Abstract

Life is characterized by a variety of novel materials, processes, and organizational motifs over a wide range of scales. To frame the question of its origin properly, we must ask for each of these "why is there something rather than nothing?" The most widely pursued current approaches to the origin of life involve the synthetic chemistry of particular molecule classes such as RNA, or the arrival at a replication-selection dynamic for molecules or vesicles, While these contribute to our understanding of mechanisms which may be essential to life, no approach focusing on particular materials or motifs seems to adequately address the joint problems of emergence, persistence, and interdependency for life as a whole.

In this talk I will try to frame the origin of life as the emergence of a distinct, chemically active geosphere (the biosphere as a whole) comparable in its identity to the lithosphere, hydrosphere, or atmosphere. Considering the biosphere as a starting point, rather than individual-based dynamics, emphasizes universal biosynthetic pathways and the modular logic of metabolism as keys to the first stages in emergence, stability, and interdependence, and shows how the problem of selecting the living state could have been distinct from the dominant current paradigm in biology, which concerns the generation and competitive selection of heritable variations. It also permits us to recognize that the integration of modern life, along with the distinctively biological concepts of individuality and Darwinian dynamics, emerged as dynamical counterparts to the emergent distinction of living matter.

The emergence and stabilization of a biosphere

Eric SmithSanta Fe Institute

January 2010

Colleagues and mentors: Harold Morowitz, Shelley Copley, John Baross, George Cody

Outline

• General overview of life, and the circumstantial argument for an origin through metabolism

• Framework to bring together self-organization, hierarchy, and complexity under some reliable notion of “cause”

Make everything as simple as possible, but not simpler.

Some general facts about life;Simplicities and too-often-overlooked complexities

• Broad overview: typology, chance and necessity, major transitions

• The chemical and energetic logic of metabolism

• Hierarchy, control flow, information storage, and error correction

• The surprising recurrence of metabolic motifs at all levels of organization

Two typological distinctions are most informative about the order in cellular metabolism

• Energy provided by electron donors, or by acceptors?

• Complete metabolism within single cells, or shared?

Only a chemical distinction remains for ecosystems:ecology is more fundamental than individuality

• All “complete” ecosystems are autotrophic

• Oxidation/reduction more basic than cells

Chance and necessity: life spans a continuum from thermodynamics to individuality

Ecological order is the natural bridge between geochemistry and life

O

O

OH

O

HO

O

OH

O O

HO

O

OH

NH

UniversalSteadyPredictable

VariableFluctuatingContingent

The really major transitions in evolution were chemical

-3.8Origin(?)

-3.5Photosynthesis (?)

-2.0Endosymbiosis

-0.5Cambrian explosion

The surprising simplicity, structure, and logic of the deep core of metabolism

Necessary basic metabolism

V. Srinivasan and H. J. Morowitz, Biol. Bulletin (to appear)

Biosynthesis has a unique, universal core

• Citric acid (TCA) cycle contains all biosynthetic precursors

• Found in both reducing and oxidizing organisms

• Found in all branches of life

(citrate)

malonatelipids

alanine,sugars

aspartateamino

acids,

pyrimidines

acetate

pyruvate

oxaloacetate

malate

fumarate

cis-aconitate

succinate

-ketoglutarate

oxalosuccinate

isocitrate

glutamate

amino

acids

pyrroles

In reducing organisms, core runs autocatalytically:a plausible gateway from CO2 to biomass

• 5 major chemical groups

• 6 distinct reactions

• Couples directly to H2 and CO2

• Plausible as a pre-cellular bulk reaction

acetate

pyruvate

oxaloacetate

malate

succinate

-ketoglutarate

oxalosuccinate

isocitrate

fumarate

citrate

CO2 + H2

H2O

CO2

H2

C COOHH

HH

CO2 + H2

H2O

CO2

H2

C COOHH

HC

O

H

COOHC

O

CH

HOOC

H

COOH

OH

CH

HOOC

CH

H

C COOHH

HHOOC-CH2

COOH

OH

CH

HOOC

CH

HOOC-CH2

C COOHH

HC

O

HOOC-CH2

COOHC

O

CH

HOOC

HOOC-CH2

H2O

H2

COOHC

HOOC

CH

H

cis-aconitate

COOHC

HOOC

CH

HOOC-CH2H2O

COOHCOH

HOOC

CH2HOOC-CH2

H2O

The architecture of metabolism is significantly a hierarchy of “clouds” and “gateways”

• “Gateway” molecules or pathways are unique points of connection between molecule classes

• Within classes, synthesis often resembles thermodynamic ensembles or DLA-type reaction sequences

For reducing life, energy capture proceeds via building biomass

• Transfer of e- onto C and O yields free energyfG

o / C

arb

on

H2 / CO2 (formation)

formate

methanol

ethanolpropanolbutanol

pentanol

methane

acetate

pyruvate

oxaloacetate

malatefumarate

succinate

-ketoglutarateisocitratecis-aconitate

citrate

1 1.5 2 2.5 3 3.5 4-200

-150

-100

-50

0

50

The embedding of metabolism within a hierarchy of control

Control flows and error correction

• Long-lived states “control” faster processes

• “Errors” removed by both control and selection

• References are contained in both system and environment

transcription/translation∼ 101 − 102s

catalysis∼ 10−6s

assembly,interactions

∼ 10−3 − 102s

reproduction,death

∼ 103 − 108s

regulation,placticity

∼ 101 − 106s

allostericregulation

∼ 10−3 − 100s

The ladder of catalysishierarchy recapitulates biosynthesis

• Between core metabolites and macromolecules lie a ladder of intermediate forms

• Intermediate forms seem inescapable chemically; are retained functionally

• Suggests aboriginal information flow upward through constraints on the space of possibilities

S2S1

monomer

world

multimer

world

micro-RNA

world

mini-RNA

world

S

O

OHO

PO

O

O

O

B1

O

OHOH

B2

O

OHOH

OA

P

O

O

O

P

O

O

N

O

OHOH

O

O

NH2

HH

O

OHOH

OB

R

O

OH

NH2H2NR

COO

O

H2N RSHR

= cofactor or amino acid

O

OHO

OB

O

R

NH2H

P

P

n

n

n

P

S S

S

macromolecular RNA World

= cofactor or amino acid

intercalated

"A-handle"

Even very high-level systems echo metabolic order:Code first base links the synthetic pathway to rTCA

(citrate)

acetate

pyruvate

oxaloacetate

malate

fumarate

cis-aconitate

succinate

-ketoglutarate

oxalosuccinate

isocitrate

glyoxylate

Second base is associated with physical properties

The genetic code is a manual for amino acid biosynthetic regularities (!)

first

position second position

G C A U

Gly Ala Asp/Glu Val

Gly Ala Asp/Glu Val

G

O

OH

NH2

O

OH

NH2

O

OH

NH2O

HO

O

OH

O

HO

NH2

O

OH

NH2

Arg Pro Gln Leu

Orn Pro Gln ?

C

( -ketoglutarate)

O

OHH2N

NH2

O

OH

NH

O

OH

O

H2N

NH2 ?

Ser / Arg Thr Asn Ile

Dab Hsr Asn Ile

A

(oxaloacetate)

O

OH

NH2

H2N

O

OH

NH2O

H2N

O

OH

NH2

Cys Ser Tyr/stop Leu

Cys Ser X Leu

U

(Pyruvate)

O

OH

NH2

HSX

O

OH

NH2

O

O

OH

O

HO

O

OH

O O

HO

O

OH

NH2

HO

O

OH

NH2

HO

O

O

OH

What’s to be explained?What counts as explanation?

• The unique role of chemistry as problem and solution

• The inaccessibility of covalent bonds

• Opportunities for separation of timescales

• The challenge of integrating self-organization and selection

• Directions of information flow and the problem of understanding hierarchy

• Modularity, the barrier of complexity, and the emergence of individuality

What do you make of it, Spock?

The equilibrium / dynamics inter-relation:Energetic ensembles place most chemistry out of reach

• Energy is related to probability for near-equilibrium systems

• Morals to the story:

• We might expect one bonded atom per mole by chance

• A kinetic theory must overcome these probabilities in a structured way

kBT ≈ 2.6× 10−2eV

H-bond energy ≈ 0.02− 0.3 eV

UV photon energy ≈ 3− 124 eV

P (state) ∼ e−∆G/kBT

e−50 ≈ 2× 10−22

C-CN-NO-O

bond energy ≈

3.521.5

eV

The distinction of the biosphere is access to chemistry;Individuality and even Darwinism come later

• Lithosphere

• Solid, radiation heating, metal chemistry

• Hydrosphere

• Liquid water, absorption albedo, solution chemistry

• Atmosphere

• Gas, small-light-molecules, ion/radical/electro-chemistry

• Biosphere

• Steady, high-volume energy transduction through covalent-bond chemistry

Implications of the direction of information flow for origin-of-life inferences

“Flat” systems and self-organization: our most thoroughly understood paradigm for emergence

• Major lessons from water -> ice

• Order can form without “downward causation” of any nontrivial kind

• Order is not easy to form, and cannot be taken for granted scientifically

• Predictable and inherently unpredictable components of order depend on one another

The problem of integrating self-organization and selection

• Self-organization describes order parameters, so stability is inherent

• The problem for self-organization is obtaining complex order parameters

• Selection, in principle, makes possible the elements of design (à la Dennett)

• The problem for selection is explaining stability of composite organizations

We don’t want explanatory monismWe need some approach that allows a meet in the middle

Flat organization from non-equilibrium chemistry?the energetics & network topology of carbon fixation

fGo / C

arb

on

H2 / CO2 (formation)

formate

methanol

ethanolpropanolbutanol

pentanol

methane

acetate

pyruvate

oxaloacetate

malatefumarate

succinate

-ketoglutarateisocitratecis-aconitate

citrate

1 1.5 2 2.5 3 3.5 4-200

-150

-100

-50

0

50

Cycle transport and topologyEnergetics of the TCA cycle

Carbon fixation is a microcosm of life

Autocatalytic cycles can createnon-equilibrium phase transitions

10!2

10!1

100

101

102

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

(varphi): [ACE]Gibbs

/ [ACE]crit

(J!

hat a

): J

a / (

[AC

E] G

ibb

s D

elta

AC

E)

(Acetate production current) / (loss rate at Gibbs value)

[ACE]boundary

/ [ACE]crit

!> 0

From self-organization to complexity: key concept?Modularity, modularity, modularity!

• Modularity 1: Is it seen empirically? In what forms?

• Modularity 2: For adaptability? or evidence of earlier separateness?

• Modularity 3: (Simon, Proc.Am.Phil.Soc. 106, 1962) Separate module stability: the only path to complexity?

Modularity in core carbon anabolism

Phosphorylated

Primary redox couples

Hydrocarbon redox states

Modularity in carbon fixation reflects a modularity in chemical energy systems

fGo /

Ca

rbo

n

H2 / CO2 (formation)

formate

methanol

ethanolpropanolbutanol

pentanol

methane

acetate

pyruvate

oxaloacetate

malatefumarate

succinate

-ketoglutarateisocitratecis-aconitate

citrate

1 1.5 2 2.5 3 3.5 4-200

-150

-100

-50

0

50

Modularity and micro-environments:canalization and the emergence of integration

• Perhaps best seen in energy metabolism

• Modern cells couple synthetic modules by coupling and buffering energy carriers

• Ox-phos supplements / supersedes substrate-level phosphorylation

• Ox-phos is membrane-mediated, plausibly the last step in emergence (several arguments for this)

Summary of our trip through the fog:Do we think any better from these observations?

• The question “Why is there something instead of nothing?” refocuses discussion away from entrenched paradigms (synthetic chemistry; genetics) and toward information storage, error correction, and distributed control

• “Metabolism first” (with continuity to today) is vague and circumstantial, but sane in light of the logic of biosynthesis, energetics, and physiology

• The right conversation between metabolists and geneticists is not an opposition, and it is not conceptually simple along any familiar lines

• Better physics input = order parameters and stability; better biology input = canalization, regulation, emergence of individuality (+ Darwin)

But also to not oversimplify for its own sake...

Horatio:O day and night, but this is wondrous strange!

Hamlet:And therefore as a stranger give it welcome.There are more things in heaven and earth, Horatio,Than are dreamt of in your philosophy.

Support

• Research supported by NSF grant # EF-0526747: FIBR: From geochemistry to the genetic code

• DES supported through SFI by Insight Venture Partners

References

• Vijayasarathy Srinivasan and Harold J. Morowitz, The canonical network of autotrophic intermediary metabolism; Analysis of the intermediary metabolism of a reductive chemoautotroph, Biol. Bull. (to appear 2009)

• Herbert A. Simon, The architecture of complexity, Proc. Am. Phil. Soc. 106:467 -- 482 (1962)

• Shelley D. Copley, Eric Smith, and Harold J. Morowitz, A mechanism for the association of amino acids with their codons and the origin of the genetic code, Proc. Nat. Acad. Sci. USA 102:4442 -- 4447 (2005)

• Shelley D. Copley, Eric Smith, and Harold J. Morowitz, The origin of the RNA world: co-evolution of genes and metabolism, Bioorganic chemistry 35:430 -- 443 (2007)

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