Download Evolution and Differentiation

Nature’s Monte Carlo Bakery:
The Story of Life as a Complex System
GEK1530
Frederick H. Willeboordse
[email protected]
1
Evolution and Differentiation
Lecture 9
Life started with some form of
simple (single)-cellular organism.
What are the mechanisms by
which this organism evolved and
how do cells differentiate.
2
GEK1530
Evolution
Overview - Major Transitions
Before we investigate the details a bit more, let us have
a look at the bigger picture.
Reproducing Protocells
Replicating Cells
Prokaryotes
Eukaryotes
Multi-cellular organisms
Sexual reproduction
3
GEK1530
Fossilisation
The oldest fossils (about 3.5Gya)
are found in a fine grained quartz
called “chert”.
Typical Chert
Quartz has the chemical formula SiO2 (same as glass). Fossilbearing cherts are made up of tiny interlocking grains of quartz
laid down from solution.
The precipitated grains took thousands of years to solidify. As
the sedimentary rock formed, the dead microbes trapped in the
sediment were petrified, that is turned into stone.
4
GEK1530
Fossilisation
The tiny quartz grains (forming inside & around the microbes
on all sides) developed so slowly that they grew through the cell
walls instead of crushing them.
As a result, these fossils are preserved in three dimensions as
unflattened bodies.
They have quartz-filled interiors & brownish color due to the
decomposed organic matter of the cell. The fossils found in
cherts resemble present-day microbes.
5
GEK1530
Earliest Known Fossils
3,465±5Gyo
Interpretative
drawing
6
GEK1530
Earliest Known Fossils
Fossils are
inside this grain
7
GEK1530
Earliest Known Fossils
8
GEK1530
Earliest Known Fossils
Importance of Apex chert fossils
Taxonometry:
Implies close relationship to modern cyanobacteria.
Implies life was flourishing on earth 3.5 Gya, just 200 to 500My
after the earth became habitable.
Conclusions:
The 3.5Gyo fossils are remains of water borne microbes with
the following properties.
•
•
•
•
prokaryotes
phototrophs,
oxygen producers
cyanobacterium-like
9
GEK1530
Evolution
Reproduction - Replication
It is important to keep in mind that reproduction and replication
are not the same in this context.
Reproduction:
Rough copies are produced, there
is no genetic apparatus.
Replication:
Accurate copies are produced,
there is some kind of a genetic
apparatus.
10
GEK1530
Evolution
Error & Mutation Rates
Whether it be reproduction or replication, error and mutation rates
play an essential role.
Most probably, systems that merely reproduce are significantly
more error tolerant.
Low error/mutation rates would seem to
be good. However, in order for evolution
to proceed, some changes and hence
errors/mutations are necessary.
11
GEK1530
Evolution
New Genes
New genes do not appear out of nowhere through spontaneous
random combinations of nucleotides. At least no such mechanism
is known to exist.
New genes are based on existing genes.
12
GEK1530
Evolution
New Genes
Some genes are more ‘open’ to change than others.
This can be understood in the following way:
Firstly, we need to consider that there are roughly
three types of mutations:
Mutations that cause serious
damage.
Such mutations will generally
lead to the death of the organism
and hence not be passed on to
future generations.
Mutations that are beneficial.
These will be passed on to
future generations and increase
the likelihood its genome will
survive.
Mutations that make no/little
difference in the functioning of
the organism.
These will be passed on to
future generations but no help in
its survivability.
13
GEK1530
Evolution
New Genes
Secondly, we need to consider that not all genes are equally
important:
Redundant segment.
Here changes may continue.
Non-essential segment.
Changes may or may not work
out.
Highly optimized, essential
segment.
Since such an element is
highly optimized, the chance
of obtaining an even better
optimization are extremely
small. Changes are most likely
to be damaging. Due to the
essential nature of the
segment, the organism will
likely die.
14
GEK1530
Evolution
New Genes
Consequently:
Some ribosomal RNA, e.g., has hardly changed since the first
modern cells evolved.
This is because the process of translation is absolutely essential
for all such cells. And since this process applies to many different
types of genes, any error in the ‘translator’ will likely break many
functions.
This is very helpful when constructing a tree of life.
15
GEK1530
Evolution
New Genes
There are four basic ways to obtain new genes
from existing genes:
Old Gene
New Gene
Old Organisms
New Organisms
Intragenic mutation
Gene Duplication
DNA Segment Shuffling
Horizontal Transfer
16
GEK1530
Stages
Cellular Stage - DNA
The division of labor between RNA, DNA and proteins.
This led to the common ancestor of
all living modern cells which can
be classified as belonging to one of
three different domains:
Archaea
Eubacteria
Prokaryotes
Eukaryotes
17
GEK1530
Stages
Symbiosis
Lynn Margulis
•
•
Most active promoter of the idea that symbiosis played a key
role in the evolution of life.
There is plentiful evidence that parts of eukaryotic cells were
originally independent organisms (Mitochondrion,
Chloroplast).
18
GEK1530
Stages
Cellular Stage - Prokaryotes
All parts (DNA, RNA, proteins etc) in one compartment
– i.e. no nucleus.
Single cellular - greatest biochemical diversity
Mostly about 1,000 – 4,000 genes.
Natural Selection seems to favor the cells that can reproduce the
fastest. Hence the fewer nucleotides to copy the better.
Consequently, the genomes are usually compact and efficient.
Horizontal transfer of genes is relatively common (even among
prokaryotes of different species).
19
GEK1530
Stages
Prokaryotes - Archaea
A fairly recent discovery!
Initially found in what we would consider inhospitable
environment but now known to be quite widespread
Thermophiles
Halophiles
20
GEK1530
Stages
Prokaryotes – Eubacteria
Phototrophic
Lithotrophic
Organotrophic
21
GEK1530
Stages
Cellular Stage – Eukaryotes
Eukaryotic cells are generally bigger (often 10 times in length
and 1000 times in volume) and more complex than prokaryotic
cells. Their genome is usually larger as well.
The genome is stored in a separate nucleus.
There are organelles (mitochondira/chloroplasts) with their own
DNA.
Horizontal transfer of genes rather uncommon.
22
GEK1530
Stages
Cellular Stage – Eukaryotes
23
GEK1530
Stages
Eukaryotes - Kingdoms
There are four kingdoms
Protists
Fungi
Single-cellular
Plants
Animals
Multi-cellular
24
GEK1530
Stages
Eukaryotes - Protists
These are single cellular eukaryotes. Even so, they can be very
complex.
Protozoa
Hunters
Yeasts
Algae
Scavengers
Photo-synthesizers
25
GEK1530
Stages
Sideline: Horizontal Transfer
Perhaps, horizontal transfer was very common among primordial
cells.
This may explain why eukaryotes
are similar to archaea in DNA
replication and transcription but
similar to eubacteria in metabolism.
If eukaryotes, archaea and
eubacteria would have branched off
a tree, this relationship would be
rather unlikely.
Archaea
Eubacteria
Eukayotes
26
GEK1530
Stages
Cell Differentiation
Plants
Appeared about 500 million
years ago.
Animals
Unclear when they first
appeared. However, the first
vertebrae lived around 540
million years ago.
27
GEK1530
Cell Differentiation
The jump from single-cellular life to multi-cellular life is far
from trivial! Even so, it appears to have happened 3 times in
evolutionary history.
Animals
Single-Cellular Life
Eukaryote
Plants
Fungi
This may have happened about 1 billion years ago
28
GEK1530
Cell Differentiation
Or may be it was trivial (this is still unknown) and simply a
dynamical response to a changing environment.
A key issue here is the
level of Oxygen.
Obviously, larger organisms need more Oxygen and hence a
way to transport that Oxygen to where it is needed.
If the concentration of Oxygen is low it is hard to see how
compact multi-cellular life can exist since only a few cells will
need to absorb the Oxygen for other cells (and this means per
definition that those few cells will need to absorb more than an
individual cell would).
29
GEK1530
Cell Differentiation
There is some indication that early multi-cellular life was very
thin so that Oxygen could directly diffuse into the cells (this also
makes sense since it would take time for blood vessel-like
systems to evolve).
In any case, cell differentiation did happen.
So what are its mechanisms?
Adult human: 1013 cells and ~ 200 cell types.
30
GEK1530
Cell Differentiation
Clearly, the cells in multi-cellular organisms not only fulfill
different roles but they are also physically different.
Different Role
Neuron
Different Physically
Hart Muscle
Differentiated Cell
From a dynamical systems point of view the above distinction is
far from trivial. In computers for example, programs with
different roles may still use all the same hardware.
31
GEK1530
Cell Differentiation
If the Cells are physically different, how does this difference
come about?
There are two main options one could think about:
Parent Cell
Daughter Cell receives only the
genes required
Daughter Cell receives all the genes
but only some are active
It turns out that the 2nd option is what happens.
32
GEK1530
Cell Differentiation
Although clear evidence needs genetic analysis, it is nevertheless
possible to at least suspect that this is correct from daily
experience.
Cut off tip
Plant shoot
Grows roots!
This is only possible if somehow the tip contains the information
for making roots.
33
GEK1530
Cell Differentiation
If the DNA of virtually all the cells in a multi-cellular organism
is identical then we have to ask:
Identical DNA
How can it fulfill different roles?
How can it lead to different
physical properties?
In a simple (but wrong) computer analogy, one could surmise
that there’s a gene for everything as there are subsystems and
subroutines for everything in a computer.
34
GEK1530
Cell Differentiation
The idea of a gene for everything is untenable, however, since
the human genome only contains around 30,000 genes.
Since it is also known that DNA by itself is
static (it can make nice crystals for example)
it seems more likely that:
DNA Crystal
We can look at the cell as a dynamical system where the DNA
interacts with its environment and thus reaches certain stable
states.
If such a picture is correct, it would fit
very nicely with the idea of life as a
complex system.
35
GEK1530
Cell Differentiation
But what determines the Cell state?
It had generally been assumed that genome and environmental
state determine the cell state but this turned out to be incorrect
however (at least as a generic truth).
This can be seen by an experiment with E. coli bacteria.
Many people believe(d) that, due to their relative simplicity, the
idea of the cell state being determined by the genome and the
environment would be true for bacteria.
It was found by Ko & Yomo in 1994, however, that even when
starting from a single bacterium (assuring identical genomes)
resulting colonies could display large variations in enzyme
activity.
36
GEK1530
Cell Differentiation
They discovered that several switching types occur between cells
with low and high enzyme activities.
Low
Low
High
Low
High
Low
High
Furthermore this switching could affect either all of the cells of a
colony or only some.
Consequently, cell state is not necessarily determined by genome
and environment only.
37
GEK1530
Cell Differentiation
The changes in cell state occur spontaneously as they may in a
system with chaotic dynamics.
Of course, in multi-cellular organisms, cells do not spontaneously change their activity levels in the sense as above but what this
experiment provides us with is additional support for viewing the
cell as a non-linear dynamical system.
If (virtually) all the cells have the same genes, how are they
activated?
There are regulator genes that can turn other genes on or off.
Interestingly, these regulator genes themselves can be turned on
or off depending on the presence/absence of inhibitors.
38
GEK1530
Cell Differentiation
Consequently, we have a stunning mechanism where:
In principle, any chemical can
switch on/off any gene!
What is noteworthy is that this
regulating mechanism already exists
in prokaryotes ( )and hence
predates multi-cellular life.
39
GEK1530
Cell Differentiation
Heredity
Thus far it was mentioned that when cells divide, the genes are
copied.
They then differentiate on the basis of the environment and some
internal dynamical state.
But there’s one more issue:
When one cultures regular cells like fibroblasts, they will remain
fibroblasts even when they divide.
40
GEK1530
Cell Differentiation
Heredity
Hence, there also must be a mechanism for transferring the
current state of a cell to a daughter cell.
This is achieved by a labeling system where
markers are attached to genes.
Interestingly enough, this system too exists in prokaryotes.
41
GEK1530
Cell Differentiation
Heredity
Hence there is a dual system for heredity.
Copying of genes
Copying of cell state
And there’s a mechanism for switching genes on/off.
Both these are essential for multi-cellular life in order to allow
for cell differentiation and both already exist in prokaryotes.
Hence, the evolution of multi-cellular life is perhaps not such a
big modification after all.
42
GEK1530
Cell Differentiation
Response
Gene expression is not solely derived from the parent cell
though.
Gene expression can change as a
response to external inputs.
Such change can be quite radical (like in cloning) but usually
changes are relatively limited (a kidney cell e.g. will not turn into
a neuron … )
First of all it is important to note
that many processes are common
to all cells e.g.
Structural proteins of
chromosomes
RNA polymerases
DNA repair enzymes
Ribosomal Proteins
…
43
GEK1530
Cell Differentiation
How different?
Secondly, it is important to note that there are at least 6 main
stages where gene expression can be controlled.
Transcriptional control
RNA processing control
RNA transport and localization control
Translation control
mRNA degradation control
Protein activity control
Inside Nucleus
Inside Cytosol
Hence there is clearly a cascading effect
Many of the bigger differences may be explained
by the accumulation of smaller differences.
44
GEK1530
Wrapping up
Give it some thought
Key Points of the Day
Is cell differentiation is like moving
towards various chaotic attractors?
No life without
information!
References
http://www.museum.vic.gov.au/prehistoric/what/eras.html
http://www.xenbase.org/
http://www.ucmp.berkeley.edu/
Stephen J. Gould
M. Philpott
The Cell, Alberts et al
4th edition
45