life’s requirements (in two takes) tori hoehler, nasa ames [email protected]
TRANSCRIPT
Take 1:Life as We Know It
Complexity, Organization, Order(Among other things) life is an emergent property of big, complicated
molecules that interact in an organized way
Raw Materials
(water)
Energy
(T, pH, S, etc.)
Requirements for Complexity
SolventClement
Conditions
(SPONCH, e-) (light, chemical)
“It feeds upon negative entropy”
“How would we express in terms of statistical
theory that marvelous faculty of a living
organism, by which it delays the decay into
thermodynamic equilibrium (death)?”
Why Energy? It’s The (2nd) Law . . .
(The awesome destructive power of the four year-old boy)
Exhibit A
Energy expenditure to maintain a complex, ordered state
(Disorder + my hard work → Organized LR)
(Organized LR + kid → Disorder)
“Process” increases entropy in the system
11am
9pm
7am
Earth life uses only a subset of available light and chemical energy, which themselves are a subset of available forms
But Energy is Everywhere . . .
(Our) biology uses only a small part of the EM spectrum for energy
There’s a pretty fundamental reason for this!
A General Scheme of Energy Transduction (Earth Life)
Light: Photon energy sufficient to cause electronic transitions of desirable type**. Significantly exceeds energy for ion gradient formation.
Electron flowTrans-membrane
cation gradientHigh-energy
covalent bond
Chemical: Electron transfer (redox) reactions with sufficient Gibbs energy to establish cation gradient (approx 10 kJ/mol; ultimately set by energy of covalent bond in final step)
Approx. 1015 – 1022 photons∙m-2∙s-1 (PAR)
Approx. 400-1025 nm
Flux (Power)
Wavelength (Voltage)
Too “Hot” Too “Cold”
A Fundamental Constraint on the use of Light Energy
Different wavelengths (energies) of light interact differently with matter
Life Requires…
This statement encompasses three elements:
“An environment capable of maintaining covalent bonds, especially between C, H, and other atoms”
Clement environmental conditions
Covalent bonds (= molecules)
Raw materials
Life Requires
This requires both covalent and non-covalent interactions.
Raw materials, environmental conditions, and solvent (which we’ll come back to) all need to be considered
in this context.
A diverse library of complex molecules that interact
Covalent vs. Non-Covalent Interactions
Non-Covalent
Covalent
Non-Covalent: No shared electrons. Interactions (molecular recognition, “Dating” tertiary structure, self-organization).
Covalent: Shared electrons. Primary molecular structure and properties. “Marriage”
How to make complex, interesting molecules that interact
Heteroatoms (“sticky bits”)
Electrons
Scaffolding
To “glue” molecules together
Capable of creating a large, diverse library of molecular skeletons
Capable of bonding to multiple heteroatoms
Creates structures that are stable, but not too stable
When bonded to scaffold or each other, create potential for an array of non-covalent interactions (incl. directional or hydrogen bonds?)
Raw Materials:
A lesson from Earth . . .
Everything a Body Needs?
Scaffolding element (C): Capable of forming 4 bonds
Dominantly in intermediate oxidation state*
Electrons Needed!… to make (a diverse library of) biomolecules from CO2
Molecular Diversity vs. Oxidation Statein Terrestrial Biochemistry*
Earth:
Molecular diversity requires intermediate oxidation state, but elements (esp. C) are available in oxidized form.
Life needs electrons and water H—O—H is all around.
Bains & Seager, 2012
Mo
st ava
ilab
le ca
rbo
n
at E
arth
’s surfa
ce
Sugars
Everything a Body Needs?
+
Relatively labile covalent bondsHeteroatoms (SPONH):
Scaffolding element (C): Capable of forming 4 bonds
Central to enzyme & cofactor function
Dominantly in intermediate oxidation state*
Coordination chemistry
Tertiary structure
Molecular recognition
“Minerals”:
Electrostatic interactions
Heteroatoms and Non-Covalent Interactions
Bottom LineRequirements for (our) Life
Source of Carbon
Source of Electrons
Nutrients
Source of Energy Water
Microbiologists classify organisms based on how they fulfill these needs
Clement Conditions?Must be compatible with both covalent bonding and non-covalent interactions
What conditions threaten the integrity and interaction of big,
complex biomolecules?
Radiation
Strong Acid/Base
Pressure
Heat
Temperature: -25 to +122˚C (growth)
pH: approx. 0 to 12 extracellular
Water Activity:approx. 0.6 (incl. NaCl saturation)
Pressure: approx. 200 MPa*
OK, fine, but what about the Horta?
Take 2:
There is a famous book published about 1912 by Lawrence J. Henderson . . . in which Henderson concludes that life
necessarily must be based on carbon and water, and have its higher forms
metabolizing free oxygen. I personally find this conclusion suspect, if only
because Lawrence Henderson was made of carbon and water and metabolized free oxygen. Henderson had a vested interest.
Carl Sagan
The “TerraCentric” Problem
(“The Weird Life Report”)
“The Limits of Organic Life in Planetary Systems”
Theory, data, and experiments suggest that life requires
(in decreasing order of certainty):
A molecular system that can support Darwinian evolution
Thermodynamic disequilibrium (Gibbs energy)*
An environment capable of maintaining covalent bonds, especially between C, H, and other atoms
A liquid environment**
OK, fine, but what about the Horta (Crystalline Entity)?
SolventEnvironmental
ConditionsRaw Materials(esp. scaffold)
These are Interdependent!
Report of the NRC Committee on the Limits of Organic Life in Planetary Systems(aka “The Weird Life Report”)
Thermodynamic Disequilibrium
(Gibbs Energy)
“…the requirement for thermodynamic disequilibrium is so deeply rooted in
our understanding of physics and chemistry that it is not disputable as a
requirement for life.
Other criteria are not absolute.”
Life Requires…
Why Does Life Need Energy?
Energy is required to reliably populate states (produce outcomes) of otherwise low probability
Creation and replication of information (e.g., generation of specific sequences)
Creation of locally ordered states
Production of thermodynamically unfavorable species
(Take 2)
(example: production of thermodynamically unfavorable species)
ΔGA→B = ΔG˚ + RT∙ln({B}/{A})
Addition of energy can drive an otherwise improbable outcome (and we know how much energy is needed)
The probability of the outcome, and the energy needed to overcome low probabilities, are affected by physicochemical environment
ΔGA→B is a quantitative measure of probability (e.g., large positive value = very low probability)
A → B←
(aqueous at 298K)
Life overcomes the low (!) probability of net forward progress in this reaction by application of 2 visible photons’ worth of energy
Other “low probability” properties/processes of biological systems can be addressed in the same way by life, and contemplated in the same way by us. For example . . .
2H2O → O2 + 2H2←ΔG˚ = +526 kJ∙(mol O2)-1; Keq = 6 x 10-93
(and the importance of doing it with high fidelity)
Information Processing as a Core Attribute of Life
(Weird Life Report: Life requires…a system capable of Darwinian evolution)
Shall I Compare Thee…?
Model Assumptions:
101-key standard keyboard
12-hour shifts (according labor laws)
50 5-letter words per minute
Correct punctuation, spaces, and returns, but not capitalization
1000 monkeys typing on 1000 typewriters for 1000 years . . .
Could be expected to correctly reproduce a specified sequence of 10 amino acids (not more), given a keyboard of 20 characters
Have a probability of 10-1255 of correctly reproducing Sonnet #18
Have about a 10% chance of correctly reproducing “Shall I”
Probability of randomly constructing a specified 200-bit sequence where each bit has 20 possible values (i.e., a protein) is approx. 10-260, requiring energy > 1484
kJ/mol
Life Requires…
“A Liquid Environment”
Pohorille on the Importance of Solvent(see: http://astrobiology.nasa.gov/nai/seminars/detail/161)
Much of the business of life is conducted through non-covalent interactions (e.g., molecular recognition)
Non-covalent interactions depend heavily on the solvent in which they occur
Electrostatic and solvophobic interactions have comparable strength in water, allowing a
greater range of organizational possibilities
Life requires a solvent capable of mediating
life-like chemistry
Life requires a solvent capable of mediating
life-like chemistry
Are there alternatives to liquid water?Are there alternatives to liquid water?
Non-Covalent Interactions
Van der Waal’s
Solvophobic
Strength strongly solvent dependent(water > non-polar solvents, for non-polar solutes)
Variable in strength
Directional (mostly)
Based on complementarity
Electrostatic
Non-specific (everything sees everything)
Weak
∆ A
(kc
al/m
ol)
∆ A
(kc
al/m
ol)
Separation (Å)
CH4 - CH4 in water(Hydrophobic)
Na+ Cl- in DMSO
(Courtesy A. Pohorille)
Strength of Non-Covalent Interactions in Water
(Electrostatic)
Hypothesis
Electrostatic and solvophobic interactions are necessary to confer life-like specificity, but are too stable/weak
(respectively) in non-polar solvents to function effectively as arbiters of molecular interaction.
(So, water – or something very like water – is necessary for life)
Focus/Example:
Information processing (molecular recognition) with high fidelity
Selectivity in Molecular Recognition
Importance of Electrostatic Interactions
Valine
Phenylalanine
Isoleucine
Tyrosine
Discrimination during activation by AAtRNA Synthetase
>104:1
102:1
Electrostatic effect gives 100-fold enhancement in fidelity of
molecular recognitiion
non-polar
polar
Fidelity in Information Processing
Information: G-A-T-T-A-C-A
1 “byte”1 “bit”
“Reliable” (>90% successful) replication of 600 Kbit of information requires error rate < 10-7
(> 107-fold discrimination among possible states)
Smallest free-living organism = 600 Kbit (Humans = 3 Gbit)
Observed error rates during DNA replication are 10-8 to 10-10
Selectivity in Chemical Processes
Thermodynamicthe system must be able to sample (interconvert between) possible states a large number of times
Kinetic
S2S1ΔG = 0 = ΔG˚ + 2.3 RT log (S2/S1)
at equilibriumat 298K
S2/S1 ΔG˚ (kJ/mol)
-23
-57
104
1010
-40107
One H-bond is worth approx. 20kJ/mol. Hmmm….
Stability of Electrostatic Interactions
correct complex stabilized by60 kJ/mol relative to alternatives
(1 bit at error rate 10-10)
HHO
:
:
HH
O::
H
H O:
:
Less stable than complexed form by 60 kJ/mol) in non-polar
solvent
UncomplexedComplexed
Water-solvated form approx. as stable as
complexed form
Energy in Information
Total Energy (kJ/mol)Information Content
Complex dissociation
in nps*
Stabilization vs. incorrectalternatives
Stabilizationvs. solvation
in water*
DNA**
*If stabilization derived entirely from electrostatic interactions
0
0
75000
150
“protein’s worth”
1 bit
1 byte
3x107600 Kbit
0 75000
150
3x107
050 50
**DNA: Average 2.5 H-bond = 50 kJ/mol per bit = hypothetical error rate 10-9
Strength/Stability of C-C bond corresponds to about 10 bits worth of information
OK, fine, but what about the Horta (Crystalline Entity)?
SolventEnvironmental
ConditionsRaw Materials(esp. scaffold)
These are Interdependent!
Ruling Out Alternatives to Liquid Water . . .
Allows application of liquid water phase constraints
Rules out covalent chemistry that is unstable (or too stable) with respect to:
(a) the chemical reactivity of water, or (b) the temperature range in which water is liquid, or (c) both
(silicon: gone; carbon: decreased temp range for stability of C-C and C-X relative to non-polar solvents)
Covalent Chemistry:Are there Alternatives to SPONCH?
Makes this range of bonds with strengths/reactivities that are stable, but not too stable, with respect to the ambient physicochemical environment
Example: Is Si a Suitable Scaffolding Element?Can create a large combinatorial chemical space (a large and diverse set of possible molecules on which to build a metabolism), esp. by bonding to itself
Can support a diverse array of non-covalent interactions by bonding to a range of heteroatoms
Si(see Bains, 2004; Benner et al., 2004)
Silicon is observed to meet the first two requirements at a proof-of-concept level (although less effectively than carbon)
Meets the third criteria only in non-polar cryosolvents
Clement Conditions?(highly dependent on solvent, biochemistry)
pH
Always a problem, perhaps esp. in low T, low energy systems
Low
High
Radiation
Heat is always a problem for complexity (2nd Law)Fewer bond types stable as T increases (esp. for protic solvents)
Solubility a problem
Temperature
Extant life on Earth tolerates much of environmentally realistic range
Ruling Out Alternatives to Liquid Water . . .
May serve to significantly constrain the type of biosignatures that can be produced by photosynthesis, and the circumstances under which they can be expected (does specifying water specify O2?)
Allows application of liquid water phase constraints
Rules out covalent chemistry that is unstable (or too stable) with respect to:
(a) the chemical reactivity of water, or (b) the temperature range in which water is liquid, or (c) both
(silicon: gone; carbon: decreased temp range for stability of C-C and C-X relative to non-polar solvents)
The Bottom Line:It is important to think broadly and creatively about the possibilities for life. But basic principles of physics and chemistry offer more constraint than might be imagined…
Some Final Caveats
Conditions achievable w/ different biochemistry?
Conditions conducive to origin of life
Conditions tolerated by extant life
Early (= core) biochemical choices may lock organisms in to a narrower range of conditions than could ultimately be explored by a similar biochemistry (example: temperature)
Compartmentalization & energy expenditure allow extant life to tolerate conditions likely unsuitable for origin of life chemistry (example: pH)