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GEK1530Frederick H. Willeboordsefrederik@chaos.nus.edu.sg

Nature’s Monte Carlo Bakery:The Story of Life as a Complex System

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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.

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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

Evolution

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The oldest fossils (about 3.5Gya) are found in a fine grained quartz called “chert”.

Fossilisation

Quartz has the chemical formula SiO2 (same as glass). Fossil-bearing 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.

Typical Chert

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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.

Fossilisation

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Interpretative drawing

3,465±5Gyo

Earliest Known Fossils

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Fossils are inside this grain

Earliest Known Fossils

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Earliest Known Fossils

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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.

Earliest Known Fossils

• prokaryotes• phototrophs, • oxygen producers• cyanobacterium-like

Importance of Apex chert fossils

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Reproduction - Replication

It is important to keep in mind that reproduction and replication are not the same in this context.

Reproduction:

Replication:

Rough copies are produced, there is no genetic apparatus.

Accurate copies are produced, there is some kind of a genetic apparatus.

Evolution

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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.

Evolution

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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.

Evolution

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New Genes

This can be understood in the following way:

Firstly, we need to consider that there are roughlythree 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 make no/little difference in the functioning of the organism.These will be passed on to future generations but no help in its survivability.

Mutations that are beneficial.These will be passed on to future generations and increase the likelihood its genome will survive.

Some genes are more ‘open’ to change than others.

Evolution

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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.

Evolution

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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.

Evolution

New Genes

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There are four basic ways to obtain new genes from existing genes:

Intragenic mutationOld Gene New Gene

Gene Duplication

DNA Segment Shuffling

Horizontal Transfer

Old Organisms New Organisms

Evolution

New Genes

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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:

ArchaeaEubacteria

EukaryotesProkaryotes

Stages

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Lynn MargulisSymbiosis

• 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).

Stages

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Cellular Stage - Prokaryotes

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.

All parts (DNA, RNA, proteins etc) in one compartment – i.e. no nucleus.

Horizontal transfer of genes is relatively common (even among prokaryotes of different species).

Single cellular - greatest biochemical diversity

Stages

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Prokaryotes - Archaea

A fairly recent discovery!

Initially found in what we would consider inhospitable environment but now known to be quite widespread

Thermophiles Halophiles

Stages

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Prokaryotes – Eubacteria

Organotrophic

Phototrophic

Lithotrophic

Stages

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Cellular Stage – Eukaryotes

Horizontal transfer of genes rather uncommon.

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.

Stages

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Cellular Stage – Eukaryotes

Stages

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Eukaryotes - Kingdoms

There are four kingdoms

PlantsProtists AnimalsFungi

Multi-cellularSingle-cellular

Stages

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Eukaryotes - Protists

These are single cellular eukaryotes. Even so, they can be very complex.

ProtozoaHunters

AlgaePhoto-synthesizers

YeastsScavengers

Stages

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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

Stages

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Cell Differentiation

Plants

Animals

Appeared about 500 million years ago.

Unclear when they first appeared. However, the first vertebrae lived around 540 million years ago.

Stages

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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.

Single-Cellular Life

Animals

Plants

Eukaryote Fungi

This may have happened about 1 billion years ago

Cell Differentiation

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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).

Cell Differentiation

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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).

Cell Differentiation

In any case, cell differentiation did happen.

So what are its mechanisms?

Adult human: 1013 cells and ~ 200 cell types.

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Clearly, the cells in multi-cellular organisms not only fulfill different roles but they are also physically different.

Differentiated Cell

Different Role

Different Physically

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.

Neuron

Hart Muscle

Cell Differentiation

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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.

Cell Differentiation

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Although clear evidence needs genetic analysis, it is nevertheless possible to at least suspect that this is correct from daily experience.

Plant shoot

Cut off tip

Grows roots!

This is only possible if somehow the tip contains the information for making roots.

Cell Differentiation

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If the DNA of virtually all the cells in a multi-cellular organism is identical then we have to ask:

Identical DNAHow can it fulfill different roles?

How can it lead to differentphysical 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.

Cell Differentiation

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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:

We can look at the cell as a dynamical system where the DNA interacts with its environment and thus reaches certain stable states.

DNA Crystal

Cell Differentiation

If such a picture is correct, it would fit very nicely with the idea of life as a complex system.

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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.

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).

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They discovered that several switching types occur between cells with low and high enzyme activities.

Furthermore this switching could affect either all of the cells of a colony or only some.

Low High High Low

Low HighLow

Cell Differentiation

Consequently, cell state is not necessarily determined by genome and environment only.

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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 spontaneous-ly 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.

Cell Differentiation

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.

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What is noteworthy is that this regulating mechanism already exists in prokaryotes ( )and hence predates multi-cellular life.

Consequently, we have a stunning mechanism where:

In principle, any chemical can switch on/off any gene!

Cell Differentiation

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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.

Heredity

Cell Differentiation

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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.

Heredity

Cell Differentiation

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Hence there is a dual system for heredity.

Copying of genes

And there’s a mechanism for switching genes on/off.

Copying of cell state

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.

Heredity

Cell Differentiation

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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 … )

Response

Cell Differentiation

First of all it is important to note that many processes are common to all cells e.g.

Structural proteins of chromosomesRNA polymerasesDNA repair enzymesRibosomal Proteins…

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Secondly, it is important to note that there are at least 6 main stages where gene expression can be controlled.

Transcriptional controlRNA processing controlRNA transport and localization controlTranslation controlmRNA degradation controlProtein activity control

Inside Nucleus

Inside Cytosol

How different?

Cell Differentiation

Hence there is clearly a cascading effect

Many of the bigger differences may be explained by the accumulation of smaller differences.

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Wrapping up

Give it some thought

References

The Cell, Alberts et al4th editionhttp://www.ucmp.berkeley.edu/

Stephen J. Gould

http://www.xenbase.org/

http://www.museum.vic.gov.au/prehistoric/what/eras.htmlM. Philpott

Is cell differentiation is like moving towards various chaotic attractors?

Key Points of the Day

No life without information!