looks very complex now – better reflection of the
amazing things that are going on in our cells. Together they give rise to
the people we are right now – what geneticists call the phenotype or in
grand terms what we call the phenome.
- Not only do we make all these things, but we also have to get rid of
them as well.
Slide 4 – Lecture Outline st
Genome - 1 part of central dogma: DNA.
Genome: full complement of genes in an organism.
Slide 5 – Genome sequencing **Don’t need to know the specifics of dates – Want us to know the
generality of when things occur though**
- 1st eukaryotic genome: yeast Saccharomyces cerivisiae – getting
larger (12 Mbp) – started to see then building up an idea what made an
organism – what was the set of instructions that DNA that was found in
each organism, that entire complement of genes that are there.
- 1 animal genome: nematode worm.
- 1 plant genome: model plant Arabidopsis thaliana – model plant is an
organism that one uses to better understand the biology overall of a
particular group of organisms.
- Getting feeling now for how many genes are necessary to give rise to
the organismal diversity that we see in front of us every day.
- 1 mammalian genome was the mouse.
- Gives you impression of the timeline of what we know about genome
– about the info being collected, growing at an ever increasing rate.
Slide 6 – Sequenced genomes - Diversity of genome sequences start to give us a better feeling for what
is going on in terms of the genes that are necessary to give rise to
Slide 7 - This gives us the feeling of ste rate of which genome sequencing is
increasing since ’95 when 1 genome was published (Haemophilus
influenzae genome) until last year 2007 you can see a logarithmic
increase in the amount of genome sequencing that’s been done such that
now greater than 600 genomes since 1995.
- Where it used to take weeks to sequence things, now it takes days to
sequence whole genomes. As a consequence of that, we’re able to enter the so-called the personal genome era.
Slide 8 - Personal genome era is a time frame where we’re actually able to
acquire genome sequences for individuals on demand. The 1 of those
was published last year – the 1 complete genome sequence of a given
individual/known individual was J. Craig Venter – his genome sequence
was published last year.
- Another individual whose genome was sequenced last year – looking
at diversity of genes that he has in his genome & what they tell or what
they might predict about what kind of individual someone like James
Watson is – what sort of maladies/illnesses he may be susceptible for.
- There are companies predicting in the course of the next 5 years
sequencing individual genomes for b/w 1 & 10 thousand dollars.
- This has provided us with an incredible depth of info about the basic
building blocks for organisms – set of programs of algorithms that one
needs to use to build the individuals.
Slide 9 - The personal genome era is going to be to relate all of this info to
biology – how do we relate what we know about whole genomes to
what goes on so you get the phenomes that you see around you?
Slide 11 Nucleoid
**Don’t need to know the names of the small proteins**
Supercoiling of DNA by (class of enzymes) topoisomerases – proteins
that, in energy-dependent fashion, twist the DNA, sometimes actually
inducing single-stranded breaks & then rejoins, depending on the class
of proteins involved, so that you allow the twisting to occur (to scrunch
that up 1000 fold).
- In order to get a bacterial genome inside a bacterial cell, you just need
to condense it a thousand times – need to take something long & linear
(in this case, something circular) & scrunch it up so it’s 1000 times
smaller than it would be than if it was its full size – visage doing this by
taking an elastic band & twisting it – elastic band will get scrunched up
– imagine that occurring at molecular level & that is precisely what
bacteria are doing. The way they accomplish this is by using specific
proteins to do this scrunching – there are proteins that fulfill an
analogous role so together, the DNA & protein form the nucleoid.
- The proteins are positively charged b/c DNA is negatively charged so
if you have positively charged proteins, they’re going to neutralize the
charges & allow you to pack things in close together b/c you won’t have
like charges repelling each other. There are numerous small proteins
then that fulfill this role of neutralizing the charges but also beginning to
do the twisting of the elastic band.
Slide 12 - If DNA was the size of yarn, each cell would have 20 return trips
worth of DNA from Con Hall to City Hall & back.
- Bottom line is: there is an awful lot of DNA in your body that you are
handling moment to moment, minute to minute, every day.