Origins of Life and the RNA World:
Never Underestimate the Power of Soup
How life began on earth is one of those Big Questions whose answers rely
on understanding the tiniest ones. The folks who work on it - molecular evolutionary biologists
- study the smallest units of life: DNA,
RNA, and ribosomes.
Huddled in their labs, seemingly removed from everyday human experience,
they try to find out what's ultimately responsible for it.
To figure out what happened millions of years ago, scientists first study
how life works now and backtrack. Today's cells keep DNA, their all-inclusive
instruction manual, under tight wraps in the nucleus.
Tiny pores in the wrapping are the only way in or out. If the cell had a
library, DNA would be a complete set of encyclopedias; it has two long strands
of deoxyribonucleic acid and is much too big to fit through the pores.
When
the cell needs directions, the DNA makes a copy of the particular pages
required in the form of messenger RNA,
a short, single strand of ribonucleic acid that can leave the nucleus.
Outside the nucleus lies the cytoplasm, the cell's framework. Messenger
RNA (mRNA) wends its way through the maze looking for the nearest relay
station: a ribosome. Ribosomes get the word, but before they can act on
it, they have to put it into words they can understand: they don't speak
mRNA. Instead, they call in their interpreters: transfer
RNA (tRNA). These go-betweens recognize parts of the mRNA message and
give it to the ribosome.
DNA's instructions tell the ribosomes to make proteins, which carry out
functions in the cell and in the body ranging from digesting the sandwich
you had for lunch to determining your eye color. Ribosomes assemble proteins
from building blocks, called amino acids, that tRNAs line up in the right
order. Yet another kind of RNA in the ribosome (rRNA) helps move the assembly
line along.
Researchers working out their understanding of this machinery wondered:
which came first, DNA, RNA or protein? The first information molecule must
have been able to reproduce itself and carry out tasks similar to those
done by proteins today, which limited the choice. Proteins were obviously
important, since so many cellular functions depended on them; but proteins
are even bigger and more complicated than DNA and can't make copies of themselves
without DNA and RNA. The chemicals making up DNA include parts of RNA, so
DNA was out. That left RNA.
Scientists imagined an "RNA World", in which primitive RNA molecules
assembled themselves randomly from building blocks in the primordial ooze
and
accomplished some very simple chemical chores. But as far as anyone knew,
RNA couldn't do anything but carry information from DNA to ribosomes.
That changed in the early 1980's, when two biochemists, Sidney
Altman and Thomas
Cech, discovered independently a kind of RNA that could edit out unnecessary
parts of the message it carried before delivering it to the ribosome. Since
RNA - ribonucleic acid - was acting like a type of protein known as an enzyme,
Cech called his discovery a ribozyme. The two were awarded the Nobel Prize
for Biochemistry in 1989.
Ribozymes rocked the molecular biological world. There was much rejoicing
among true believers in the RNA World, but the skeptics scoffed. An RNA's
being able to cleave itself was all well and good, they argued, but what
about all the other chemical reactions that RNA would have to perform as
the sole information molecule and enzyme? They demanded more proof, in the
form of other RNA-driven reactions.
But they weren't terribly receptive when they got it. A decade before Altman
and Cech's experiments, biochemist Harry
Noller had found more than he bargained for when he set out to map ribosomes
and figure out which of its proteins were responsible for translation of
mRNA. First, he treated the ribosomes with protein-digesting enzymes to
show that the rest of the ribosome couldn't translate mRNA.
"We attacked them with everything we could think of, and the things
still worked," he says. Eventually, he and his colleagues at the University
of California, Santa Cruz had to accept that it was the RNA that was doing
the translating. They published a paper to that effect in 1972, and were
ignored completely. It seemed nobody wanted to know that the established
model of how things worked in cells was wrong.
"When you talk about the evolution of ribosomes, you're really talking
about the evolution of the genetic code, of protein synthesis, and life
itself," Noller says; and it's not overstating the case. After 20 years
of work, Noller's team has identified a few of the crucial places in ribosomal
RNA that allow translation; and spirits are as high as a good lab scientist
ever lets them get.
Two floors down, on the other side of Sinsheimer Laboratories, Charles
Wilson has watched the evolution of "smart" ribozymes up close.
He's reached one of the great milestones in gaining support for the RNA
World: getting RNA to speed a reaction that doesn't involve DNA or RNA at
all.
Putting carbon and nitrogen atoms together - alkylation - is essential to
virtually all cellular function, and it happens countless times a minute
in living
tissue. Wilson found and cultivated ribozymes that could carry out alkylation
a hundred times faster than the protein that's normally responsible for
it in a series of experiments designed to mimic evolution.
He began with billions of messenger RNAs, random sheets torn from volumes
of DNA , and presented them with carbon and nitrogen atoms. While the vast
majority of messengers scratched their heads in bewilderment, a few were
able to stick one of each atom together. The reward for these clever RNAs
was the chance to make babies.
Well, not exactly. RNAs can't reproduce like animals or plants, but given
the right materials, they can make copies of themselves that are more or
less identical. Surprisingly, it's the less-identical ones - those that
have errors in them - that win over time. Subtle differences that may make
an RNA better able to put carbon and nitrogen together - or render it completely
useless, which is usually what happens. By selecting the RNAs that could
speed alkylation and then letting them reproduce, generation after generation,
Wilson eventually wound up with a group of RNAs that were really good at
sticking the atoms together.
Natural evolution takes much longer, centuries and millennia rather than
weeks and months. But the process is the same, and Wilson's experiments
provide the kind of support that RNA World detractors asked for. He's also
trying to find RNAs that control other reactions and change them - like
turning cancer genes off or growth hormone production on.
Short of a time machine or records from alien observers, says Wilson, we'll
never know exactly how life on earth began. Or will we? Noller isn't so
sure. "Twenty years ago, if you went around saying that RNA could perform
chemical reactions, they'd throw a net over your head; but today nobody
disputes it," he says. "Who's to say what will happen?"