L2 : Origins and Evolution of Life

Question 1

2 or 3 domains of life?

Answer 1

Recent work suggests only two primary domains of life
Eukaryotes are derived through endosymbiosis

Question 2

Why compare bacteria and archaea?

Answer 2

To understand and reconstruct properties of LUCA

Question 3

What are likely characteristics of the first cells?

Answer 3

Chemiosmotic - use proton gradients for energy
Thermophilic
Autotrophic - fixed carbon from CO2

Likely thrived in extreme environments

Question 4

What are some paradoxical traits of bacteria and archaea?

Answer 4

Membrane bioenergetics are universally conserved but cell membranes are not

Transcription and translation processes similar but appears DNA replication arose independently

Respiratory chains also differ

Question 5

Where was life predicted to begin?

Answer 5

Alkaline hydrothermal vents (Lost City vent field) with geological proton gradients (could resolve paradox)
Inorganic vent pores appear analogous to autotrophic cells

Question 6

What is the hypothesis on the origin of life?

Answer 6

Inorganic pores may have evolved into organic cells

Electrical charge (proton motive force) drives reaction between H2 and CO2 to form protocells in alkaline pores, eventually leading to metabolism, growth, and emergence of genes

Question 7

What are key features of electrochemical flow reactors?

Answer 7

High conc of H2 and CO2
H+ gradients across catalytic Fe(Ni)S walls

Alkaline hydrothermal vents act as natural electrochemical reactors

Predicted as location for origin of life before existence was known (Lost City)

Question 8

Is abiotic organic synthesis from H2 + CO2 possible? Step 1?

Answer 8

Synthesising cell biomass from H2 + CO2 is exergonic under alkaline hydrothermal conditions
Thermodynamically possible but kinetic barriers prevent it

Question 9

How did methanogens and acetogens influence early life theories?

Answer 9

Generally considered some of the most ancient groups

Acetyl CoA pathway is only CO2 fixation pathway found in both archaea and bacteria

Give clues on nature of LUCA

Question 10

How could geological proton gradients contribute to origin of life?

Answer 10

Alkaline hydrothermal vents create H+ gradients across Fe(Ni)S catalytic walls
Proton gradients gradients may have lowered energy barrier driven CO2 fixation using H2 as reductant

Analogous to modern methanogens

Question 11

How do proton gradients influence redox potential of H2 and CO2

Answer 11

In alkaline conditions
H2 becomes stronger reductant
Potential for spontaneous CO2 fixation driven by proton gradients

Question 12

What is Ech?

Answer 12

Energy converting hydrogenase
Membrane protein that contains 4Fe4S clusters

Question 13

What minerals resemble FeS clusters and may have catalysed early CO2 fixation

Answer 13

Greigite and FeS minerals, which resemble the active sites of modern enzymes, including ferredoxin and hydrogenases

Question 14

How does Ech work?

Answer 14

Uses FeS clusters and proton motive to drive work and reduce ferredoxin, Fd can then fix CO2 and power carbon metabolism

Redox potential depends on lower pH

Question 15

What are the hypothetical conditions in vents?

Answer 15

pH = 5-12
Temp = 50-100
Salinity = NaCl (600mM)
Divalent cations = Mg2+, Ca2+

Question 16

Is hydrothermal synthesis of long-chain lipids possible? Step 2?

Answer 16

Thought to have occured through FTT (Fischer-Tropsch type) synthesis reactions on mineral surfaces
Possible under these conditions
Starting from H2 and CO2, chain lengths are similar to modern membrane lipids

Question 17

Are vent conditions too extreme for fatty acid membranes? Step 2?

Answer 17

No
Experiments show FA:FOH vesicles (protocells) are stable under extreme conditions
- pH 12, 70 deg, high salinity

Question 18

Are FeS clusters able to form under these conditions?

Answer 18

Low potential FeS clusters shown to form spontaneously from cysteine, Fe3+, S2- under alkaline conditions
FeS clusters can fix CO2 on electrode

Question 19

Can CO2 fixation drive spontaneous metabolism?

Answer 19

Sequential reactions of H2 + CO2 in biology give rise to acetyl CoA and Krebs cycle intermediates
AAs, FAs and sugars all derive from Krebs cycle intermediates

Question 20

What makes autotrophic metabolism likely prebiotic?

Answer 20

Near equilibrium
Spontaneous under right conditions
Yields core biomolecules

Question 21

What universal intermediates derive from CO2 and H2 reactions?

Answer 21

Acetyl CoA
Krebs cycle intermediates
AAs, FAs, sugars

Question 22

Why is metabolism considered older than genes?

Answer 22

Reaction network topology of autotrophic metabolism is universally conserved across life
Functions spontaneously (in absence of genes)

Question 23

How does direction of flux depend on environment?

Answer 23

Metabolism is quite close to equilibrium
- metabolic intermediates interchange easily

Concentration differences will tend to drive flux in one direction

Question 24

Directionality in early metabolism?

Answer 24

Environmental disequilibrium between H2 and CO2 creates flux towards biosynthesis

Question 25

What may have led to the emergence of heterotrophy?

Answer 25

Reversal of autotrophy Dissipation of environmental disequilibrium causes accumulation of products, reversing directionality of metabolic flux

Question 26

Amino acid synthesis and interconversion

Answer 26

Through transamination of oxoloacetate in presence of pyridoxamine and metal ions Yield depends on specific metal ions

Question 27

What experiment investigated prebiotic formation of AAs? Results?

Answer 27

GC-MS and HPLC detection show Asp, Ala, Gly, Ser, Cys all formed in presence of pyridoxamine + metal ions

Question 28

Is uracil synthesis possible?

Answer 28

One pot synthesis of uracil from ammonia, carbonate, and aspartate - Optimised at 90 deg, pH 9, 1M NaOH

Question 29

Is ATP synthesis possible?

Answer 29

Only need water, ferric iron and 2C phosphate donor (acetyl phosphate) - Does not work for other nucleotide triphosphates

Question 30

What does experiments on formation of AA, uracil, ATP collectively show?

Answer 30

Shows all these intermediates are able to spontaneously interchange

Question 31

What does computer simulation show about rudimentary membrane heredity in protocells?

Answer 31

AAs chelate FeS crystals, hindering growth and giving more smaller crystals (larger SA) Chelation by amino acids partitions FeS crystals to membrane, giving 'proto-Ech'

Question 32

How could natural proton gradients affect protocell evolution?

Answer 32

Drive formation of new organics via proto-Ech Enables positive feedback loops that support growth

Question 33

What was the original role of nucleotide cofactors?

Answer 33

Involvement in metabolism - CO2 fixation - possible catalysing other pathways - facilitating redox reactions Autocatalysis - increase ATP synthesis - positive feedback Theoretically may have led to accumulation of nucleotides, though not observed in prebiotic experiments

Question 34

Describe potential emergence of genetic code from polymerising nucleotides?

Answer 34

Biophysical interactions mean random RNA will template non-random peptides so information has meaning in protocells

Question 35

Do biophysical interactions enable evolution?

Answer 35

Simple mathematical model introducing random RNA into autotrophically growing protocells shows: Random peptides produced may feedback somehow

Question 36

What does evolution depend on?

Answer 36

Low free polymerisation rate - Production of too many random sequences is dilutes potentially useful ones Higher error rates undermine selection

Question 36

What kind of peptides support evolution and how?

Answer 36

Hydrophobic peptides - Embed in membrane ad drive CO2 fixation Hydrophilic peptides - Facilitate RNA copying, creating selection of RNA sequences

Question 37

What are the 3 steps in the origins of life?

Answer 37

1. Proton gradient drives CO2 fixation, reacting with H2 to form carboxylic acids, AAs, lipids under favourable conditions 2. CO2 fixation drives spontaneous metabolism, forming network of intermediates of acetyl CoA and Krebs cycle 3. Metabolism gives rise to genetic information