Lectures by

John F. Allen

School of Biological and Chemical Sciences, Queen Mary, University of London

Cell Biology and Developmental Genetics

1jfallen.org

Cell Biology and Developmental Genetics

Lectures by John F. Allen

Endosymbiosis and the origin of bioenergetic organelles. Some history

Endosymbiosis and the origin of bioenergetic organelles. A modern view

Mitochondria as we know them and don't know them

Why do chloroplasts and mitochondria have genomes?

Co-location for Redox Regulation

Mitochondria, ageing, and sex – energy versus fidelity

Cell Biology and Developmental Genetics

Lectures by John F. Allen

Slides and supplementary information:

jfallen.org/lectures

School of Biological and Chemical Sciences Seminars

WEDNESDAYS AT 12 NOON IN G23, G. E. FOGG BUILDING

3 February 2010

Dr Nick LaneProvost’s Venture Research Fellow, University College LondonLife Ascending. The Ten Great Inventions of Evolution

Lecture 4

Why do chloroplasts and mitochondria have genomes?

I II III IV ATPase

Mitochondrial matrix

Inter-membrane space

Chloroplast stroma

Thylakoid lumen

Cyt b6-f Photosystem I ATPasePhotosystem II

RubisCO

Problem

Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?

Why do mitochondria and chloroplasts require their own separate genetic systems when other organelles that share the same cytoplasm, such as peroxisomes

and lysosomes, do not? …. The reason for such a costly arrangement is not clear, and the hope that

the nucleotide sequences of mitochondrial and chloroplast genomes would provide the answer has proved unfounded. We cannot think of compelling

reasons why the proteins made in mitochondria and chloroplasts should be made there rather than in the

cytosol.Molecular Biology of the Cell

© 1994 Bruce Alberts, Dennis Bray, Julian Lewis, Martin Raff, Keith Roberts, and James D. WatsonMolecular Biology of the Cell, 3rd edn. Garland Publishing

Proposed solutions (hypotheses)

There is no reason. “That’s just how it is”. (Anon)

The “Lock-in” hypothesis. (Bogorad, 1975). In order for core components of multisubunit complexes to be synthesised, de novo, in the correct

compartment.

The evolutionary process of transfer of genes from organelle to nucleus is still incomplete.

E.g. Herrmann and Westhoff, 2001: The partite plant genome is not in a phylogenetic equilibrium. All available data suggest that the ultimate aim of genome restructuring in the plant cell, as in the eukaryotic cell in general,

is the elimination of genome compartmentation while retaining physiological compartmentation.

The frozen accident. The evolutionary process of gene transfer was underway when something happened that stopped it. E.g. von Heijne,

1986.

It’s all a question of hydrophobicity. The five-helix rule. (Anon)

Some proteins (with co-factors) cannot be imported. (Anon)

Co-location for Redox Regulation - CoRR (Allen 1993, 2003 et seq.)

Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?

Proposed solution (hypothesis)

Why Mitochondria and Chloroplasts Have Their Own Genetic Systems

Allen, J. F. (1993) J. Theor. Biol. 165, 609-631

Allen, J. F. (2003) Phil. Trans. R. Soc. B458, 19-38

Co-location for Redox Regulation - CORR

Vectorial electron and proton transfer exerts regulatory control over expression of genes encoding proteins directly

involved in, or affecting, redox poise.

This regulatory coupling requires co-location of such genes with their gene products; is indispensable; and operated

continuously throughout the transition from prokaryote to eukaryotic organelle.

Organelles “make their own decisions” on the basis of environmental changes affecting redox state.

BacteriumEndosymbiontBioenergetic organelle

1. As now generally agreed, bioenergetic organelles evolved from free-living bacteria. 2. Gene transfer between the symbiont or organelle and the nucleus may occur in

either direction and is not selective for particular genes.3. There is no barrier to the successful import of any precursor protein, nor to its

processing and assembly into a functional, mature form. 4. Direct redox control of expression of certain genes was present in the bacterial

progenitors of chloroplasts and mitochondria, and was vital for cell function before, during, and after the transition from bacterium to organelle. The mechanisms of this control have been conserved.

5. For each gene under redox control, it is selectively advantageous for that gene to be retained and expressed only within the organelle.

6. For each bacterial gene that survives and is not under redox control, it is selectively advantageous for that gene to be located in the nucleus and expressed only in the nucleus and cytosol. If the mature gene product functions in chloroplasts or mitochondria, the gene is first expressed in the form of a precursor for import.

7. For any species, the distribution of genes between organelle and nucleus is the result of selective forces that continue to operate.

8. Those genes for which redox control is always vital to cell function have gene products involved in, or closely connected with, primary electron transfer. These genes are always contained within the organelle.

9. Genes whose products contribute to the organelle genetic system itself, or whose products are associated with secondary events in energy transduction, may be contained in the organelle in one group of organisms, but not in another.

10. Components of the redox-signalling pathways upon which co-location for redox regulation depends are themselves not involved in primary electron transfer, and so their genes have been relocated to the nucleus.

Co-location for Redox Regulation - CoRRTen assumptions, axioms, principles jfallen.org/corr

Co-location for Redox Regulation - CoRR

Prediction: Explanation of previous knowledge

Distribution of genes for components of oxidative phosphorylation between mitochondria

and the cell nucleus

Prediction: Experimental results

Redox control of mitochondrial and chloroplast gene expression

Prediction: Experimental results

Persistence of “bacterial” redox signalling components in chloroplasts and mitochondria

Co-location for Redox Regulation - CoRR

Prediction

Explanation of previous knowledge

Distribution of genes for components of oxidative phosphorylation between mitochondria and the cell nucleus

Redox regulation

Redox regulation

Nucleus Cytosol

N-phaseMitochondrial matrix

O2

H2O

I II III IV ATPase

Mitochondrial matrix

Inter-membrane space

I II III IV ATPase

Mitochondrial matrix

Inter-membrane space

H+ H+ H+

H+

NADH O2

ATP

ADP

H2O

NAD+ succinate fumarate

Redox regulation

Nucleus Cytosol

N-phaseMitochondrial matrix

O2

H2O

Allen JF (2003) The function of genomes in bioenergetic organellesPhilosophical Transactions of the Royal Society of London Series B-Biological Sciences 358: 19-37

Co-location for Redox Regulation - CORR

Prediction

Explanation of previous knowledge

Distribution of genes for components of photosynthetic phosphorylation between

chloroplasts and the cell nucleus

Redox regulation

Redox regulation

Light Light

Nucleus Cytosol

N-phaseChloroplast stroma

CO2

CH2O

Chloroplast stroma

Thylakoid lumen

Cyt b6-f Photosystem I ATPasePhotosystem II

RubisCO

Cyt b6-f Photosystem I ATPase

Chloroplast stroma

Thylakoid lumen

Photosystem II

RubisCO

H+H+ H+

H+

ATP

NADP+

O2

H2O

H+

H+

H+

ADP

NADPH

ATP

ADP

H2O O2

NADP+

NADPH

Redox regulation

Light Light

Nucleus Cytosol

N-phaseChloroplast stroma

CO2

CH2O

Allen JF (2003) The function of genomes in bioenergetic organellesPhilosophical Transactions of the Royal Society of London Series B-Biological Sciences 358: 19-37

Co-location for Redox Regulation - CoRR

Prediction: Explanation of previous knowledge

Distribution of genes for components of oxidative phosphorylation between mitochondria

and the cell nucleus

Prediction: Experimental results

Redox control of mitochondrial and chloroplast gene expression

Prediction: Experimental results

Persistence of “bacterial” redox signalling components in chloroplasts and mitochondria

Lecture 5

Co-location for Redox Regulation