D. J. Scott
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“Mitochondrigeny”
The Origin & The Evolution of The Mitochondrion, and Possible Implications for Astrobiology
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The Origin of Life
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The Origin of Eukaryotic Life


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D. Jon Scott’s WebsiteSciencePhysicsChemistry ► Organic Chemistry

LUCA

The Last Universal Common Ancestor
Copyright © 2018 by Dustin Jon Scott
[Last Update: June 6th, 2018]

Abstract



I.b-1.) The Last Universal Common Ancestor (LUCA)

While the progenitor of the eukarya is now traditionally nested within the archaea, Carl Woese (1998) suggests that the Last Universal Common Ancestor (LUCA) of the three domains may antedate individuation into discrete lifeforms separated by cell membranes, and that the LUCA may have actually been a community of proto-cells with extremely primitive, porous membranes — called "progenotes" (Woese, 1998) — through which, due to pervasive lateral gene transfer (LGT) (Woese, 2002), genetic material was exchanged and propogated itself more-or-less freely. The picture this evokes is one in which, prior to the “Darwininian threshold" (Woese, 2002), the primary, smallest, most irreducible unit of life was less like a modern cell than like a modern chromosome.

Other authors (e.g. Martin & Russell, 2003; Koonin, 2014) have taken up modifications of Woese's theory which agree that the common ancestor of the Archaea and the Bacteria was a pre-organismal, pre-Darwinian community, but which take this further in hypothesizing that the last common ancestral state (LUCAS) was pre-cellular, and which reassert the importance of Endosymbiotic Theory in understanding the origin of the eukarya. If true, this would mean that the bacteria, whence the mitochondria evolved, and the archaea, a lineage of which went on to become the eukarya, represent two separate evolutions of "true" (discrete, cellular) life. The consequences of this are that (1) the divergence of the two prokaryotic domains from a common ancestor is inextricably interwoven with the origins of life, and (2) that eukaryogenesis represents both a novel convergence of two independently evolved forms of life and a genetic reconvergence of hereditary material that had been separated since before the origin of "true" life.

This view is not universally accepted, with some authors going so far as to adopt literary bravados which (wrongfully) assert that this idea has been abandoned due to common membrane-encoding genes shared by all three domains (e.g., Forterre, 2014), alternate explanations for these shared genes, such as lateral gene transfer (LGT), or even (plausibly, considering the small size and streamlined organization of prokaryotic genomes) convergenet evolution, have not been ruled out.



I.b-1A.) The Terrestrial Origin of Life

Currently there are two primary approaches to the scientific investigation into the origins of life: the replicator-first approach and metabolism-first approach (Anet, 2004). These approaches differ conceptually in hypothesizing either an autocatalytic string of covalently bonded informational molecules at least functionally akin to DNA, or a sequence of chemical reactions a among set of noncovalently bonded molecules that was autocatalytic as whole and thus functionally akin to metabolism (von Meijenfeldt, 2013), as the essential origin of life.

Here it should be noted that the designations "replicator-first" or "metabolism-first" may apply either literally or figuratively. An approach which places primary emphasis on replication over metabolism, for example, may be regarded as a "replicator-first" approach even if it is not literally suggesting that replicators antedate metabolic systems, and vice versa. These are designations of emphasis, not necessarily descriptors of sequence.

(Delaye & Lazcano, 2005)



I.b-1Aα.) Replicator-First Approach

The most crucial entity in and most basal unit of evolution is the replicator (Zachar, 2010).

Since the 1982 discovery of ribozymes (Kruger et al.) proved that RNA had catalytic properties, and could therefore “act both as information carrier and as catalyst” (Alberts et al., 2002), resolved the DNA-protein “chicken & egg” paradox by demonstrating that RNA could act as both “chicken” and “egg” (Bernhardt, 2012; Sankaran, 2013), the replicator-first approach has quite naturally come to be dominated by the “RNA World” hypothesis (von Meijenfeldt, 2013) and this has only been reinforced by the now much-expanded catalytic repertoire of RNA and the import thereof with regard to key cellular reactions (Doudna & Cech, 2002) “which can be viewed as molecular fossils of an earlier world,” meaning we never fully transitioned out of the RNA World (Alberts et al., 2002). Evidence indicating that the common ancestor of the Archaea and the Bacteria possessed an RNA-based genome (Leipe & al., 1999) and only after divergence each separately acquired DNA from DNA viruses, in which DNA first arose (Leipe & al., 1999; Forterre, 2002), has further reinforced this hypothesis.

(Achbergerová & Nahálka, 2011)

(Fegley & Lewis, 1980)

"messy RNA" (Szostak, 2017)



I.a-1Aβ.) Metabolism-First Approaches

Emphasizing ecosystems over discrete organisms and metabolism over reproduction, Eric Smith et al. have characterized the emergence of Earth's biosphere as a sort of geochemical "discharge" resulting from a build-up of energy between the hydrosphere and the lithosphere (Smith, 2007; 2015).

(Smith &al., 2004)

(Copley &al., 2007)

(Morowitz &al., 2008)

Water is necessary to fold proteins (McLain, 2017)

first cells (Szostak, 2017)

(Hazen, 2005)

(Hazen, 2006)

(Hazen & Sverjensky, 2010)

(Hazen & Deamer, 2006)

(Hazen, 2006)

(Deamer &al., 2002)

(Deamer & Monnard, 2006)



I.b-1Aγ.) Problems with a Terrestrial Origin

While the "plausibility" criterion for a given chemical pathway suggested as being involved in prebiotic synthesis generally requires that the chemical environment has to be one which could have plausibly been present on the early Earth, such a criterion ignores that the early Earth isn't the only place that life could have formed. Such is an a priori assumption completely unsupported, and one might go so far as to say contradicted, by all experimental and observational data thus far gathered. The Earth is but one planet among hundreds known and among billions thought to exist in our galaxy alone. Furthermore, there is no particular reason to hypothesize that the generation of life is something which must occur on a planet at all! Especially when one considers how early in the geological record life first began to appear on Earth, other environments such as other Solar planets, exoplanets, planetesimals, asteroids, comets, moons, protoplanetary disks, protostellar nebulae and the stelliferous nebulae (star-forming regions of giant molecular clouds) to which they belong, as well as any interactions between such systems, must all be considered as potential environments for the various stages of prebiotic synthesis, and "plausibility" determined only when a particular chemical pathway has been demonstrated to be likely (or not) in one of such environments. An early-Earth-based "plausibility" criterion is, frankly, an unnatural constraint which ignores the fact that in our universe, no planet is an island.

Many stages of prebiotic synthesis wouldn't have worked out in hydrothermal vent scanrios or on a hot early Earth.

1.

The half-lives of the nucleobases guanine, adenine, cytosine, and uracil are far too short (t½ for adenine and guanine ≈ 1 year; uracil = 12 years; cytosine = 19 days) at the 80-110°C temperatures hypothesized in hydrothermal vent scenarios for the origin of life (based on the preferred temperature ranges of hyperthermophiles, assumed by hydrothermal vent scenarios to be among the oldest extant lineages of living things), and indeed are too unstable at temperatures much above 0°C, to allow for the formation of the first replicators in a reasonably long timespan, indicating a low-temperature origin of life (Levy & Miller, 1998).

2.

RNA hydrolyzes rapidly (Szostak, 2012; part 3), and is especially prone to doing so in hot environments, much to the chagrin of those who favor hydrothermal vent models for the origin of life.

3.

While hydrothermal vent hypotheses imply a hyperthermophilic progenote with an optimal growth temperature (OGT) ≥80°C, which is consistent with thermophilia (OGT=65±15°C) in the last bacterial ancestor as well as the last archaeal ancestor as part of a more-or-less linear progression to the overwhelmingly mesophilic (OGT≤50°C) modern prokaryotic domains, dual phylogenic rRNA and protein analyses show that while both the bacterial ancestor and the archaeal ancestor were thermophilic (OGT=65°C±15°C), the LUCA was mesophilic with an OGT≤50°C (Boussau &al., 2008).

4.

The very first protocells were likely obligate cryophiles with an OGT≈1°C (Szostak, 2012; part 1)

The hydrothermal vent model, though seemingly ruled out, would give us a mathematically elegant and thermodynamically sensible sequence of OGT≥80°C, OGT=65±15°C, OGT≤50°C and a cellular LUCA model gives us a progressive OGT≈0°C, OGT≤50°C, OGT=65±15°C thermotolerance sequence before a general decline to OGT≤50°C with a few modern lineages OGT=65±15°C or even OGT≥80°C, while a precellular LUCA model merely gives us an OGT≤50°C; OGT≥50°C threshold separating the cryophilic-to-mesophilic nucleobases, RNA, LUCA, and protocells, and the thermophilic-to-hyperthermophilic first true lifeforms, followed eventually by diversification into various levels of thermotolerance.

(Szostak, 2012; part 2)

(Sleep, 2010)

Cool Early Earth model.

Here, however, we run into another problem. Water is highly corrosive, and would've been deadly to the first RNA-based replicators (Barras, 2014)

(Ricardo &al., 2004)

(Benner &al., 2012)



I.b-1B.) The Possibility of Panspermia

The hardiness of bacteria features in many lithopanspermia models, the most conservative of which are interplanetary lithopanspermia models, most relavent to we Earthlings in the hypothetical case of Mars-Earth interplanetary lithopanspermia, in which life found its way to Earth from our neighbor, Mars.

We know that bacteria could have been ejected into space by planetary impacts (Stoffler et al. 2006), survive the subsequent rapid acceleration (Mastrapaa et al. 2001), survive exposure to vacuum and high radiation (Saffary &al., 2002; Bucker & Horneck, 1970; Horneck, 1971; Nicholson, &al. 2005), thrive and grow in asteroidal and meteoritic interiors (Mautner 2002), survive re-entry into a planetary atmosphere (blah) and subsequent impact (blah),

Deinococcus radiodurans, first isolated in Corvallis, Oregon, in 1956 (Anderson, &al.)



I.a-1Bα.) Interplanetary Lithopanspermia

Radioresistance in bacteria. Mars fertile for life before Earth.

(Hoch & Losick, 1997)

(Fajardo-Cavazos &al., 1997)

(Matti &al., 2009)

(Clark, 2001)

(Loupkin, 2006)

“So, back to the period of heavy bombardment and with computer simulations you can, you can model what happens when an impact hits a planetary surface. And it's not much different from if you sprinkle Cheerios on a bed [...] and then you smack the surface of the bed, there's a— a sort of a recoil in effect and Cheerios pop upwards. It turns out Mars may have been wet — we've known at some point it had water — and fertile for life before Earth, and at this period of heavy bombardment if it had started life — surely it would've been simple life, as we've no reason to think otherwise — we've learned bacteria can be quite hardy, as I'm sure you know, so we imagine a bacterial stowaway in the nooks and crannies in one of these rocks that are cast back into space. In fact if you do the calculation, there's hundreds of tons of Mars rocks that should that should have fallen to Earth by now, over the history of the Solar system. Maybe one of those rocks carried life from Mars to Earth, seeding life on Earth. My great disappointment would be going to Mars and finding Mars life based on DNA. That it would not've been a separate experiment in life.” — Neil Degrasse Tyson to Richard Dawkins (Dawkins & Tyson, 2016, 6:05-7:24 minutes in)


I.a-1Bβ.) Interstellar Lithopanspermia

Microbe-containing impact ejecta from Earth may be subsequently pulverized by collisions into micron-sized particles that, though large enough to contain colonies of microbial life and shield them from UV radiation, would be small enough to be carried out to the Kuiper Belt via Solar winds eventually to be deposited in the protoplanetary discs of future planetary systems as the Solar system moves through interstellar dust clouds in its course through the Milky Way (Wallis, 2003; Napier, 2003), seeding the Milky Way in just a few billion years, which, considering any Earth-like planet could hypothetically have done the same, makes it highly unlikely that Earth Herself was not a benefactor of such a process (Napier, 2003).



V. Conclusions



V.a. Summary



V.a-1.) Timeline of Events

— formation of the Milky Way

— formation of the Giant Molecular Cloud (GMC), 106-108 M (Montmerle, 2006), containing complex organic molecules (Ehrenfreund & Charnley, 2000)

— formation of a star-forming region similar to the Orion Nebula
"in a large star-forming region that produced massive stars, possibly similar to the Orion Nebula.[16][17] Studies of the structure of the Kuiper belt and of anomalous materials within it suggest that the Sun formed within a cluster of between 1,000 and 10,000 stars with a diameter of between 6.5 and 19.5 light years and a collective mass of 3,000 M. This cluster began to break apart between 135 million and 535 million years after formation.[18][19]"

— fragmentation of the GMC, first into fragments 1 parsec in diameter and then into "cloudlets" 0.01-0.1 parsecs or 2k-20k AU in diameter and around 1 M (Montmerle, 2006).

— formation of the Pre-Solar Nebula, a fragment of the GMC about 1 M (Montmerle, 2006).

4.6 GYA — beginning of the Stellar era (first million years of Solar evolution), the Disk era (first 10 million years of Solar evolution), and the Telluric era (first 100 million years of Solar evolution): formation of the Sun in a stellar cluster via accretion of a circumstellar disk fed by a progressively diminishing circumstellar envelope (Montmerle, 2006), possibly incited by a nearby supernova (Montmerle, 2006; Williams, 2009).

4.599 GYA — Stellar era ends, 99 million years prior to the end of the Telluric era and 90 million years prior to the end of the Disk era (Montmerle, 2006).

4.59 GYA — Disk era ends, 90 million years prior to the end of the Telluric era (Montmerle, 2006).

4.5682 GYA — oldest solid material in the Solar system.

4.55 GYA — formation of the Earth

4.53 GYA — formation of the Moon

4.5 GYA — Telluric era ends. Noachian period begins on Mars.

"Several simulations of our young Sun interacting with close-passing stars over the first 100 million years of its life produce anomalous orbits observed in the outer Solar System, such as detached objects.[20]"

(Brasser &al. 2013)

(Brasser &al. 2017)

(Lykawka & Ito, 2013)

4.4 GYA — "Cool Early Earth" begins

(Valley &al., 2002)

4.3 billion years ago — earliest evidence of liquid water

Planet migration. Nice model. Quaker belt? Kuiper belt? Ice falls inward, planets move outward. Jupiter orbits twice for every one Saturn orbit (2:1 resonance).

(Walsh & Morbidelli, 2010)

(Gomes &al., 2010)

4.1 billion years ago — onset of The Late Heavy Bombardment (LHB), or lunar cataclysm; earliest evidence of biogenic carbon (Bell et al. 2015)..

4 billion years ago — "Cool Early Earth" ends, plate tectonics

3.8 billion years ago — end of The Late Heavy Bombardment (LHB), or lunar cataclysm.

3.5 billion years ago — Noachian period ends on Mars; establishment of the geomagnetic field on Earth, protecting the atmosphere from being swept away by Solar winds.

2.45 billion years ago — the Great Oxygenation Event.

Introduction

Prokaryotes are a paraphyletic group of organisms.



I. Nature of the LUCA



I.a. Individuality of the LUCA



I.a-1.) Discrete LUCA



I.a-2.) Communal LUCAS



I.b. Genomic Base of the LUCA



I.b-1. DNA-based LUCA



I.b-2. RNA-based LUCA



I.c. Cellularity of the LUCA



I.c-1.) Paracellular LUCA

Carl Woese (1998) suggests that the Last Universal Common Ancestor (LUCA) of the three domains may antedate individuation into discrete lifeforms separated by cell membranes, and that the LUCA may have actually been a community of proto-cells with extremely primitive, porous membranes — called "progenotes" (Woese, 1998) — through which, due to pervasive lateral gene transfer (LGT) (Woese, 2002), genetic material was exchanged and propogated itself more-or-less freely. The picture this evokes is one in which, prior to the “Darwininian threshold" (Woese, 2002), the primary, smallest, most irreducible unit of life was less like a modern cell than like a modern chromosome.



I.c-2.) Precellular LUCA

Other authors (e.g. Martin & Russell, 2003; Koonin, 2014) have taken up modifications of Woese's theory which agree that the common ancestor of the Archaea and the Bacteria was a pre-organismal, pre-Darwinian community, but which take this further in hypothesizing that the last common ancestral state (LUCAS) was pre-cellular, and which reassert the importance of Endosymbiotic Theory in understanding the origin of the eukarya. If true, this would mean that the bacteria, whence the mitochondria evolved, and the archaea, a lineage of which went on to become the eukarya, represent two separate evolutions of "true" (discrete, cellular) life. The consequences of this are that (1) the divergence of the two prokaryotic domains from a common ancestor is inextricably interwoven with the origins of life, and (2) that eukaryogenesis represents both a novel convergence of two independently evolved forms of life and a genetic reconvergence of hereditary material that had been separated since before the origin of "true" life.

This view is not universally accepted, with some authors going so far as to adopt literary bravados which (wrongfully) assert that this idea has been abandoned due to common membrane-encoding genes shared by all three domains (e.g., Forterre, 2014), alternate explanations for these shared genes, such as lateral gene transfer (LGT), or even (plausibly, considering the small size and streamlined organization of prokaryotic genomes) convergenet evolution, have not been ruled out.



II. Location of the LUCA



II.a. Terrestrial LUCA



II.a-1.) Darwin's Warm Little Pond



II.a-2.) Prebiotic Ocean



II.a-3.) Deep Sea Vent



II.b. Extraterrestrial LUCA



III. Timing of the LUCA



III.a. Post-Abiogenetic LUCA



III.b. Pre-Abiogenetic LUCA



I.b-1A.) The Terrestrial Origin of Life

Currently there are two primary approaches to the scientific investigation into the origins of life: the replicator-first approach and metabolism-first approach (Anet, 2004). These approaches differ conceptually in hypothesizing either an autocatalytic string of covalently bonded informational molecules at least functionally akin to DNA, or a sequence of chemical reactions a among set of noncovalently bonded molecules that was autocatalytic as whole and thus functionally akin to metabolism (von Meijenfeldt, 2013), as the essential origin of life.

Here it should be noted that the designations "replicator-first" or "metabolism-first" may apply either literally or figuratively. An approach which places primary emphasis on replication over metabolism, for example, may be regarded as a "replicator-first" approach even if it is not literally suggesting that replicators antedate metabolic systems, and vice versa. These are designations of emphasis, not necessarily descriptors of sequence.

(Delaye & Lazcano, 2005)



I.b-1Aα.) Replicator-First Approach

The most crucial entity in and most basal unit of evolution is the replicator (Zachar, 2010).

Since the 1982 discovery of ribozymes (Kruger et al.) proved that RNA had catalytic properties, and could therefore “act both as information carrier and as catalyst” (Alberts et al., 2002), resolved the DNA-protein “chicken & egg” paradox by demonstrating that RNA could act as both “chicken” and “egg” (Bernhardt, 2012; Sankaran, 2013), the replicator-first approach has quite naturally come to be dominated by the “RNA World” hypothesis (von Meijenfeldt, 2013) and this has only been reinforced by the now much-expanded catalytic repertoire of RNA and the import thereof with regard to key cellular reactions (Doudna & Cech, 2002) “which can be viewed as molecular fossils of an earlier world,” meaning we never fully transitioned out of the RNA World (Alberts et al., 2002). Evidence indicating that the common ancestor of the Archaea and the Bacteria possessed an RNA-based genome (Leipe & al., 1999) and only after divergence each separately acquired DNA from DNA viruses, in which DNA first arose (Leipe & al., 1999; Forterre, 2002), has further reinforced this hypothesis.

(Achbergerová & Nahálka, 2011)

(Fegley & Lewis, 1980)

"messy RNA" (Szostak, 2017)



I.a-1Aβ.) Metabolism-First Approaches

Emphasizing ecosystems over discrete organisms and metabolism over reproduction, Eric Smith et al. have characterized the emergence of Earth's biosphere as a sort of geochemical "discharge" resulting from a build-up of energy between the hydrosphere and the lithosphere (Smith, 2007; 2015).

(Smith &al., 2004)

(Copley &al., 2007)

(Morowitz &al., 2008)

Water is necessary to fold proteins (McLain, 2017)

first cells (Szostak, 2017)

(Hazen, 2005)

(Hazen, 2006)

(Hazen & Sverjensky, 2010)

(Hazen & Deamer, 2006)

(Hazen, 2006)

(Deamer &al., 2002)

(Deamer & Monnard, 2006)



I.b-1Aγ.) Problems with a Terrestrial Origin

While the "plausibility" criterion for a given chemical pathway suggested as being involved in prebiotic synthesis generally requires that the chemical environment has to be one which could have plausibly been present on the early Earth, such a criterion ignores that the early Earth isn't the only place that life could have formed. Such is an a priori assumption completely unsupported, and one might go so far as to say contradicted, by all experimental and observational data thus far gathered. The Earth is but one planet among hundreds known and among billions thought to exist in our galaxy alone. Furthermore, there is no particular reason to hypothesize that the generation of life is something which must occur on a planet at all! Especially when one considers how early in the geological record life first began to appear on Earth, other environments such as other Solar planets, exoplanets, planetesimals, asteroids, comets, moons, protoplanetary disks, protostellar nebulae and the stelliferous nebulae (star-forming regions of giant molecular clouds) to which they belong, as well as any interactions between such systems, must all be considered as potential environments for the various stages of prebiotic synthesis, and "plausibility" determined only when a particular chemical pathway has been demonstrated to be likely (or not) in one of such environments. An early-Earth-based "plausibility" criterion is, frankly, an unnatural constraint which ignores the fact that in our universe, no planet is an island.

Many stages of prebiotic synthesis wouldn't have worked out in hydrothermal vent scanrios or on a hot early Earth.

1.

The half-lives of the nucleobases guanine, adenine, cytosine, and uracil are far too short (t½ for adenine and guanine ≈ 1 year; uracil = 12 years; cytosine = 19 days) at the 80-110°C temperatures hypothesized in hydrothermal vent scenarios for the origin of life (based on the preferred temperature ranges of hyperthermophiles, assumed by hydrothermal vent scenarios to be among the oldest extant lineages of living things), and indeed are too unstable at temperatures much above 0°C, to allow for the formation of the first replicators in a reasonably long timespan, indicating a low-temperature origin of life (Levy & Miller, 1998).

2.

RNA hydrolyzes rapidly (Szostak, 2012; part 3), and is especially prone to doing so in hot environments, much to the chagrin of those who favor hydrothermal vent models for the origin of life.

3.

While hydrothermal vent hypotheses imply a hyperthermophilic progenote with an optimal growth temperature (OGT) ≥80°C, which is consistent with thermophilia (OGT=65±15°C) in the last bacterial ancestor as well as the last archaeal ancestor as part of a more-or-less linear progression to the overwhelmingly mesophilic (OGT≤50°C) modern prokaryotic domains, dual phylogenic rRNA and protein analyses show that while both the bacterial ancestor and the archaeal ancestor were thermophilic (OGT=65°C±15°C), the LUCA was mesophilic with an OGT≤50°C (Boussau &al., 2008).

4.

The very first protocells were likely obligate cryophiles with an OGT≈1°C (Szostak, 2012; part 1)

The hydrothermal vent model, though seemingly ruled out, would give us a mathematically elegant and thermodynamically sensible sequence of OGT≥80°C, OGT=65±15°C, OGT≤50°C and a cellular LUCA model gives us a progressive OGT≈0°C, OGT≤50°C, OGT=65±15°C thermotolerance sequence before a general decline to OGT≤50°C with a few modern lineages OGT=65±15°C or even OGT≥80°C, while a precellular LUCA model merely gives us an OGT≤50°C; OGT≥50°C threshold separating the cryophilic-to-mesophilic nucleobases, RNA, LUCA, and protocells, and the thermophilic-to-hyperthermophilic first true lifeforms, followed eventually by diversification into various levels of thermotolerance.

(Szostak, 2012; part 2)

(Sleep, 2010)

Cool Early Earth model.

Here, however, we run into another problem. Water is highly corrosive, and would've been deadly to the first RNA-based replicators (Barras, 2014)

(Ricardo &al., 2004)

(Benner &al., 2012)



I.b-1B.) The Possibility of Panspermia

The hardiness of bacteria features in many lithopanspermia models, the most conservative of which are interplanetary lithopanspermia models, most relavent to we Earthlings in the hypothetical case of Mars-Earth interplanetary lithopanspermia, in which life found its way to Earth from our neighbor, Mars.

We know that bacteria could have been ejected into space by planetary impacts (Stoffler et al. 2006), survive the subsequent rapid acceleration (Mastrapaa et al. 2001), survive exposure to vacuum and high radiation (Saffary &al., 2002; Bucker & Horneck, 1970; Horneck, 1971; Nicholson, &al. 2005), thrive and grow in asteroidal and meteoritic interiors (Mautner 2002), survive re-entry into a planetary atmosphere (blah) and subsequent impact (blah),

Deinococcus radiodurans, first isolated in Corvallis, Oregon, in 1956 (Anderson, &al.)



I.a-1Bα.) Interplanetary Lithopanspermia

Radioresistance in bacteria. Mars fertile for life before Earth.

(Hoch & Losick, 1997)

(Fajardo-Cavazos &al., 1997)

(Matti &al., 2009)

(Clark, 2001)

(Loupkin, 2006)

“So, back to the period of heavy bombardment and with computer simulations you can, you can model what happens when an impact hits a planetary surface. And it's not much different from if you sprinkle Cheerios on a bed [...] and then you smack the surface of the bed, there's a— a sort of a recoil in effect and Cheerios pop upwards. It turns out Mars may have been wet — we've known at some point it had water — and fertile for life before Earth, and at this period of heavy bombardment if it had started life — surely it would've been simple life, as we've no reason to think otherwise — we've learned bacteria can be quite hardy, as I'm sure you know, so we imagine a bacterial stowaway in the nooks and crannies in one of these rocks that are cast back into space. In fact if you do the calculation, there's hundreds of tons of Mars rocks that should that should have fallen to Earth by now, over the history of the Solar system. Maybe one of those rocks carried life from Mars to Earth, seeding life on Earth. My great disappointment would be going to Mars and finding Mars life based on DNA. That it would not've been a separate experiment in life.” — Neil Degrasse Tyson to Richard Dawkins (Dawkins & Tyson, 2016, 6:05-7:24 minutes in)


I.a-1Bβ.) Interstellar Lithopanspermia

Microbe-containing impact ejecta from Earth may be subsequently pulverized by collisions into micron-sized particles that, though large enough to contain colonies of microbial life and shield them from UV radiation, would be small enough to be carried out to the Kuiper Belt via Solar winds eventually to be deposited in the protoplanetary discs of future planetary systems as the Solar system moves through interstellar dust clouds in its course through the Milky Way (Wallis, 2003; Napier, 2003), seeding the Milky Way in just a few billion years, which, considering any Earth-like planet could hypothetically have done the same, makes it highly unlikely that Earth Herself was not a benefactor of such a process (Napier, 2003).



I.b-2.) Independent Origins & Cross-Contamination

It's entirely possible that the reason why so much of the “biological evidence" for panspermia is related to the hardiness of bacteria isn't because all of life on Earth ultimately descends from a Martian ancestor, but because bacterial life specifically evolved on Mars.



I.b-2A.) Trends in Specializations of Prokaryotic Extremophiles

If the Archaea evolved on Earth as the Bacteria were evolving on Mars, , and there was occasional cross-contamination which intensified during the LHB, then we should expect extremophiles which specialize in tolerating spacial extremes, like cold, drouth, low pressure, radioactivity, hyperacceleration and hypergravity, to be found mostly among the Bacteria, while extremophiles among the Archaea should be expected more often to specialize in tolerating decidedly planetary extremes such as heat, high pressure, acidity, salinity, and alkalinity.



I.b-2Aα.) Acidophiles
ARMAN group -Micrarchaeota --Diapherotrites --Parvarchaeota --Aenigmarchaeota --Nanoarchaeota --Nanohaloarchaeota. -Parvarchaeota
Note that for the purposes of the following table, extremophiles adapted to eukaryogenic conditions, such as Acetobacter aceti, which oxidizes ethanol into vinegar, members of the genus Alicyclobacillus, which thrive in oogenic citric acid by contaminating fruit juices, and Helicobacter pylori, which endures human stomach acid, have for obvious reasons not been considered.
Domain Genus & Species OGpH Source Ratio σ (–ρ) ρ %>H0
Archaea
(Baker &al., 2006)
(Fashola &al., 2015)
(Zhang &al., 2015)
Acidianus ambivalens <3 Johnson (1998) 39:25 25/64
(39%)
39/64
(61%)
22%
Acidianus brierleyi <3 Johnson (1998)
Acidianus convivator <4 ()
Acidianus infernus <3 Johnson (1998)
Acidianus manzaensis 1.5-2.5 (Ding &al. 2011)
Acidianus pozzuoliensis <4 ()
Acidianus tengchongensis <4 ()
Acidiplasma aeolicum <4 ()
Acidiplasma cupricumulans <4 ()
Ferroplasma acidiphilum <4 ()
Ferroplasma cyprexacervatum <4 ()
Ferroplasma acidarmanus <3 (Dopson &al.2003)
Halarchaeum acidiphilum <4 ()
Metallosphaera hakonensis <4 ()
Metallosphaera prunae <3 (Johnson 1998)
Metallosphaera sedula <3 Johnson (1998)
Metallosphaera yellowstonensis <4 ()
Picrophilus oshimae 2.2 Rampelotto (2013), Johnson (1998)
Picrophilus torridus 0.06-0.07 Rampelotto (2013), Johnson (1998)
Stygiolobus azoricus <3 (Johnson 1998)
Sulfolobus acidocaldarius <3 (Johnson 1998)
Sulfolobus hakonensis <3 (Johnson 1998)
Sulfolobus islandicus <4 ()
Sulfolobus metallicus <3 (Johnson 1998)
Sulfolobus mirabilis <3 (Johnson 1998)
Sulfolobus neozealandicus <4 ()
Sulfolobus shibatae <3 (Johnson 1998)
Sulfolobus solfataricus 2-4 Johnson (1998), Dopson (2003)
Sulfolobus tengchongensis <4 ()
Sulfolobus thuringiensis <4 ()
Sulfolobus tokodaii <3 Dopson 2003
Sulfolobus yangmingensis <4 ()
Sulfurisphaera ohwakuensis <4 ()
Sulfurococcus mirabilis <4 ()
Sulfurococcus yellowstonensis <4 ()
Sulfurococcus yellowstonii <3 Johnson (1998)
Thermogymnomonas acidocola <4 ()
Thermoplasma acidophilum 1.8 Johnson (1998)
Thermoplasma volcanium <3 Johnson (1998)
Bacteria Acidiphilium spp. <3 (Johnson 1998)
Acidiphilium acidophilum
(Thiobacillus acidophilus)
<3 (Johnson 1998)
Acidiphilium multivorum <3 (Dopson 2003)
Acidithiobacillus albertensis
(Thiobacillus albertis)
<3 (Johnson 1998)
Acidithiobacillus caldus
(Thiobacillus caldus)
<3 Johnson (1998)
Acidithiobacillus ferridurans <4 ()
Acidithiobacillus ferriphilus <4 ()
Acidithiobacillus ferrivorans <4 ()
Acidithiobacillus ferrooxidans
(Thiobacillus ferrooxidans)
<3 Johnson (1998)
Acidithiobacillus thiooxidans
(Thiobacillus thiooxidans)
<3 Johnson (1998)
Acidobacterium capsulatum <3 Johnson (1998)
Acidimicrobium ferrooxidans <3 Johnson (1998)
Acidocella spp. <3 Johnson (1998)
Acidomonas methanolica <3 Johnson (1998)
Alicyclobacillus thermosulfidooxidans spp. <3 Johnson (1998)
Alicyclobacillus thermosulfidooxidans
(Sulfobacillus thermosulfidooxidans)
<3 Johnson (1998)
Bryocella elongata <4 ()
Ferrimicrobium acidiphilum <3 Johnson (1998)
Leptospirillum ferrooxidans <3 Johnson (1998)
Leptospirillum thermoferrooxidans <3 Johnson (1998)
Sulfobacillus acidophilus <3 Johnson (1998)
Telmatobacter bradus <4 ()
Thiobacillus prosperus <3 Johnson (1998)
Thiobacillus acidophilus <4 ()
Thiobacillus organovorus <4 ()
Thiomonas cuprina
(Thiobacillus cuprinus)
<3 (Johnson 1998)
Life (Basel). 2013 Sep; 3(3): 482–485. Published online 2013 Aug 7. doi: 10.3390/life3030482 PMCID: PMC4187170 Extremophiles and Extreme Environments Pabulo Henrique Rampelotto https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187170/
MiniReview Biodiversity and ecology of acidophilic microorganisms D. Barrie Johnson FEMS Microbiology Ecology 27 (1998) 307^317 FEMS Microbiology Ecology Volume 27, Issue 4, Version of Record online: 17 JAN 2006 http://onlinelibrary.wiley.com/doi/10.1111/j.1574-6941.1998.tb00547.x/pdf
Growth in sulfidic mineral environments: metal resistance mechanisms in acidophilic micro-organisms Mark Dopson, Craig Baker-Austin, P. Ram Koppineedi and Philip L. Bond Microbiology (2003), 149, 1959–1970 DOI 10.1099/mic.0.26296-0 http://mic.microbiologyresearch.org/content/journal/micro/10.1099/mic.0.26296-0#tab2
A novel acidophilic, thermophilic iron and sulfur-oxidizing archaeon isolated from a hot spring of tengchong, yunnan, China Jiannan DingI, II, *; Ruiyong ZhangI; Yizun YuII; Decai JinI; Changli LiangI; Yang YiI; Wei ZhuI; Jinlan XiaI, Brazilian Journal of Microbiology Print version ISSN 1517-8382 Braz. J. Microbiol. vol.42 no.2 São Paulo Apr./June 2011 http://dx.doi.org/10.1590/S1517-83822011000200016
An Archaeal Iron-Oxidizing Extreme Acidophile Important in Acid Mine Drainage Katrina J. Edwards, 1,2 * Philip L. Bond, 1 Thomas M. Gihring, 1 Jillian F. Banfield 10 MARCH 2000 VOL 287 SCIENCE p. 1796-1799

I.b-2Aβ.) Alkaliphiles
Domain Genus & Species Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Archaea Halalkalicoccus 16:1 1/16 (6.25%) 15/16 (93.75%) 87.5%
Haloarcula
Halobaculum
Halobiforma
Haloferax
Halorubrum gandharaense
Nanobacterium gregoryi
Natronococcus amylolyticus
Natronococcus jeotgali
Natronococcus occultus
Natronolimnobius
Natronomonas pharaonis
Natronorubrum
Thermococcus alkaliphilus
Thermococcus acidaminovorans
Methanohalophilus
Bacteria (Coming Soon)


I.b-2Aγ.) Barophiles
Domain Genus & Species Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Archaea Pyrococcus abyssi 6:1 1/7 (14%) 6/7 (86%) 72%
Pyrococcus endeavori
Pyrococcus furiosis
Pyrococcus glycovorans
Pyrococcus horikoshii
Pyrococcus woesei
Bacteria Salinicola salarius

(Gareeb & Setati, 2009)
(Pikuta &al., 2017)

I.b-2Aδ.) Hyperthermophiles
Domain Genus & Species Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Archaea Aeropyrum pernix 6:1 1/7 (14%) 6/7 (86%) 72%
Pyrolobus fumaril
Pyrococcus furiosus
Archaeoglobus fulgidis
Methanococcus jannaschii
Stygiolobus azoricus
Sulfolobus acidocaldarius
Sulfolobus islandicus
Sulfolobus metallicus
Sulfolobus neozealandicus
Sulfolobus shibatae
Sulfolobus solfataricus
Sulfolobus tengchongensis
Sulfolobus thuringiensis
Sulfolobus tokodaii
Sulfolobus yangmingensis
Methanopyrus kandleri
"Strain 121"
Bacteria Aquifex aeolicus
Geothermobacterium ferrireducens
Theromotoga maritima


I.b-2Aε.) Totals for Planetary Extremes
Extreme Domain Number Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Acidity Archaea 18 18:7 7/25 (28%) 18/25 (72%) 44%
Bacteria 7
Alkalinity Archaea 6 16:1 1/16 (6.25%) 15/16 (93.75%) 87.5%
Bacteria 1
Salinity Archaea
Bacteria
High Pressure Archaea 6 6:1 1/7 (14%) 6/7 (86%) 72%
Bacteria 1
Heat Archaea 18 6:1 1/7 (14%) 6/7 (86%) 72%
Bacteria 3
Total Archaea
Bacteria


I.b-2Aζ.) Radioresistant Prokaryotes
Domain Genus & Species Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Archaea Pyrococcus furiosis 1:4 1/5 (20% 4/5 (80%) 60%
Haloferax volcanii
Natrialba magadii
Thermococcus gammatolerans
BacteriaBacillus subtilis
Bacillus atropheus
Bacillus thuringiensis
Bacillus cereus
Bacillus megaterium
Deinococcus radiodurans
Escherichia coli
Rubrobacter sp.
Achromobacter sp.
Acinetobacter sp.
Alcaligenes sp.
Enterococcus sp.
Micrococcus sp.
Pseudomonas sp.
Staphylococcus sp.
Streptococcus sp.

(Abrevaya &al., 2011)
(Bucker & Horneck, 1970)
(Horneck, 1971)
(Nicholson, &al. 2005)

I.b-2Aη.) Xerophilic Prokaryotes
Domain Genus & Species Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Bacteria Bacillus subtilis 2:0 0/2 (0%) 1/1 (100%) 100%
Escherichia coli


I.b-2Aη.) Cryophilic Prokaryotes
Domain Genus & Species Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Bacteria Bacillus subtilis 2:0 0/2 (0%) 1/1 (100%) 100%
Escherichia coli


I.b-2Aθ.) Totals for Spacial Extremes
Extreme Domain Number Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Radioactivity Archaea 4 4:1 1/5 (20%) 4/5 (80%) 60%
Bacteria 20
Hyperacceleration / Hypergravity Archaea
Bacteria 2
Low Pressure Archaea
Bacteria
Cold Archaea
Bacteria
Drouth Archaea 0 2:0 0/2 (0%) 1/1 (100%) 100%
Bacteria 2
Total Archaea
Bacteria


I.b-2Aι.) Totals for Prokaryotic Extremophiles
Extreme Type Ratio σ(%)<(ρ=100%) ≈ ρ ≈ %>H0
Acidity Planetary 18:7 7/25 (28%) 18/25 (72%) 44%
Alkalinity 16:1 1/16 (6.25%) 15/16 (93.75%) 87.5%
Salinity
High Pressure 6:1 1/7 (14%) 6/7 (86%) 72%
Heat 6:1 1/7 (14%) 6/7 (86%) 72%
Radioactivity Spacial 1:4 1/5 (20%) 4/5 (80%) 60%
Hyperacceleration / Hypergravity
Low Pressure
Cold
Drouth 2:0 0/2 (0%) 1/1 (100%) 100%


I.b-2A.) Problems with Independent Origins
"What we need is a second sample of life. We have only one at present. It would be- it would a disappointment, as you say, to find life based on DNA, or at least life on Mars based on the same DNA code. [You can] just about imagine DNA evolving twice, but you couldn't imagine the same, uh, four-letter code, um, uh, evolving twice." (Richard Dawkins to Neil Tyson, Dawkins & Tyson, 2016, 7:30-7:57 minutes in)

Since modern RNA can be used as a template to synthesize DNA, with the uracil in RNA matching the thyamine in DNA, it is entirely possible that what Dawkins refers to as “the same four-letter code" in DNA could have evolved twice, so long as the two DNA codes were derived from a common RNA code. This could be said to be dodging the issue of how DNA evolved twice in the same way that (most) panspermia hypotheses dodge the issue of how life began. This therefore begs the question: How could the same four-letter RNA code have evolved twice? The most obvious solution is that the same four-letter RNA code couldn’t have evolved twice, but must have come from a common RNA-based ancestor. The independently-derived DNA codes could thus be compatible with one another so long as the RNA codes on Earth and Mars had not yet greatly diverged since their common ancestor. That is to say, if in the early Solar system there was RNA-based life on both Mars and Earth, and these lifeforms (or quasi-lifeforms) were still very closely related and compatible with one another, and DNA originated roughly in this time period, independently on both worlds, then the DNA on either planet very well may have been compatible with the other simply by virtue of having been synthesized by nearly identical RNA codes.

Furthermore, there is, as noted earlier evidence indicating that the common ancestor of the Archaea and the Bacteria possessed an RNA-based genome (Leipe & al., 1999) and only after divergence was DNA acquired separately in the two lineages, possibly from DNA viruses in which DNA first arose (Leipe & al., 1999; Forterre, 2002).

Regardless, whether DNA evolved once, on either Earth or Mars, or twice, separately in the ancestors of the Archaea and the Bacteria, the fact that Archaea and Bacteria can experience LGT with one another and presumably would have been able to do so far more easily in the distant past, leaves us with the inescapable reality that there must have been a common origin for both of these groups. The Archaea and the Bacteria simply could not have evolved entirely independently ex nihilo.



I.b-2B.) Alternative Explanations for Apparent Evidence of Independent Origins

The apparent "biological" evidence for independent origins, which mainly has to do with various bacteria having adaptations which confer upon them survivability when exposed to spacial conditions as opposed to the archaea, may be explainable by known conditions in Earth's past.

To space and back during the LHB (Wells, &al., 2003).

Natural fission reactors (Davis &al., 2014) representing a “critical event” (Gauthier-Lafaye &al., 1996) possible formation of the Moon by a nuclear explosion at Earth's core-mantle boundary (CMB) (de Meijer &al., 2010).

Another possibility is that Earth and Mars were both seeded by a common source of biological life.



I.b-3.) The Protoplanetary Origin of Life

The earliest stages of life on Earth very likely antedate the Earth Herself. This idea has been variously referred to as “molecular panspermia", “quasi-panspermia", or “pseudo-panspermia".

"Essential to the spontaneous origin of life was the availability of organic molecules as building blocks. The famous ‘prebiotic soup’ experiment by Stanley Miller (Miller 1953, Miller-Urey experiment) had shown that amino acids, the building blocks of proteins, arose among other small organic molecules spontaneously by reacting a mixture of methane, hydrogen, ammonia and water in a spark discharge apparatus. These conditions were assumed to simulate those on the primitive Earth. Already in 1922 Oparin had proposed that the early Earth had such a reducing atmosphere (in his classic ‘The Origin of Life’ from 1936 he expanded on these ideas). Observations of Jupiter and Saturn had shown that they contained ammonia and methane, and large amounts of hydrogen were inferred to be present there as well (it is now known that hydrogen is the main atmospheric component of these planets). These reducing atmospheres of the giant planets were regarded as captured remnants of the solar nebula and the atmosphere of the early Earth was assumed by analogy to have been similar." -- The Origin of Life by Albrecht Moritz

(Moritz, 2010)

"Indigenous purines and pyrimidines have been detected in several carbonaceous chondrites. The pyrimidine uracil and the purines adenine, guanine, xanthine, and hypoxanthine (Stoks & Schwartz 1979, 1981) were detected in the CM carbonaceous chondrites Murchison and Murray, as well as in the CI meteorite Orgueil, in total concentrations of about 1.3 parts per million (ppm). Upper limits exist (detection limit of 0.01 ppm) for the concentrations of thymine and cytosine, as well as other heterocyclic compounds, in the Murchison meteorite (van der Velden & Schwartz 1977)."

(Peeters &al., 2003)

(Zita &al., 2008)

(Martins &al., 2008)

(Ehrenfreund & Cami, 2010)

(Ziurys, 2008)

(Coggins & Powner, 2017)

The conditions of the Miller-Urey experiments more closely resemble the conditions of the Solar nebular than the conditions of the primordial Earth (Hill & Nuth, 2003).

The purine bases adenine and guanine have been detected in meteorites, although the only pyrimidine-base compound formally reported in meteorites is uracil (Stoks & Schwartz, 1979), however cytosine cannot be ruled out (Shapiro, 1998; Peeters &al., 2003; Martins &al., 2006) and ultraviolet irradiation of low-temperature ices (the dominant phase of H2O in cold astrophysical environments is ice, and most ices in such environments are H2O-rich) has been shown to produce not only amino acids, quinones, and amphiphiles, but have also, with the introduction of pyrimidine, been shown to produce uracil (Nuevo &al., 2009), cytosine, and even thiamine, though the abiotic synthesis of thiamine is less straightforward compared to other pyrimidine-base compounds (Sandford &al., 2014). (That this would logically make the prebiotic synthesis of RNA easier than that of DNA could explain why RNA has a larger repertoire of functions than does DNA in modern cells.) Additionally, ribose and related sugars have been produced experimentally in interstellar ice analogues (Meinert &al., 2016).

Cytosine can be synthesized from cyano-acetylene and cayanate, this is unlikely to have occured in acqueous media as cayanate is rapidly hydrolized into CO2 and NH3.

Cyano-acetylene is an abundant interstellar molecule and can by produced by a spark discharge in a CH4/N2 environment.

hydrolysis of cyanoacetylene leads to cyanoacetaldehyde

reaction of cyanoacetaldehyde with urea produces cytosine in 30-50% yields

Hydrolysis of cytosine leads to uracil

(Robertson & Miller, 1995)

(Pudritz, 2016)

(Sandford, Bera &al., 2014)

(Kuga &al., 2015)

What all of this means is that hypothetical geochemical pathways for the production of key organic compounds here on Earth, though interesting, are completely superfluous, since the biochemical building blocks of life were already being produced astrochemically before the formation of the Earth. Occam's razor therefore dictates that such geochemical hypotheses for the prebiotic synthesis of organic compounds should be regarded as irrelevant to the origin of life problem.

Clear liquid turns brown as amino acids form peptides. Jennifer Blank. Experiment.

Amino acids + impact = peptides (Blank & al. 2001)



I.b-4.) Synthesis: Molecular Panspermia & Subsequent Mars-Earth Interplanetary Lithopanspermia

Rather than an “RNA world" on either Earth or Mars, the Last Universal Common Ancestor (LUCA) may have lain in the “RNA cloud" of the protoplanetary Solar nebula. The early RNA-based replicons wouldn't necessarily have been “life" in the modern sense of the word, and might have lacked lipid cell membranes as some researches (cite) have suggested for the LUCA even in purely terrestrial models, with the development of cell membranes being an example of parallel evolution. If the development of more modern features of life (or rather, the features we associate with “true life") such as cell-membranes, and possibly even thymine-using nucleic acid, occured separately on Earth and Mars, the result would be two independent evolutions of “true life" that would appear to be very closely related to one another by having shared a relatively recent amembranous RNA-based ancestor. DNA and cell membranes may have evolved separately in parallel simply because this was the most sensible way for the LUCA to respond to the two nearly identical new environments of early Earth and early Mars as the Solar nebula accreted into the terrestrial planets. (This also means it may not be a futile endeavor to search for past-life on Venus, as the environment of early Venus was very much like the environment of early Earth and early Mars, and a sort of “Bacteria from Mars, Archaea from Venus" scenario, with the eukarya developing on Earth, being most closely related to Venereal/Archaeal life but having incorporated Martian/Bacterial life in the form of mitochondria, isn't difficult to envision, either).

(Belbruno, 2012)

So while the first and most obvious objection to the idea of independent origins should be that all life on Earth appears to have descended from a common ancestor, it does not necessarily follow that all life on Earth must have originated on a single planetary body — this objection could only seem reasonable to researchers who wrongly assume that the environments of the planets have always been as isolated from one another as they presently appear to be, which is simply not the case. The early Solar system was a chaotic place; organic molecules were likely already present when the material that would later accrete into the planets were but a diffuse and relatively (compared to today) homogenous gas cloud, which “curdled" gradually into something like a vast asteroid field, the rocky, protoplanetary bodies growing larger and fewer in number as the material accreted until the planets we are now familiar with arose out of the chaos. When the planets were smaller and surrounded by yet-to-be-accreted debris, impacts would have logically been far more frequent, and the smaller sizes of the proto-planetary bodies relative to the modern planets would've meant that lower-speed impacts — and therefore a larger proportion of the impacts which occured — were kicking impact debris back into space.



II.b-1.) Prokaryotic Multicellularity

(Ereskovsky &al., 2013)


II.b-1A.) Bacterial Multicellularity

Bacterial multicellularity can be grouped into three general categories (Lyons & Kolter, 2015):

☣ Filaments —
☣ Aggregates —
☣ Biofilms —
☣ Swarms —
☣ MMPs (multicellular magnetotactic prokaryotes) —



II.b-1B.) Archaeal Multicellularity

(Fröls, 2013)

(Orell &al., 2013)



Works Cited



Carl Woese. The universal ancestor. Proc Natl Acad Sci USA v.95(12); 1998 Jun 9 PMC22660 1998 Jun 9; 95(12): 6854–6859.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC22660/



Carl R. Woese. On the evolution of cells. Proc Natl Acad Sci U S A. 2002 Jun 25; 99(13): 8742–8747. Published online 2002 Jun 19. doi: 10.1073/pnas.132266999
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC124369/

References