by Greg Gibson

There is growing crosstalk between evolutionary and developmental biologists. They are using the strengths of their respective disciplines, i.e. descriptive cataloging and experimental manipulation, as well as the tools of molecular biology and genome science. Thus knowledge about molecular structures is now being applied to study not only the patterns of life-forms, but how they evolve.

A classical little Bavarian town nestled high in the Alps, Garmisch-Partenkirchen is near the internationally known Oberammergau passion play. This summer it was the scene of a scientific passion play. Molecular evolutionists are an eclectic bunch, perhaps still struggling to find an identity, but they do know how to meet in odd places to discuss what molecules have to say about evolution. The Society for Molecular Biology and Evolution (SMBE), founded just five years ago, alternates meetings between North America and the rest of the world each year. So far this plan has been very effective, for approaches to molecular biology and evolution are diverse and somewhat geographically distinct. Germany has always been known for the development of practical technology, and in evolutionary circles for comparative and experimental embryology. Both of these themes were strongly imprinted on the SMBE V conference, which highlighted our increasing understanding of genome diversity, its generation, and its implications.

The Society was conceived in the early 1980s to foster communication among those who wish to "critically examine the evolutionary significance of macromolecules." But what does this mean? To examine how macromolecules evolve, perhaps, or maybe to use macromolecules to examine how other things, such as taxa, evolve? Both, it turns out, and more. With the birth of subdisciplines such as genome science and developmental evolution, it has become clear that molecular biology can be used to study even the evolution of organisms. SMBE is thus in a time of transition, from using molecules to study the pattern of life to using them to make inferences about evolutionary processes. This is a rich development, and was an evident theme in Garmisch-Partenkirchen.

These new trends notwithstanding, phylogenetics has been the bread and butter of molecular evolution for the past decade, and will continue to remain central to the discipline. There is still much to learn about taxonomy, from sorting out the basal relationships within kingdoms, and even phyla, to inferring the histories of particular human populations. No meeting of systematists would be complete without a public airing of disagreements, and this one had its share. Luca Cavalli-Sforza of the Department of Genetics at Stanford University did his best to moderate any disputes with a call for diversity of data in attacking a range of problems. He did so both from the floor and in the context of two talks, one delivered slide-free in an effort to help us focus on his arguments. He reinforced consensus by noting that gene trees are neither taxon trees nor guaranteed truth. What they are, especially when interpreted with due caution and constructed with the latest favored software packages, are maximum likelihood statements about historical relationships among gene sequences. If several data sets give the same pattern, well and good, but if not, then perhaps they are saying something interesting about the evolution of the particular genes.

Though not gathered into a single symposium, talks throughout the meeting touched on the opportunities this increasingly common situation opens for biologists. Chip Aquadro of Cornell University, for example, gave a very sobering talk about the genome-wide processes that regulate rates of sequence evolution. Recombination rates are clearly a major factor, since levels of polymorphism within many species are strongly correlated with chromosomal location, whence with crossover frequency. Several speakers touched on statistical methods for comparing rates of evolution within and between lineages, and it is good to remember that these reflect things going on at the population level - things just as likely to be neutral as adaptive. In a similar vein, considerable attention was paid to molecular biological approaches to the study of mutation mechanisms (see also the debate on optimal mutation rates in this issue of HMS Beagle).

Alan Weiner of Yale University and Rodney Rothstein of Columbia University presented thought-provoking data on mechanisms of concerted evolution, such as gene conversion and unequal recombination, in repetitive gene arrays. All of which was music to the ears of Gabby Dover of the University of Leicester; he took several opportunities to remind us that he has claimed for years that molecules drive their own rates of sequence evolution. What must be added to this perspective is the further realization that molecular events far removed from gene function - such as recombination rates, the degree of synteny (gene alignment between divergent taxa), and genome-wide levels of duplication - might be a large source of discrepancy between phylogenies.

The organizers were also at pains to bring together a variety of speakers to discuss how molecular genetic analyses are beginning to uncover the mechanisms of organismal evolution. A symposium on development and evolution featured two comparative molecular anatomists and a couple of quantitative developmental geneticists. Nipam Patel of the University of Chicago showed beautiful slides of myriad crustacean embryos and their tropical home off the Belizean cayes, and told a marvelous story about the changes in regulatory gene expression that accompany, and presumably cause, changes in the body plan. Did you ever wonder, butter dripping from your fingers, how lobsters come to have different limbs when they're babies and before you eat them? It is in large part because the domains of homeotic gene expression change between larval stages - and a similar phenomenon helps to explain why other arthropods have such a diversity of legs and mandibles.

What constrains and potentiates these shifts in gene expression is ultimately a question for population and quantitative genetics. Trudy Mackay of the North Carolina State University Department of Genetics summarized her pathbreaking work on the molecular basis of variation in a model continuous trait, the number of bristles on a fly. For the first time, names can be given to statistical geneticists' arithmetic QTLs (quantitative trait loci), and they satisfyingly turn out in many cases to be the same genes that when removed completely have major effects on bristle development. Such results raise the genuine hope that modern developmental genetics and classical evolutionary genetics, separated but not divorced for almost 50 years, will soon reunite. Further, it is increasingly clear that the handful of genes that have major effects on continuous traits generally harbor multiple functionally significant polymorphisms in natural populations. Perhaps the time is not too distant when we will be able to identify the nucleotide changes that quantitatively affect morphology.

Another mechanistic symposium was dedicated to in vitro evolution, where in vitro is defined as E. coli, catalytic RNAs, and computer simulations. David Bartel of the Whitehead Institute, Cambridge, Massachusetts, generated much astonishment with his presentation about the creation and evolution of new ribozymes. These are of interest to more than chemical companies looking to manufacture novel catalytic activities, for they are clearly relevant to the empirical and reductionist dissection of evolutionary phenomena. Taken together with the talk of Rob Dorit of the Yale University Department of Ecology and Evolutionary Biology, it is becoming apparent that simple sequences can be rather clever. They can evolve cooperative behavior, for example, implying that nonselfishness may have a long history on this planet. It will be fascinating to see how these intellectual approaches are applied to the analysis of compensatory changes in protein evolution, and to the coevolution of gene products.

Just as clearly, technology is changing the way science, including evolutionary biology, is done. A workshop was devoted to new sequencing methods, and the final symposium was handed over to genome people. We were wowed by the pace and scale of human genome sequencing efforts, though some could be excused for disbelieving that an accuracy of 0.1% is routine after observing that St. Louis is near Detroit and Stanford in Los Angeles on one speaker's map of international genome centers. There is no doubt that sequencing on this scale is informative - ironically not because it provides more "characters" (nucleotide changes) for phylogenetic reconstruction, but rather because it sieves out the rare events that can be relied upon to provide an unambiguous signal. If there was any doubt that simply getting more sequence cannot resolve difficult issues, it must have been dispelled by Hans-Peter Klenk's (The Institute for Genome Research) analysis of TIGR's complete microbial genome sequences: different classes of gene give different relationships between archaebacteria, eubacteria and eukaryotes, and there is no simple resolution of the trichotomy (see the June 27, 1997 issue of Cell for a collection of reviews on this topic).

Rather, genome analysis is providing much needed information on the diversity and alignment of low copy number sequences. Puffer fish enthusiasts, who have always had some explaining to do anyway, will not be pleased with new data showing that groups of genes that are syntenic between mice and humans are very much broken up in the teleost with the small genome. On the other hand, they may make the claim that this opens up the possibility of using gene order as a source of information in taxonomic reconstruction, pointing to Jeff Boore's (University of Michigan, Department of Biology) exciting use of gene order inferred from whole mitochondrial genome sequencing to address numerous issues in protostome phylogeny.

One of the other things that has characterized the meetings of the youthful SMBE has been a commitment to young scientists. Graduate students were specifically recognized with a long symposium highlighting their talents and resulting in the award of the Walter Fitch Prize for the best young investigators - an award the judges found wonderfully difficult to make. For postdocs, the meeting in Japan two years before was followed by an excellent binational workshop between Japanese and American molecular evolutionists. Similarly, this year's meeting was followed by a trinational workshop including Europeans, and we can only hope that the meeting in 1999 in Brisbane will continue the trend. Perhaps there too some of the local flavor will permeate the meeting, and the Australian enthusiasm for ecology will begin to add to the new modern synthesis of molecular biology and evolution.

Greg Gibson is an assistant professor in the Department of Biology at the University of Michigan in Ann Arbor.

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Endlinks

Evolutionary Biology, Molecular Phylogenetics and Epidemiology - a Web site containing software programs for DNA and protein sequence analysis, including some that evaluate evolutionary relationships.

The Organelle Genome Megasequencing Program - an interdisciplinary collaboration among research groups in eastern Canada, each of which is interested in molecular evolution, with a major focus on mitochondria, plastids and bacteria.

The National Center for Science Education - sponsors the Human Evolution Education Network to bring together K-12 science teachers and scientists whose expertise is human evolution. The HEEN Web page lists publications of their own project and other resources for evolution and biology education, online and offline.

Two articles by Elizabeth Pennisi and Wade Roush address the interdisciplinary nature of this field. In the first they describe the recent advances in knowledge of early embryology by the merging of efforts by developmental biologist and evolutionists. In the second, the authors describe some of the challenges facing researchers in this hybrid of disciplines. Each requires a paid subscription to Science magazine.

Pennisi, E. and Roush, W. 1997. Developing a new view of evolution. Science 277:34-37.

Pennisi, E. and Roush, W. 1997. Growing pains: Evo-Devo researchers straddle cultures. Science 277:38-39.

See also the Internet sites recommended in this issue's Optimum Mutation Rate in Evolution and Disease debate.