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How Sex May Have Started it All

STRANDED SEX:© 2003 Elsevier ScienceIn this two-pot recombination scheme a ribozyme is incubated with an excess of RNA substrate A-B. The 3' portion of the substrate is covalently attached to the 3' end of the ribozyme in a "pick-up-the-tail" (PUTT) reaction. When the ribozyme is purified and incubated with an excess of substrate C-D, recombination (REC) of the substrates results in the product C-B. Exogenous GTP marginally improves recombination frequency which ranges from 5% to 45%. (From

Jack Lucentini
<p>STRANDED SEX:</p>

© 2003 Elsevier Science

In this two-pot recombination scheme a ribozyme is incubated with an excess of RNA substrate A-B. The 3' portion of the substrate is covalently attached to the 3' end of the ribozyme in a "pick-up-the-tail" (PUTT) reaction. When the ribozyme is purified and incubated with an excess of substrate C-D, recombination (REC) of the substrates results in the product C-B. Exogenous GTP marginally improves recombination frequency which ranges from 5% to 45%. (From Chem Biol, 10:1233–43, 2003)

Some researchers delving into the origins of life have sex on the brain. The prevailing thought in the field says that sex, typically defined as reproduction involving the fusion of genomes, emerged no more than 1.2 billion years ago. This is when eukaryotes, often haughtily considered the only organisms privileged enough to partake, evolved. But some are broadening the definition of the natural act and implicating it...

ROILING IN RECOMBINATION

Supporters stand by their findings. Recombination "may have played a role in the origins of life," says Niles Lehman, associate professor of chemistry at Portland State University in Oregon. He cites as evidence a finding from his laboratory that RNA molecules, possibly similar to precursors of modern genes, can catalyze recombination.1 He also points out new research that suggests bacteria can fully merge their genomes in a process that has striking similarities to some aspects of sexual reproduction.2

Some researchers doubt, however, that these findings are significant for explaining how sex evolved or contributed to life's origins. Lehman's arguments "are based on poorly defined, poorly distinguished processes," says Rosemary J. Redfield, associate professor of zoology at the University of British Columbia, Vancouver. True sex, which has been defined as syngamy (gamete fusion), nuclear fusion, and meiosis,3 is commonly regarded as unique to eukaryotes. Simpler organisms, mainly bacteria, conduct "parasexual" or sex-like activities involving limited exchange or uptake of genes, but these processes are largely distinct from reproduction. Nevertheless, they do include many of the same mechanisms of recombination, or DNA exchange, found in sex.

SEX IN VITRO

The standard view took on a new dimension in 1998 when Carl Woese at the University of Illinois, Urbana-Champaign, concluded that gene exchange among the earliest cells was so rampant that the concept of a single first organism is meaningless. "The universal ancestor is not a discrete entity. It is, rather, a diverse community of cells," he wrote. 4

Lehman says this concept should be taken further, to not only the first cells but also to their forebears, such as the naked, self-replicating RNA molecules that some researchers believe preceded them. These molecules had to be complex enough to catalyze their own replication, but they couldn't become complex without first undergoing repeated cycles of replication and selection, a chicken-and-egg conundrum that remains an outstanding biological riddle.

Recombination could help solve it, Lehman argues.5 Depending on the position of recombination points, sequence swapping can lengthen one molecule and shorten another. Lehman says repeated cycles of this process could build complex molecules far more quickly and efficiently than polymerization, the process usually presumed to have created them. Polymer-ization would involve adding nucleotides to the molecules one by one. For struggling proto-organisms, this might be like trying to create a coherent novel by adding one random letter at a time.

By contrast, recombination would add bits of sentences and paragraphs; while still unlikely to create meaningful literature, it would be more promising. In an in vitro evolution experiment, Lehman subjected RNA molecules to repeated rounds of mutation and replication while applying selective pressure for desired properties. The process revealed RNAs that catalyze recombination between two other RNAs. Recombination can be easy and efficient, and it is chemically nearly spontaneous, unlike polymerization, Lehman says. Further bolstering his case, he claims, are findings that recombination enzymes may be among the genome's most primitive.3

The findings are intriguing in the context of an RNA-world hypothesis, says Andres Jäschke, professor of pharmaceutical chemistry at the University of Heidelberg. But, "I think it's impossible to directly prove that RNA has actually done this in history," he notes. Such findings could, however, aid researchers in developing useful catalysts and ligands through in vitro evolution.6 For instance, a researcher could develop three separate RNAs with useful functions, then test different ways to recombine their functional domains into a single molecule. "It gives you more freedom to incorporate new functions," says Jäschke.

VIRTUAL SEQUENCING SWAPPING

<p>SLIMY SEX:</p>

Courtesy of Daniel L. Gustafson

The minuscule New Zealand mud snail Potamopyrgus antipodarum has been cited in favor of a theory that parasites encourage the evolutionary persistence of sex. In this view, sex lets organisms shuffle their genes quickly enough to compete in an evolutionary arms race with a parasite. In P. antipodarum, which can switch between sexual and asexual lifestyles, researchers have correlated sexuality with the incidence of parasitic flatworm infections (Nature, 328:519–21, 1987). Recently, researchers have identified other possible ways that parasites might be related to sex – some suggest parasitic genetic sequences might have started it all.

Researchers in Hungary have conducted computer simulations testing Lehman's hypothesis that recombination helped develop early genomes. The result: "Yes, recombination helps, but only a little bit," says Mauro Santos, a fellow at Collegium Budapest. Submitted research, he says, shows that recombination would allow genomes to grow 25% faster than they would without recombination.

Other findings make ancient sex look more likely, some researchers say. Jean-Pierre Gratia, a faculty member at the Pasteur Institute of Brussels, has reported that, in breach of all textbook dogma, bacteria can have sex.2 Certain Escherichia coli cells can merge, creating a temporary combination of two genomes allowing recombination between them, he writes. Gratia has "shown quite a lot of evidence" to demonstrate the phenomenon, says Bharat Patel, an associate professor of biomolecular and biomedical sciences at Griffith University, Brisbane, Australia. Proof that it's a common or historical phenomenon is far off, though. "It would be interesting to see if there's any evidence of it in the fossil record," Griffith says. The result could further support the antiquity of recombination, suggests Lehman.

Thomas Cavalier-Smith, professor of evolutionary biology at the University of Oxford, is unconvinced. He cites several shortcomings in Gratia's paper, including vague electron microscopy results and no definition of sex. "It's a pity, because they may have an interesting phenomenon," he says. Even so, Cavalier-Smith adds, the process cannot be evolutionarily related to eukaryotic sex. Among other reasons, bacteria don't undergo meiosis, and they lack nuclei, which are necessary for the nuclear fusion that accompanies the union of gametes.

Regardless of whether pre-eukaryotes might have had sex, Santos and colleagues have conducted computer simulations to analyze how such a process could have influenced evolution. They simulated "protocells," comprising a few replicating molecules within a closed membrane programmed to divide into two smaller cells each time they double in size. The researchers examined how the entities "evolve" with and without occasional random cell fusion programmed into the system.7

Paradoxically, their findings show that sex hurts the proto-organisms in their earliest evolution, because it allows parasitic or "selfish" genes to spread. But once a parasite has spread, sex is the only way the population can fight it. One theory holds that sex lets creatures shuffle their genes quickly enough to out-evolve parasites. Santos speculates sex could have begun as "a means for parasites to spread all over the population," and sex-inducing parasites might even have started the process. Gratia's work echoes this. In his E. coli experiments, he writes, the bacteria may get their fusion abilities from a virus.

TAKING THE RIGHT PRECAUTIONS

None of the new hypotheses has yet found a secure place in accepted theories of how sex evolved. Many question whether recombination can be considered sex to any extent. If not, theories of how recombination evolved may be irrelevant to how sex evolved.

Moreover, some researchers in the past few years have presented influential arguments that recombination has no important function among primitive organisms, at least for life forms familiar to biology. Redfield argues that the major recombination enzymes also conduct DNA replication and repair, so recombination is probably a side effect of these more vital activities.8 She also attests that genes mediating gene transfer among prokaryotes are selfish genes that did not evolve to benefit their recipients, but to promote their own proliferation.

Recombination's unclear or nonexistent functions, as well as a frequent tendency to conflate it with sex, leads to off-base theorizing about these phenomena as useful adaptations, Redfield says. Lehman argues, however, that even if extant organisms don't need recombination, prebiotic ones might have. Santos raises a semantic argument cautioning against definitions of sex that exclude anything but the type we engage in. "People think sex and reproduction are same thing, but they are not," he insists.

Ultimately, just as health officials today advise those who would engage in sex to take precautions, similar advice may serve those who would research sex-related subjects. Says Red-field: "There's a whole lot of painful intellectual hygiene that's needed if you're going to deal with these ideas."

Jack Lucentini jekluc@aol.com is a freelance writer in New York City.

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