Chemical Evolution across Space & Time - American Chemical Society

Chapter 16

The RNA World Scenario for the Origins of Life 1

James P . Ferris and John W . Delano

2

Downloaded by RUTGERS UNIV on May 30, 2018 | https://pubs.acs.org Publication Date: February 15, 2008 | doi: 10.1021/bk-2008-0981.ch016

1

Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180 Department of Earth and Atmospheric Sciences, The University at Albany, Albany, NY 12222

2

RNA was proposed to have been the most important biopolymer in the first Life on Earth in 1968 by Crick and Orgel. The finding by Cech and Altman in 1982 that RNA can catalyze reactions as well as store genetic information supported this hypothesis. More recent experimental findings concerning this postulate for the origins of life will be discussed.

Introduction "How and where did life on Earth arise" was highlighted as one of 25 top science questions in 2005 in Science (1) and one of the six top questions in "What Chemists Want to Know" in 2006 in Nature (2). Origins of life studies are one of the more interdisciplinary fields in science. It requires that astronomers, physicists, geologists, chemists and biologists collaborate to determine the sources and reactions of organic compounds that initiated the first life. Some of the areas of interaction in these investigations include: the search for interstellar organic compounds by astronomers; physicists modeling the formation of solar systems; geologists investigating the organic and inorganic compounds in meteorites and in ancient rock formations on Earth; chemists © 2008 American Chemical Society Zaikowski and Friedrich; Chemical Evolution across Space & Time ACS Symposium Series; American Chemical Society: Washington, DC, 2008.

293


294 simulating the reactions of organics in simulated prebiotic environments and analyzing the organics in meteorites; and biologists studying ancient life forms to gain insight into the nature of early life on Earth. Data from these and other sources are central to the development of scenarios of the steps leading to the compounds that initiated the first life on Earth. At the time of this writing there is no hypothesis that is generally accepted in the scientific community that explains how life may have originated on Earth. Actually it is not known if life originated on Earth or if it was delivered here from some other location like Mars. Meteorites have been found on Earth that clearly came from Mars. It is likely that they were blasted off Mars by the impacts of large meteorites and traveled in highly elliptical orbits that eventually intersected the Earth's orbit. The high levels of radiation in the interplanetary medium suggest that life may not have survived a lengthy trip to Earth, a finding that supports the view that life originated on Earth, but does not totally preclude the possibility that Earth was seeded with life from another source. In the study of the origin of life one must decide what are the most important properties of life. One answer is catalysis and replication with change. Information storage is essential so that the early life can be maintained by replication while change is required so the simplest life can evolve to the more efficient life forms we have on the Earth today. This simple model does not require a complex structure for the first life. A group of replicating polymers bound to the surface of a mineral, dubbed "life on the rocks" by Leslie Orgel, would do the trick (5). A more complex system is favored by those who propose that the first life must be able to generate the compounds essential for life (metabolism) and this life is protected from the environment inside a "container", a structure similar to a cell membrane, so the integrity of the life can be protected from a changing environment. The spontaneous formation of a metabolic system appears to have been too complicated to occur on the primitive Earth, so we favor the "life on the rocks" scenario.

The RNA World The RNA world scenario may provide a route to the origin of life. In this hypothesis it is claimed that RNA was the key biopolymer in the first life because RNA can serve both as a catalyst as well as repository of genetic information (4, 5). Later the RNA world evolved into the protein/DNA world that is the basis of life on Earth today. Evolution of the RNA world to the protein/DNA world was likely because protein is a more versatile catalyst than RNA. DNA is a more stable structure than RNA and hence is a better storehouse

Zaikowski and Friedrich; Chemical Evolution across Space & Time ACS Symposium Series; American Chemical Society: Washington, DC, 2008.

295 of genetic information. The basic structure of RNA is similar to that of DNA except it has an extra hydroxyl group in the 2'-position on its 5-membered ring and a uracil in place of the thymine (Figures la and lb). Ο O-p-o-i

'


OH

π Βι Uj.°5j OH OH a.

Ο Ό-Ρ-Ο-i η , ' ±
4 OH OH b.

OH

N ^

o o o H il il ο O-P-O-P-O-P-O-i ο f OH OH Λ \§'°2^ VOH - eOH r Η

O

N

^

N

H

H

2

0

?

0

H

0=P—Ο-,

O ^ N '

Χ

ι

OH

NH,

OH

Figure 1. Structures of RNA and DNA (a) ribonucleic acid (RNA) monomers with B=z adenine, guanine (G), cytosine (C) and uracil (U), (b) deoxyribonucleic acid monomer with B= adenine (A), guanine (G), cytosine (C), thymine (T), and (c) 5 '-triphosphate of RNA (d) the structure of a 4 mer of RNA.

The synthesis of RNA and DNA in biological systems requires the presence of the high-energy triphosphate-activating group at the S'-position of the monomers (Figure lc) because hydrolysis of the phosphodiester bond of RNA and DNA is favored over its formation in the presence of water. Hence, the prebiotic synthesis of RNA also requires an activating group on the 5'-phosphate of the RNA monomers for the synthesis to occur. Imidazole and 1-methyladenine are used as activating groups in our proposed prebiotic synthesis of RNA oligomers. These activated nucleotides are abbreviated ImpN and MeadpN, respectively where Im is imidazole and Mead is 1-methyladenine. A tetramer of RNA, linked by 3', 5'-phosphodiester bonds is shown in Figure 1(d).


296

Status of the Prebiotic Synthesis of RNA Monomers

Purine and Pyrimidine Bases Meteorites from the asteroid belt are a potential source of some of the purine bases present in RNA. As asteroids travel in their orbits between Mars and Jupiter they collide with each other and pieces are broken off that vary in size from large bodies (potential meteorites) to dust particles. If the energy of the collision is great enough, this material is propelled out of its orbit into the interplanetary medium and some of the material eventually reaches the Earth. Approximately 10 kg of asteroidal material reached the primitive Earth's surface (6). This corresponds to a layer of material weighing 2 χ 10 kg/m if spread uniformly over the surface of the Earth. The carbon content of the soluble organics present (1%) is equivalent to a layer of carbon compounds 25 m thick on the primitive Earth. Since meteorites contain about 1 ppm of purines and pyrimidines, then about 10 kg of these compounds were on the primitive Earth. The purine and pyrimidine bases may have also been formed on the primitive Earth. The so-called "HCN polymer", formed by the self-condensation of liquid HCN or concentrated solutions of HCN (7), yields purines, pyrimidines and amino acids when hydrolyzed (Figure 2) (8).


21

6

2

15

Jk HCN^^CNpolymer-l^/Y^N

2

m

ο ΗΛ

C)

N^hT Adenine

ο ^

Uracil

ο

0 H ^ O H

ή ρ

C

0

0

5-Hydroxy uracil Orotic acid

H

N

4, 5-Dhydroxypyrimidine

Figure 2. Formation of adenine and pyrimidines by hydrolysis of the "HCN polymer".

An alternative route to purines is via the self-condensation of dilute solution (>0.01 M) of HCN at pH 9 to a tetramer of HCN. Photolysis of the HCN tetramer yields 4-aminoimidazole-5-carbonitrile (9JO). This aminoimidazole reacts with HCN to generate adenine. Other purine bases are also formed by the reaction of the aminoimidazole carbonitrile with other one or two carbon compounds (8). Pyrimidines are also formed by the reaction of cyanoacetylene and cyanoacetaldehyde with guanidine, cyanate and urea under a variety of reaction conditions (//, 12). The observation of several potential sources of purines and


297

HCN Tetramer

4_eyano- 5-aminoimidazole

Adenine

Figure 3. Adenine is formed stepwise by the reaction of 0.1M HCN.


pyrimidines suggests that they were likely to have been present on the primitive Earth.

HCiCCN o r

+

H 0=ÔCH CN 2

2

NC

N

H

A NH

2

HN

,?

HN-^S H 0

H

HN M, ; ,CH HN ^ N Η

2

I

2

NH

2

c

H N

X

cytosine Uracil

Ν

J)

H

Figure 4. Pyrimidines are formedfrom cyanoacetylene or its hydrolysis product cyanoacetaldehyde.

Ribose The sugar ribose is the backbone of RNA monomers (Figure la). Initially it was proposed that the self-condensation of formaldehyde was a prebiotic route to ribose. This pathway is out of favor because about thirty other sugars besides ribose are formed in this reaction with the yield of ribose being in the 1-2% range (13). Since most of these sugars have similar reactivity, it is not clear why the ribose in this mixture would react selectively with purines and pyrimidines to form nucleosides. Several new routes to ribose have been proposed in the last 15 years. Of particular interest are convergent syntheses that result in the formation of the four pentoses of sugars, one of which is ribose (Figure 5). In these syntheses it is possible to form the pentoses from sugars that have either lower or higher molecular weight than ribose (14, 15). Other prebiotic ribose syntheses have been reported (16, 17). The variety of routes to ribose suggests that it was present on the primitive Earth.

Nucleosides, Nucleotides And Activated Nucleotides A major problem with the RNA world scenario is the absence of a convincing prebiotic synthesis of nucleosides (Figure 1). Dry heating of a


298 C H = 0 MgtOHk/PbCr^

ribose, arabinose, lyxose and xylose in about equal amounts

2


Figure 5. Metal ion catalysis of the conversion offormaldehyde to pentose sugars.

mixture of ribose, sea salt and adenine gives a 4% yield of the β-anomer of adenosine, and with guanine a 9% yield of the β-anomer of guanosine (18). aanomers are among the other products (Figure 6a). No nucleosides were formed when mixtures of the pyrimidines, uracil, cytosine and thymine, were reacted together with ribose under the same conditions used to generate nucleosides from purine bases (18). The absence of a convincing prebiotic synthesis of nucleosides is a deficiency of the RNA world scenario for the origin of life.

c

100° a. Ribose + Adenine* MgCI or Sea Salts

»-~2% β-Adenosine and ~2% α-Adenosine

2

HO-,

η

HO-

OH O H *

OH OH

oc-anomer

β-anomer

Figure 6. a-and β-Adenosine formation (a) by dry heating adenine with salts and ribose with the formation of (b) a- and β-anomers among other products.

The formation of nucleotides from nucleosides was more successful. Heating uridine in the presence of N H H P 0 with an excess of urea yields uridine nucleotides that have phosphate groups at the 2', 3 or 5'-positions of nucleosides together with lower yields of products that have two or more attached phosphate group (19). When the mineral struvite (MgNH P0 H 0) is used in place of N H H P 0 in the synthesis a 25% yield of the 5'-pyrophosphate of uridine is obtained. (20) 4

2

4

5

4

4

2

4

2

4

Uridine (excess) + Phosphate + N H H P 0 4

2

4

^

* pU, Up, cyclic Up, pUp and cyclic pUp

Figure 7. Phosphorylation of uridine to nucleotides


299

Catalysis of RNA Oligomer Formation

Metal Ion Catalysis 2+

Both lead (Pb ) and some lead minerals catalyze the formation of up to 10 mers starting from the 5'-phosphorimidazolide of adenosine (5'-ImpA). (21, 22) The oligomers are linked mainly by 2', 5'-phosphodiester bonds. Uranyl ion (U0 ) is a more efficient catalyst of the reaction of the activated nucleotides of A, U , and C. (23) Chain lengths 16, 10, and 10 monomer units (mers), respectively are formed that are linked mainly by 2', 5'-phosphodiester bonds. When the Pb reaction is performed in the eutectic phase of water at -18° C for 20-40 days, oligomers as long as 17 mers are formed in yields of 80-90% (24, 25). Most of the water is present as ice crystals so the higher yields may be due to the slower rate of hydrolysis the imidazole activating groups at the lower temperature and/or the higher concentrations of the activated monomers in the liquid phase. 2+

2


2+

Montmorillonite Catalysis The observation that montmorillonite clay was a weak catalyst for the formation of the 2', 3'-cyclic phosphates from 3'-nucleotides (26) prompted our investigation of the formation of RNA oligomers from 5'-imidazole activated nucleotides. Initial studies demonstrated that some montmorillonites were "excellent" catalysts for oligomer formation if they were converted to the Na form by the procedure of Banin (29, 30). In this procedure the montmorillonite is treated with cold HC1 to generate the acidic form of the montmorillonite and then converted to the Na form by treatment with NaCl. Oligomers that contained up to 10 mers were formed from ImpA (Figure 7a) (27, 28). It was possible to attain 40-50 mers by the reaction of ImpA with a decameric primer in the presence of montmorillonite in a "feeding" reaction (32,33). The latest advance in the formation of long oligomers is the synthesis of 40-50 mers in one day using 1-methyladenine as the activating group and a modified reaction procedure (Figure 7b)(52, 33). This is important because it is now possible to generate large amounts of the long oligomers so it easier to probe their properties. Most of the RNA in contemporary life is linked by 3', 5'-phosphodiester bonds while the oligomers formed by montmorillonite catalysis have both 3', 5'and 2', 5'-phosphodiester bonds (Figure 8). The proportions of each type of +

+


300 NH

a

Ο - N^N-P-O—ι

2

( Μ J ^ Ν

rs

10 mer

> Λ

"Feeding" Montmorillonite *- 2-50 mers MgCI NaCI, pH 8 12-14 days 2

OH OH NH 2 ΙΝΠ2 Ο II

b. N ^ N — P - O - i


W

0

H N-3,900 million years (i.e., Hadean Eon) have provided geochemical constraints that bear importantly on whether catalytically active montmorillonites would have been present on the ancient Earth, and thereby played a role in the formation of biopolymers. For example, as previously noted, the catalytically active Wyoming-type' montmorillonites are the alteration products of explosive, airfall deposits of volcanic debris having granitic compositions. The Earth at 4,4004,500 million years in the past may have already developed a significant mass of continental crust having a broadly granite-like composition (55). If the tectonic processes that generated that continental crust in the Hadean are similar to those that are known to have operated on the Earth for at least the last 3,000 million years, the Earth appears to have arrived at its current, large-scale chemical zonation (i.e., crust, mantle, core)

Chemical Evolution across Space & Time - American Chemical Society

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