Download presentation
Presentation is loading. Please wait.
Published byGladys Charles Modified over 9 years ago
2
Conceptual foundations for minimal cells Eörs Szathmáry Collegium BudapestEötvös University Budapest
3
Quest for a biological minimal system Chemical supersystem Should be conceptually as simple as possible Must not necessarily be realizable in its simplest form Comparison with other elementary units (such as the elementary cell in crystallography) FORMAL AND EXACT
4
The eukaryotic cell is very complex—too complex! These cells have endosymbiont-derived organelles
5
The simplest cells are bacterial THUS we want to explain the origin of some primitive bacterium-like cell Even present-day bacteria are far too complex The main problem is the genetic code
6
The top-down approach Compare genomes of reduced bacterial cells (such as endosymbiotic parasites) Look for genes that are common to all such genomes Define the intersection of gene sets as the minimal set for prokaryotic organism
7
A problem with the top-down approach Suppose that –Gene a is only in organism A –Gene b is only in organism B –Gene c is common to both From this it DOES NOT follow that you can afford to miss gene a AND b at the same time! Maybe (EITHER a OR b) is ESSENTIAL Compare it with animal locomotion
8
Another problem with the top-down approach Even if you can reduce the set of essential genes to between 200 and 300, it still does include the genes for the genetic code Evolution usually does not solve two diffcult problems at the same time (low probablity x low probability is a very small number!) Origin of life per se and origin of the genetic code should preferably by separated If they cannot be solved sequentially, the situation is hopeless
9
We have to try the bottom-up approach! It must start in chemistry Prebiotic evolution also started in chemistry In vitro construction of minimal cells is an exercise in the design and assembly of chemical supersystems
10
A lot of confusion arises when units of evolution and units of life are taken to be identical The problem of the virus Gánti’s analogy: the virus is the living cells as a self-replicating programme is to the computer Neither the virus nor the programme do not do anything alone
11
Units of evolution (JMS) hereditary traits affecting survival and/or reproduction 1.multiplication 2.heredity 3.variation
12
Units of evolution Units of evolution and units of life viruses memes mules sterilized workers nondividing cells bacteria, protists, etc. Units of life
13
Tibor Gánti Born in 1933 A chemical engineer Patents in industrial biochemistry Syntheses using the controlled operation of enzymatic reaction networks First book on molecular biology in Hungary (1966)
14
The first edition of the Principles A serious book in a popular science disguise (1971) There was no other way to publish Proposal included the term “chemoton” ‘reductionist’ and ‘vitalist’ at the same time!
15
The latest edition: OUP 2003 After several editions in Hungarian Two previous books (the Principles and Contra Crick) plus one essay Essays appreciating the biological and philosophical importance
16
The investigation of life criteria: absolute criteria 1.Inherent unity 2.Metabolism 3.Inherent stability 4.Information carrying subsystem 5.Processes regulated and controlled by a programme VERBAL AND PHENOMENOLOGICAL, BUT RIGOROUS
17
Gánti’s chemoton model ALL THREE SUBSYSTEMS ARE AUTOCATALYTIC template copying metabolism membrane growth
18
Organisation of chemical systems into a supersystem (1974) CHEMOTON: a particular supersystem which is also a biological minimal system
19
Chemical cycles are metabolic engines (1971) The cycle as a whole is a catalyst The Noble prize of Szent-Györgyi was awarded for catalysis by fumaric acid Krebs has recognized the whole cycle Enzymes are superimposed on the metabolic cycle
20
Enzymes and cycle stoichiometry Very important: the cyclic process sign with the number of turns
21
A self-reproducing vesicle (1978) Metabolism and reproduction No genetic subsystem
22
Compartments are important, because They prohibit constituents diffusing away Can increase local concentration Create a special microenvironment, e.g. by keeping many molecules out For example, imagine when a poison cannot enter the compartment The problem of the origin of life is essentially that of metabolite channelling! Last but not least: a higher-level unit of evolution
23
The fission of the chemoton Membrane surface doubled Quantity of internal materials doubled Assume spherical shape Concentration cannot be kept with a growing sphere: volume increases with the cubic of the radius Volume of sphere with a surface are doubled would be more than doubled
24
Chemoton fission II More detailed calculations based on continuum mechanics Continuous distortion of the spherical shape Final resolution: two new spheres with size identical to that of the parental sphere STRICT STOICHIOMETRIC COUPLING BETWEEN THE GROWTH OF THE SUBSYSTEMS
25
The informational subsystem The pV n molecule consists of n molecules of V Result of template polycondensation R is the by-product, necessary for the formation of the membranogenic molecule T Information carried by quantity, frequency (composition), or sequence of signs Importance of sequence increases in evolution
26
Von Kiedrowski’s replicators
27
Replication of short templates is possible By the non-enzymatic scheme of von Kiedrowski (1986) If bound to a surface, exponential growth is also possible But the latter reaction does require intervention!
28
SPREAD for replication (von Kiedrowski)
29
How are we to substitute evolved agents (such as chemists and enzymes?) A robust replication must be found NOTE: template-directed synthesis is necessary but not sufficient for replication Should be preferably non-enzymatic Should be plausible under prebiotic conditions The idea should be testable
30
At the heart of the chemoton… …there is a metabolic cycle It is autocatalytic Produces the raw materials for the functioning of all subsystems at the expense of the difference between nutrients and waste Has homeostatic capacity The Calvin cycle and the reductive citric acid cycle are such core systems (controlled by enzymes) today
31
Most biological reactions are catalyzed by protein enzymes Without catalysis the reaction is slow S P The catalyzed reaction is fast S + E ES ES EP EP E + P
32
Structures form in 3 dimensions... …and are suggestive of enzymatic capability
33
Some RNA molecules act as enzymes (ribozymes) today
34
Test-tube selection experiments yield novel ribozymes and show that Catalysis of C-C bonds was feasible Even hydrophobic molecules can be specifically recognized The RNA world is likely to have been metabolically complex
35
The assembly of RNA structures Combinatorial assembly of RNA structures Submitted to selection for function between chemotons 1979
36
The channelled assembly of ribozymes (1983) The presence of substrates gives guidance to ribozyme assembly Good enzymes and bad enzymes will affect the fitness of the chemotons
37
The major open issue Is the chemoton viable without some form of enzymatic catalysis? Does membrane confinement provide enough metabolite channelling? Is non-enzymatic replication feasible at all? EVEN IF THE CHEMOTON IS NOT FEASIBLE WITHOUT ENZYMES, IT REMAINS THE ABSTRACTION OF THE ESSENTIAL SYSTEM THAT THE ENZYMES REGULATE
38
All present-day living systems have an autocatalytic metabolic network This applies even to heterotrophs Although heterotrophs do not have an autocatalytic core cycle It is a distributed autocatalytic network A set of small molecules is NECESSARY to kick-start the life processes These compounds cannot be taken up from the medium
39
The energetic logic of catalysis Without catalysis
40
The formose ‘reaction’ formaldehyd e glycolaldehyde autocatalysi s Butlerow, 1861
41
Classification of replicators Limited heredity Unlimited heredity Holisticformose ModularVon Kiedrowski genes Limited(# of individuals) (# of types) Unlimited(# of individuals) << (# of types)
42
Is this just logical or also historical order? How much evolution did take place (presumably on surfaces) before protocells appeared?
43
Pathways of supersystem evolution boundary template metabolism M BM B B TB T M TM T M B TM B T INFRABIOLOGICAL SYSTEMS
44
An aim of the COST D27 action (President von Kiedrowski) is to facilitate collaborative emprirical and theoretical research on infrabiological systems
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.