By David N. Leff

Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.

What¿s the use of having sex? Many forms of life reproduce just fine without lugging around the baggage of male-female copulation.

In asexual reproduction there is no genetic recombination, so a beneficial mutation ¿ such as drives evolution ¿ is stuck with the genetic environment in which it first shows up. What if that environment is also loaded with deleterious mutations? Those bad guys can hold back the spread ¿ the evolution ¿ of that upstart good-guy gene. Individual clones containing various beneficial mutations compete with one another, which slows adaptation. But sexual mating gives the beneficial mutation the benefit of genetic recombination, which presents it with an entirely new genetic setting each generation.

A research report in Science dated Oct. 19, 2001, titled ¿Sexual recombination and the power of natural selection,¿ confirms this comforting rationale. Its authors are in the department of ecology, evolution and marine biology at the University of California at Santa Barbara.

For well over a century, biologists have been taught that sex produces variation, which promotes evolutionary adaptation. The Science paper puts this doctrine to the test. It deals with several downsides to sex: For one thing, sexual reproduction exacts a 50 percent reduction in output of progeny. If a female can produce viable offspring on her own, the challengers ask, why dilute her genetic contribution to subsequent generations by mating with a male?

Another postulated advantage of sex lies in eliminating deleterious mutations rather than combining beneficial ones. As a commentary to the article points out, ¿Empirical tests of these hypotheses have failed to predict a clear winner. This leaves the area of sex ripe for good, clear experiments.¿

Which is what the Santa Barbara authors undertook. They converted the fruit fly Drosophila melanogaster, which enjoys a normally sexual lifestyle, into a clonal organism. They accomplished this sex change by constructing female flies with synthetic chromosomes containing almost the strain¿s entire genome. They used these females to propagate ¿asexual males¿ that mated each generation but could not recombine genes with their mates. They predicted that a higher proportion of beneficial mutations would succeed in a normal sexual population than in their artificial asexual one.

The researchers report 34 separate experiments ¿ 17 with and 17 without recombination ¿ to average the experimental outcome. Their paper concludes: ¿The substantial costs associated with sexual recombination are well established, making its prevalence in nature an evolutionary enigma. Our results experimentally verify a counteracting advantage of recombining compared to clonal lineages: reduced accumulation of harmful mutations and increased accumulation of beneficial mutations. The magnitude of this benefit will accrue over geological time and promote the superior performance of recombining lineages at both the level of species within communities (clonal vs. sexual species) and genes within chromosomes (non-recombining Y-linked versus recombining X-linked genes).

¿Notwithstanding,¿ the commentary concluded, ¿evolutionary geneticists will continue to be very interested in sex.¿

Structural Analysis Highlights Cancer-Prone Region In Mutated Breast Cancer Gene

As known since 1994, a risk factor for familial and early onset breast cancer is mutation in the tumor-suppressor protein BRCA1. The intact protein earns a living by repairing damaged DNA, transcribing RNA and checking up on cell-division checkpoints, as well as suppressing mammary tumors.

The mutations in its 1,863-amino-acid genome tend to bunch at the N-terminal region of BRCA1, called the RING domain, in complex with an associated protein called BARD1. This location suggests that the cancer-predisposing mutations within these structures may compromise the healthy protein¿s tumor-suppressing activities.

¿It¿s still unclear,¿ notes a commentary in the October issue of nature structural biology, ¿why inherited mutations in the BRCA1 gene predispose women to breast and ovarian cancers.¿ To address this deficiency, the journal carries an article titled: ¿Structure of a BRCA1-BARD1 heterodimeric RING-RING complex.¿ Its authors are at the University of Washington at Seattle. Their paper concludes that the structure they obtained ¿provides a framework for understanding cancer-causing mutations at the molecular level.¿

Three Mutant Protein Clumps Probed In Lewy Bodies ¿ Parkinson¿s Disease Hallmark

Parkinson¿s disease (PD) comes in at least three persuasions ¿ two inherited, one non-inherited. Mutations in one of two different proteins, parkin or alpha-synuclein (aS), mark the inherited versions, but how they lead to the same disorder is baffling. One answer: Both proteins interact with a third, synphilin, and the mutations disturb this interaction. Parkin was already known to mark certain proteins for destruction by recruiting a fourth ¿ scavenger ¿ protein called ubiquitin.

A paper in the October issue of Nature Medicine carries clues to the puzzle. It¿s title: ¿Parkin ubiquinates the a- synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson¿s disease.¿ Its authors are neuroscientists at the Johns Hopkins University School of Medicine in Baltimore.

Many of the dead or dying dopamine-producing neurons in PD contain protein blobs called Lewy bodies ¿ a PD hallmark. They include parkin, aS and synphilin. ¿Understanding the formation of these clumps,¿ observes the senior author of the paper, neuroscientist Ted Dawson, ¿might eventually help identify targets for new treatments.¿ He added: ¿We are trying to see if the genetic mutations converge with what¿s known about the non-inherited disease, as is the case for Alzheimer¿s disease.¿

¿The major findings of this report,¿ the paper states, ¿are that parkin interacts with and ubiquinates the aS interacting protein, synphilin-1, and ubiquinates the Lewy-body-like inclusions that are formed when aS is co-expressed with synphilin-1.¿

The researchers are now testing whether they can manipulate the extent of Lewy body formation by crossing mice engineered to have different mutations in their three key protein inclusions.