H00102--00A, Front mat Genesis
Page 40
the mineral surface—an essential characteristic of surface life. Otherwise,
the metabolites would break free and be lost forever in the dilute ocean.
In this regard, a word about nomenclature is in order. The molecules
that form the citric acid cycle are all acids in their electrically neutral state: acetic acid, pyruvic acid, oxaloacetic acid, and so on. In solution, however,
these molecules typically give up a hydrogen atom to become negatively
charged molecules called acetate, pyruvate, oxaloacetate, and so on. For this
reason the citric acid cycle is sometimes called the citrate cycle.
p. 211
What do experiments: Cody et al. (2001b).
p. 212
Cody found evidence: Cody et al. (2001b); see also Cody
284
GENESIS
(2004). They observe the reaction of 1-nonene (a 9-carbon molecule) with
nickel sulfide in a formic acid solution to 10-carbon carboxylic acids. This
reaction implies that a similar beta-pathway reaction of 3-carbon propene
to form 4-carbon methyl acrylic acid is possible.
p. 212
And perhaps someday: The lack of experimental verification
of many chemical steps in the Iron–Sulfur World hypothesis remains a point
of criticism (de Duve and Miller 1991). In particular, the relative instability
of oxaloacetate, which tends to decarboxylate rapidly, poses a significant
challenge to the development of a reductive citric acid cycle before enzymes
(Lazcano and Miller 1996).
p. 213
Michael Russell and Allan Hall: Russell and Hall (Russell et al.
1993, 1994; Russell and Hall 1997, 2002). An intriguing feature of the Russell
and Hall model is its reliance on mineral phases with iron and/or nickel in
more than one valence state: Mackinawite [(Fe,Ni)
S] is proposed as the
1+ x
principal membrane sulfide, whereas greigite (Fe S ) and violarite (FeNi S )
3 4
2 4
serve the role of catalysts. The structures of these minerals bear striking re-
semblances to the structures of Fe–Ni–S clusters at the core of key metabolic
enzymes, including ferredoxins and CO dehydrogenase (Russell and Hall
2002). See also Adams (1992), Beinert et al. (1997), Rawls (2000), Doukov et
al. (2002), and J. W. Peters (2002) for descriptions of a variety of metal–
sulfur clusters in enzymes.
p. 213
“flat life”: Wächtershäuser’s Iron–Sulfur World hypothesis, for
example, relies on two-dimensional growth across a pyrite surface. A num-
ber of other authors have speculated on the possibility of flat life, including
E. Smith and Morowitz (2004). For a critique of this proposal, see de Duve
and Miller (1991) and Wills and Bada (2000, p. 138).
16
THE RNA WORLD
p. 215
“It is generally believed . . .”: Joyce (1991, p. 391).
p. 215
classic 1968 paper: Orgel (1968, p. 381) writes, “It is argued
that the evolution of the genetic apparatus must have required the abiotic
formation of macromolecules capable of residue-by-residue replication. This
suggests that polynucleotides were present even in the most primitive ances-
tors of contemporary organisms.”
p. 216
a messy business: Fox and Harada (1958).
p. 216
“I must confess . . .”: Orgel (1986, p. 127).
p. 216
RNA ribozymes: Early work on ribozymes includes Kruger et
al. (1982), Guerrier-Takada et al. (1983), Bass and Cech (1984), Zaug and
Cech (1986), Been and Cech (1988), and Altman et al. (1989). Subsequent
NOTES
285
work has produced ribozymes that accomplish a wide range of catalytic func-
tion (see, e.g., Cech 1990, 1993; Noller et al. 1992).
In fact, the theoretical papers of Woese (1967), Crick (1968), and Orgel
(1968) all anticipated the discovery of ribozymes by postulating the exist-
ence of genetic molecules that act as catalysts.
p. 217
RNA World: The term “RNA World” was proposed in a short
note by Harvard chemist Walter Gilbert (1986), in the same year that Alberts
(1986) and Lazcano (1986) proposed that catalytic RNA preceded DNA. Gil-
bert postulated the RNA World as a step in life’s development when RNA
molecules were sufficient “to carry out all the chemical reactions necessary
for the first cellular structures.” These ideas received much subsequent elabo-
ration, for example by Orgel (1986), Joyce et al. (1987), Joyce (1989, 1991,
1996), Biebricher et al. (1993), Lehman and Joyce (1993), and Joyce and
Orgel (1993).
p. 217
study of ribosomes: Ban et al. (2000) and Nissen et al. (2000).
Nobelist Thomas Cech (2000) contributed a high-profile analysis of this
work, entitled “The ribosome is a ribozyme.”
Jack Szostak writes: “You could write a book on just the intrigue and
controversy and personalities involved in determining the structure of the
ribosome—arguably the most important ‘molecular fossil’ of modern cells
(all right, at least comparable to the citric acid cycle).” [Jack Szostak to RMH,
21 August 2004].
p. 218
called coenzymes: Lehninger et al. (1993) provide an overview
of the functions of coenzyme-A and other coenzymes that incorporate
nucleotides.
p. 218
“riboswitches”: Winkler et al. (2002, 2004) and Sudarsan et al.
(2003).
p. 218
uses rather simple molecules: e.g., Lehninger et al. (1993).
p. 219
RNA nucleotides, by contrast: RNA nucleotides are themselves
assembled from three smaller molecules: the 5-carbon sugar ribose, one of
four different cyclic compounds called bases, and an orthophosphate (PO )
4
group. Bases have been synthesized in a variety of plausible prebiotic experi-
ments, including S. L. Miller’s (1953) original experiments and in many sub-
sequent studies (Oró 1960, 1961a; Sanchez et al. 1967; Ferris et al. 1978;
Robertson and Miller 1995; Shapiro 1995; and Hill and Orgel 2002). For an
excellent overview of this progress, see S. L. Miller and Lazcano (2002, pp.
92-100).
The synthesis of the 5-carbon sugar ribose, a relatively unstable mol-
ecule, is more difficult, though it has been produced in modest yields by the
reaction of formaldehyde—the so-called formose reaction (Butlerow 1861,
Reid and Orgel 1967, Cairns-Smith et al. 1972, Shapiro 1988, and Schwartz
and de Graaf 1993). Interestingly, Ricardo et al. (2004) report that borate
286
GENESIS
minerals may stabilize ribose preferentially, and Springsteen and Joyce
(2004) find that ribose passes through lipid membranes an order of magni-
tude more easily than other 5-carbon sugars. These effects may have en-
hanced the prebiotic selection of ribose.
Equally problematic is a reliable prebiotic source of orthophosphate
(Weber 1982, Westheimer 1987, Yamagata et al. 1991, de Graaf et al. 1995, Lazcano and Miller 1996, Kornberg et al. 1999, Kornberg and Fraley 2000,
and de Graaf and Schwartz 2000).
Even more daunting is a viable mechanism to a
ssemble the three com-
ponents—base, sugar, and phosphate—into a nucleotide. Pitsch et al. (1995)
reported successful synthesis of sugar phosphates, but ribose and bases are,
in general, not stable under the same set of conditions (Joyce 1989, Joyce
and Orgel 1993, Lahav 1999, and Zubay and Mui 2001). Wills and Bada
(2000, p. 131) conclude: “It is very difficult to imagine how even the building
blocks of RNA could have arisen by themselves, much less chains of RNA
constructed from the building blocks.”
p. 219
catalytic RNA sequences: Even if individual nucleotides could
be synthesized in abundance, there is no known way to induce them to poly-
merize in a realistic prebiotic environment. A number of experiments have
demonstrated the spontaneous formation of nucleotide–nucleotide bonds,
for example, in the presence of clay minerals (Ferris et al. 1988, 1996; Ferris
and Ertem 1992, 1993; and Ertem and Ferris 1996, 1997), but these nucle-
otides were “activated”—chemically altered to enhance their reactivity.
p. 219
Biologists seem reasonably confident: An extensive half-cen-
tury of literature, commencing with the work of George Gamow (1954),
considers the origin of the DNA-Protein world and the genetic code. This
topic postdates the chemical origin of life and thus is beyond the scope of
this book. For reviews, see de Duve (1995a, Chapter 6), Lahav (1999, Chap-
ter 17), Maynard-Smith and Szathmáry (1999, Chapter 4), and Wills and
Bada (2000, Chapter 7). Hayes (2004) provides a concise survey of the origin
of the genetic code.
p. 219
intractable gap: Leslie Orgel (2003, p. 213) states, “I believe
that it is very unlikely that RNA did arise prebiotically on the primitive
Earth.” S. L. Miller (1997, p. 167) echoes that belief: “RNA is an unlikely
candidate.”
17
THE PRE-RNA WORLD
p. 221
“I’ve been waiting . . .”: [Simon Nicholas Platts to RMH, 27
May 2004]
p. 221
“Identifying the first . . .”: S. L. Miller (1997, p. 167).
NOTES
287
p. 221
Albert Eschenmoser: Eschenmoser’s first studies
(Eschenmoser 1991, 1993, 1994, 1999; Bolli et al. 1997) focused on 6-carbon
(or hexose) sugars, which assemble into polymers called pyranosyls (he
called these alternative nucleic acids p-RNAs). In 2000, his group reported
the surprising synthesis of TNA nucleic acid with the 4-carbon sugar threose
(Schöning et al. 2000). Leslie Orgel (2000, p. 1307) writes: “The existence of
a molecule that is significantly ‘simpler’ than RNA, that resembles RNA more
closely than do peptide nucleic acids . . . is encouraging to those who believe
that RNA was preceded by one or more simpler genetic materials.” For use-
ful overviews, see Eschenmoser (1999, 2004).
Regarding this work, Jack Szostak writes: “Eschenmoser [is] one of the
world’s pre-eminent organic chemists, who should have shared the Nobel
Prize with Woodward for conformational analysis and B12 synthesis—who
in his retirement has taken on the task of synthesizing systematically all the
reasonable alternatives to RNA in order to answer the question of why na-
ture chose the nucleic acids that are used today in all cellular life.” [Jack
Szostak to RMH, 21 August 2004]
p. 222
“peptide nucleic acid”: The concept of PNAs was introduced
by Nielsen et al. (1991), Egholm et al. (1992), and Nielsen (1993), and elabo-
rated on by many other researchers (Wittung et al. 1994, Diederichsen 1996,
Diederichsen and Schmitt 1998, Nielsen 1999, and Orgel 2003). Stanley
Miller (1997, p. 169) comments, “PNA has demonstrated that nucleic acids
with backbones other than sugar phosphates need to be considered.”
The original PNA used a nonbiological amino acid called aminoethyl
glycine—a nonchiral molecule. Subsequent studies found that PNA cannot
form a DNA-like double strand if the peptide backbone is constructed from
homochiral biological amino acids (known as α amino acids). Rather, the
backbone must consist either of so-called β amino acids or of strictly alter-
nating D and L α amino acids (Diederichsen 1996, Diederichsen and Schmitt
1998, and Orgel 2003).
p. 222
plausible genetic molecules: Steven Benner takes the chemical
range of RNA-like molecules even further as he imagines the possibilities of
alternate biochemistries (Switzer et al. 1989, Piccirilli et al. 1990, Bain et al.
1992, and Hutter and Benner 2003). He has developed an Artificially Ex-
panded Genetic Information System (AEGIS) with eight new base pairs and
a variety of new genetic polymers, some of which might be stable in non-
aqueous liquids, such as ammonia, and thus serve as models for alien bio-
chemistries (Benner and Hutter 2002). Miller and co-workers also explored
the possibility of alternative bases (Kolb et al. 1994).
p. 222
The PAH World: [This section is based in part on extensive
notes provided by Simon Nicholas Platts to RMH, 10 August 2004]
p. 223
Max Bernstein: Bernstein’s seminar on November 19, 2001,
288
GENESIS
was entitled “Interstellar Inception of Meteoritic Organics and Implications
for the Origin of Life.” The seminar is archived at www.origins.rpi.edu. The
talk on ultraviolet irradiation of PAHs was based on research described in
Bernstein et al. (1999b). Becker et al. (1997) present analytical evidence for
PAHs delivered from space.
p. 223
September 2003 conference: The Seventh Trieste Conference
on Chemical Evolution and the Origin of Life was held at the International
Centre for Theoretical Physics, Trieste, Italy.
p. 224
“On the return flight”: Nick Platts’ airline ticket is dated Sep-
tember 30, 2003.
p. 224
PAHs would have been abundant: Desiraju and Gavezzotti
(1989) present a useful review of PAH structures. An unfortunate confusion
in nomenclature arises, because many chemists refer to PAHs as “polynuclear
aromatics,” or PNAs—the same abbreviation origin-of-life workers use for
peptide nucleic acids.
p. 224
“functionalized”: Bernstein et al. (1999b, 2003)
p. 229
discotic organization: Discotic self-organization was first de-
scribed by Chandrasekhar et al. (1977). For reviews, see Chandrasekhar
(1993), Kumar (2002, 2003), Chandrasekhar and Balagurusamy (2002), and
Friedlein et al. (2003).
p. 230
“I think it’s worth pursuing . . .”: [Jack Szostak to RMH, 3 June
2004]
p. 230
“An experimental demonstration . . .”: [Leslie Orgel to RMH,
4 June 2004]
p. 230
“I thought it was interesting . . .”: [Gerald Joyce to RMH, 7
June 2004]
p. 230
“For now it is fascinating . . .”: [Andrew H. Knoll to RMH, 7
June 2004]
p. 230
“Thank you for submitting . . .”: [Editors of Nature to Sim
on
Nicholas Platts, 10 June 2004]. We later learned that, owing to an unusual
glut of submissions, they never considered the scientific merits of the piece.
p. 231
HBC for a thousand dollars: The Norwegian chemical com-
pany Chiron AS offers 10 milligrams of hexabenzocoronene for $1,078 in-
cluding shipping. Other possible gratis sources included Prof. Klaus Muellen
at the Max Planck Institute for Polymer Research in Mainz, Germany, and
Prof. Shigeru Ohshima and Dr. Minoru Takekawa at Toho University in
Chiba, Japan.
p. 231
informal talk: The Carnegie talk was part of an irregular series
by the Geobiology Discussion Group. The NASA video seminar was part of
the Forum for Astrobiology Research.
p. 231
thesis defense: The thesis incorporated a range of projects re-
NOTES
289
lated to origins chemistry, though the PAH World idea formed the center-
piece.
p. 232
Dave had also published: Deamer (1997, p. 249). Deamer en-
visioned individual functionalized PAHs incorporated sideways into mem-
branes, where they could absorb near-ultraviolet and blue wavelengths and
effectively act as photoelectric power sources.
18
THE EMERGENCE OF COMPETITION
p. 233
“It is evident . . .”: Sagan (1961, p. 177).
p. 233
Origin of Species: Darwin (1859).
p. 233
continue unabated: Scientists who trivialize these public con-
cerns regarding the validity of scientific accounts of life’s origin and evolu-
tion do so at their peril. The theory of evolution, by which random molecular
changes led through a chance process to the human species, can be seen as
raising perplexing philosophical questions about the origin and meaning of
human existence (see, e.g., National Academy of Sciences 1998, Gould 1999,
K. R. Miller 1999, Fry 2000, Ruse 2000, Pennock 2002, Witham 2002, and
Forrest and Gross 2004).
p. 235
Competition among self-replicating cycles: See, for example,
Ycas (1955) and de Duve (2005).
p. 236
Here’s what Spiegelman: Mills et al. (1967). Note that the rapid
evolution of this system involved a cycling imposed by the experimenters.
Recall that cycling is one of four factors that may promote emergent behav-
iors (see Chapter 1).
p. 237
“Our ultimate goal . . .”: Zimmer (2004, p. 37).