H00102--00A, Front mat Genesis
Page 20
MODULAR LIVING
Perhaps the most distinctive characteristic of the molecules of living
organisms is their modular design. This familiar strategy is similar to
that of modern architects, who rely for the most part on standard
building materials. They use mass-produced bricks, beams, windows,
doors, stairs, lighting fixtures, and so on to assemble an almost infinite
variety of commercial and private buildings.
You don’t have to build in that way. A multimillionaire acquain-
tance recently created the most extraordinary mansion, with every
square foot of walls and floor, every light and bath fixture, every door
and window custom-designed and hand-crafted. It’s an amazing house,
with secret passages, unexpected nooks, and hidden closets, all lov-
ingly constructed of the finest woods, stone, and other extravagant
materials. Such personalized craftsmanship is wonderful to see, but
inordinately expensive. Most of us choose a more economical path. By
relying on a few standard construction modules, buildings are faster
and cheaper to design and build. But modularity doesn’t imply unifor-
mity. You can design a unique dwelling of almost any size or shape
from simple components available through any hardware or building
supply store.
The same modular principle holds for life’s carbon-based molecu-
lar building blocks. Four key types of molecules—sugars, amino acids,
nucleic acids, and hydrocarbons—exemplify life’s chemical parsimony.
THE MACROMOLECULES OF LIFE
135
Sugars are the basic building blocks of carbohydrates, Earth’s most
abundant biomolecules. Many common sugars in our diets, including
the fructose of honey, the sucrose of cane sugar, and the glucose of
fruits, are small molecules consisting of at most a few dozen atoms.
These energy-rich molecules incorporate carbon, oxygen, and hydro-
gen typically in about a 1:1:2 ratio. But most of life’s sugar molecules
are locked into macromolecules—countless individual sugar molecules
linked together to form giant polymers, such as the fibrous cellulose of
plant stems or the bulky starch of potatoes.
Amino acids are small molecules that link together to form pro-
teins. Proteins serve as the chemical workhorses of life, with myriad
vital functions: They form tissues and strengthen bone; they act as hor-
mones to control glandular functions; they clot blood, digest food, and
promote the thousands of chemical operations essential to life. All pro-
teins form from long chains of hundreds to thousands of individual
amino acid molecules, lined up like beads on a string. These chains
fold into the most wonderful shapes, each protein folded in such a way
as to accomplish a specific chemical task.
The vital genetic molecules DNA and RNA are also lengthy
chainlike polymers, assembled from small molecules called nucle-
otides. Each nucleotide, in turn, is constructed from three small mo-
lecular parts: a 5-carbon sugar (ribose in RNA, its cousin deoxyribose
in DNA); a base (one of five closely related ring-shaped molecules);
and a phosphate group (a tiny cluster made up of a phosphorus atom
surrounded by four oxygen atoms). RNA consists of a long chain of
single nucleotides, while in DNA two such chains link together and
twist into the famed “double helix” structure.
Finally (as we’ll see in the next chapter), arrays of elongated hy-
drocarbon molecules called lipids, including a wide variety of fats and
oils, coalesce in every cell to form membranes, store energy, and per-
form other critical functions.
The most enticing aspect of Stanley Miller’s experiment and the
discoveries of subsequent prebiotic researchers was that they synthe-
sized components (or at least close relatives) of all four groups—car-
bohydrates, proteins, nucleic acids, and lipid membranes. No wonder
so many researchers were optimistic that an understanding of life’s
emergence was at hand.
But this molecular catalog of success ignores a puzzling part of the
prebiotic synthesis story. For every useful molecule produced, many
136
GENESIS
other species with no obvious biological function complicate the pic-
ture. Take sugar molecules, for example. All living cells rely on two
kinds of 5-carbon sugar molecules: ribose and deoxyribose. Sure
enough, several plausible prebiotic synthesis pathways yield small
amounts of these essential sugars. But for every one of these molecules
produced, many other 5-carbon sugar species also appear—xylose, ara-
binose, and lyxose, for example. Adding to this chemical complexity is
a bewildering array of more than 100 3-, 4-, 6-, and 7-carbon sugars, in
chain, branching, and ring structures—of which life uses only a small
handful.
As if that weren’t enough of a problem, life is even choosier about
its molecules. Many organic molecules, including ribose and deoxyri-
bose, come in mirror-image pairs. These left- and right-handed varie-
ties are in most respects chemically identical. They possess the same
chemical formula and many of the same physical properties—identi-
cal melting and boiling points, for example. But they differ in their
shapes, just like your left and right hands. Laboratory synthesis usually
yields equal amounts of left- and right-handed sugars, but finicky life
employs only the right-handed sugars, never the left.
Given the disparity between the rich variety of prebiotic molecules
and the apparent paucity of biomolecules, is it possible that we’re fool-
ing ourselves? Might the earliest life-forms have used a more diverse
suite of organic molecules and a different repertoire of biochemical
pathways? It turns out that living cells hold clues that are now being
teased out by the remarkable field of molecular phylogeny.
MOLECULAR PHYLOGENY AND
THE “LAST COMMON ANCESTOR”
The complete chemical arsenal of each living species is recorded in its
unique genome, an encoded sequence of millions to billions of DNA
“letters,” the base pairs that form the rungs of DNA’s double helical
ladder. The four-letter DNA alphabet—A, G, T, and C (for the purines
adenine and guanine and the pyrimidines thymine and cytosine)—is
sufficient to spell out all the genetic information of any organism.
What’s more, all cells share the same mechanism for converting ge-
netic instructions into the proteins that serve in many chemical and
structural roles. That’s why genetic engineers can use a simple bacte-
THE MACROMOLECULES OF LIFE
137
rium, such as E. coli, to synthesize human growth hormone, or insulin,
or other valuable pharmaceuticals.
A central assumption of molecular phylogeny is that the genomes
we see today evolved over billions of years from earlier ancestral cells,
via the gradual mutation of DNA sequences. Comparative examina-
tion of many genomes reveals marked similarities, as well as important
differences that have inexorably arisen by this slow evolutionary pro-
> cess. Differences among DNA sequences suggest the evolutionary
branching; the more dissimilar the sequences of two species, the longer
ago they are likely to have split from a common ancestor. DNA se-
quences that show little variation among many diverse species (so-
called highly conserved sequences) are more likely to represent ancient,
essential biochemical traits.
The power and promise of phylogenetic analysis is epitomized in a
remarkable recent study of early English literature. University of Cam-
bridge biochemists Adrian Barbrook and Christopher Howe teamed
with British literary scholars to analyze 58 different fifteenth-century
manuscript copies of the Wife of Bath’s Prologue from Geoffrey
Chaucer’s The Canterbury Tales. No copy of the late fourteenth-
century original in Chaucer’s hand is known, and significant varia-
tions among the many early hand-copied sources raise doubts regard-
ing the author’s original text.
For their Chaucer analysis, Barbrook, Howe, and co-workers em-
ployed the same computer techniques used by evolutionary biologists
to identify the most primitive organisms. They entered each of the
Prologue’s 850 lines from all 58 versions into the computer and
searched for textual similarities and differences. Features common to
most sources presumably reflected the original text, while variations
that arose from copying errors or deliberate changes were used to con-
struct a kind of genealogy of the manuscripts.
The British team found that 44 manuscripts fell neatly into 5
groups, evidently descended from 5 different copying sources. (The
remaining 14 showed more extreme deviations and were eliminated
from consideration.) One group of 11 manuscripts proved crucial, for
it lay much closer to the presumed original than the others. Surpris-
ingly, these 11 texts had received comparatively little study from liter-
ary scholars. “In time, this may lead editors to produce a radically
different text of The Canterbury Tales, ” Barbrook and colleagues
concluded.
138
GENESIS
Ld2
F Ry2
O
Tc1
Ln
Bw
A
Ra3
En1
Cn
Ma
li
Ch
Tc2
Ad1
Dd
Ds
Cx1
En3
B
Ne
O
Ph2
Ht
He
Bo1
E
Gg
Hg
Ad3
Sl
O Ha5
N
S12
La
Bo2
Pw
DI
Cp
Ld1
Ph3
To
Lc
Ry1 SI1
Mg
C/D
Fi
Computer-aided analysis of several dozen hand-copied manuscripts of Geoffrey
Chaucer’s Canterbury Tales points to several distinct groups of texts, denoted by letters. Each manuscript is represented as a line on this diagram; the length of the lines corresponds to the amount of deviation from a presumed primary source. Of these,
the groups marked “O” appear to be closest to Chaucer’s lost original (after Barbrook et al., 1998).
Molecular phylogenists adopt the same analytical approach. Their
“texts” consist of strands of genetic molecules—DNA or its close
cousin, RNA—with long sequences of the genetic letters. Thanks to
new, rapid sequencing techniques, numerous genomes have been
documented, including more than a hundred genomes of various mi-
crobes. Phylogenists use powerful computer algorithms to compare
their genetic texts.
The universally acknowledged pioneer of molecular phylogeny is
University of Illinois geneticist Carl Woese, a shy and retiring maverick
who had to wait many years for widespread scientific acceptance of his
ideas. In a landmark 1977 article in the Proceedings of the National
Academy of Sciences, “Phylogenetic structure of the prokaryotic do-
main: The primary kingdoms,” Woese and Illinois colleague George
Fox uprooted what had become the firmly established tree of life. Prior
THE MACROMOLECULES OF LIFE
139
to the “Woesian revolution,” most biologists recognized five kingdoms
of living organisms: animals, plants, fungi, protoctists (complex single-
celled organisms with a membrane-bounded nucleus), and bacteria
(metabolically diverse organisms that lack a nucleus). Based on his
laborious phylogenetic analyses (which were much more difficult in
the 1970s than they are today), Woese realized that animals, plants,
fungi, and eukaryotes are remarkably similar in their biochemical char-
acteristics and so constitute just one domain of life, the Eukarya.
Prokaryotes, on the other hand, displayed astonishing chemical diver-
sity and fell into two distinct kingdoms, which he called Bacteria and
Archaea. Bacteria were well known for their role in causing disease, but
the Archaea, that as prokaryotes resemble other bacteria in many ways,
constituted an unrecognized group of microbes. So contentious was
this view of life that it took almost two decades to gain general acceptance.
In retrospect, the lateness of Woese’s discovery should not seem
too surprising. Most species in the two microbial kingdoms, Bacteria
and Archaea, occur as nondescript microscopic spheres or rods that
are virtually impossible to distinguish, even with sophisticated chemi-
cal and physiological tests. Consequently, previous workers lumped
them all together. Only after the application of molecular phylogeny
did the profound differences become obvious.
Woese’s initial intention was to unravel aspects of evolution—to
establish a top-down family tree of life and infer the complex history
of branchings from parent to daughter species. This evolutionary pur-
suit led quickly to insights regarding the nature of the last common
ancestor. He proposed, for example, that Archaea and Bacteria arose
long before Eukarya.
Other discoveries followed. Many of the most primitive microbes
are extremophiles that thrive at elevated temperature. To many re-
searchers, Woese’s discoveries thus lent credence to the idea of a deep,
hot emergence of life. Other scientists, however, quickly took issue with
that conclusion. Deep microbes might well have been the only survi-
vors following a massive asteroid impact and thus, by default, became
the last common ancestors of life on Earth today. But those heat-lov-
ing microbes might well have evolved from strains of earlier, surface-
dwelling cells.
Recent studies point to other intriguing possible characteristics of
the presumed last common ancestor. For example, many of the most
primitive Archaea are autotrophs, organisms that synthesize their own
140
GENESIS
Bacteria
ium
Escher
vobacter
ichia
Fla
us
Chlam
ydia
Methanother
Archaeoglob
illum
Methanococcus
Methanospir
mus
Bacillus
us
Ther
Archaea
m
moproteus
Ther
ex
Aquif
Homo
Giardia
ramecium
Pa
ostelium
Dicty
Euglena
Eukarya
Carl Woese compared the genetic sequence of many different organisms, especially
microbes, to construct a phylogenetic tree of life. He found three distinct branches of life, including the previously unrecognized Archaea. The majority of the most deeply rooted organisms are extremophiles living at high temperature (after Pace, 1997).
THE MACROMOLECULES OF LIFE
141
biomolecules. However, many origin specialists, Stanley Miller and his
colleagues among them, have long argued that the first cells must have
been heterotrophs, which scavenge molecules from their environment.
Once again, the controversy cannot be resolved by phylogenetic stud-
ies, for deep-dwelling autotrophs that evolved from surface hetero-
trophs might have been the sole survivors of a globe-sterilizing event.
Additional complexity arises from the tendency of microbes to
swap sections of DNA. Remarkably, throughout the history of life, cells
have picked up chunks of DNA from completely different species to
form new, hybrid genomes. Thus the idealized view of an unbroken
branching history of DNA evolution from parent to daughter is in-
valid. There is no single “last common ancestor.”
In spite of these uncertainties, molecular phylogeny provides in-
valuable information regarding the shared biochemical heritage of all
cells—information that continues to inform origins research. Two ob-
servations stand out. First, all cells employ RNA to carry genetic infor-
mation and assemble proteins. The earliest genetic mechanism thus
points to an ancient “RNA World” (see Chapter 16). Second, at the
heart of every cell’s chemical machinery lies a simple metabolic strat-
egy called the citric acid cycle, which is powered by simple chemical
reactions. Any successful model of life’s emergence must thus account
for the origin of this cycle (see Chapter 15).
An important conclusion from these phylogenetic studies is that
Earth’s earliest cells were not so different from those of today. They
probably relied on similar, though simpler, biochemical pathways.