Processes of molecular evolution

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and eukaryotes remains to be seen13. Nevertheless, Michod et a/.‘s3 experiment supports the idea that the evolutionary significance of natural transformation lies in its capacity to repair damaged DNA. Recent computer simulation models14 that explore the effects of transformation on mutation load draw a similar conclusion. These simulations indicate that naturally transforming populations of bacteria undergoing deleterious mutation and selection are always fitter at equilibrium than asexual populations. As Rosemary Redfield’ remarks, it may be better for bacteria to have sex with a dead cell than to have no sex at all.

References 1 Watson, J.D., Hopkins, N.H., Roberts, J.W., Steitz, J.A. and Weiner,A.M. (1987) The Molecular Biologyofthe edn), Beniamin Cummings

Gene (4th

2 Bernstein, H., Hopf, F.A: and Michod, R.E. (1987) Adv. Genet. 24.323-370 3 Michod,‘R.E., Wodjciechowski, M.F. and Hoelzer, M.A. (1988) Genetics1 18,31-39 4 Stewart, G.J. and Carlson, CA. (1986)

John Brookfield is at the Department of Genetics, Queen’s Medical Centre, Nottingham NG7 2UH, UK and Paul Sharp is at the Department of Genetics, Trinity College, Dublin 2, Republic of Ireland.

8 Yasbin, R.E. (1985) in T/te Molecular BiologyoftheBacilli, Vol. //(Dubnau, D.A. ed.), pp. 33-52, Academic Press 9 Walker, G.C. (1984) Microbial. Rev. 48, 60-93 10 Levin, B.R. (1987) in TheEvolution of Sex(Michod, R.E. and Levin, B.R.,eds),pp 194-211,Sinauer 11 Bernstein. H,, Byerly, H.C., Hopf, F.A.

and Michod, R.E. (1985) Science 229, 1277-1281

12 Bernstein, H., Hopf, F.A. and Mlchod, R.E. (1987) in TheEvolution ofSex (Michod, R.E. and Levin, B.R., eds), pp 139-160, Sinauer 13 Maynard Smith, J. (1987) in The

ed.), pp. 147-178, Academic Press 7 Smith, H.O., Danner, D.B. and Deich, R.A. (1981)Annu. Rev. Biochem. 50,

EvolutionofSex(Michod, R.E. and Lewn. B.R., eds), pp, 106-125, Sinauer 14 Redfield, R.J. (1988) Genetics 119, 213-221

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John F.Y.Brookfieldand PaulM. Sharp IN EVOLUTION makes sense except in the light of populations’. With this adaptation of Dobzhansky’s well-known dictum, G. Dover (Cambridge) opened the recent EMBO workshop on Processes of Molecular Evolution. The workshop (organized by G. Dover and R. Flavell, and held in Cambridge, UK, 4-6 July 1988) brought together an international group of 90 molecular biologists, geneticists and evolutionary biologists to discuss the latest advances in molecular evolutionary studies. As the workshop’s title and Dover’s opening remark implied, the intended emphasis of the discussions was to be on the way in which molecular evolution works: does the rapidly growing body of molecular data yet allow us to discern process in the patterns? Several contributions focused on the extent to which we can infer back from current biochemical processes to the nature of life in or before the earliest cells. N. Maizels and A. Weiner (Yale) used the term ‘molecular fossils’ for nucleic acids whose present structures might provide insight into their functions when they first arose. For example, Maizels suggested that the earliest ancestors of tRNAs served as telomeres and initiation sites (‘genomic tags’) for replication on RNA molecules in the pre-DNA world. According to W. Gilbert (Harvard), introns may also be

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Annu. Rev. Microbial. 40,21 l-235 5 Spizizen, J. (1958) Proc. Nat/ Acad. So. USA44,1072-1078 6 Dubnau, D. (1982) in TheMolecular BiologyoftheBacilli, Vol. I(Dubnau, D.A.,

Processes ofMolecular Evolution ‘NOTHING

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‘fossils’ of a kind: a finite number of ‘ur-genes’, each 15-20 codons long and encoding a mini-element of protein structure, may have been assembled to form the great diversity of longer genes found in contemporary genomes. These introns have subsequently been exploited, for example in allowing shuffling of the ur-genes (now exons), as illustrated by S. Holland’s (Oxford) discussion of mammalian serine protease genes. This suggests a potential pitfall for palaeontologists of the genome in that molecules, unlike real fossils, remain as parts of living processes, their structure determined by current function as well as by their evolutionary history. Debate arose as to what proportion of introns may represent subsequent additions to genes. J. Rogers (Cambridge) indicated a myriad of cases where introns in homologous genes lie in slightly different positions. This might be interpreted as evidence for intron sliding, but Rogers pointed out that such a mechanism raises real problems when the intron positions differ by a non-integral number of codons and/ or lie on opposite sides of conserved amino acids. Another question mark concerns the generality of the location of introns between domainit encoding sequences; was suggested that this may merely reflect a tendency for insertion to occur away from the ends of existing exons. Another topic dealt with in considerable detail was the nature of genetic sequences found in organelles. It is clear that mitochon-

drial DNAintrons in yeastaredifferent in kind from nuclear introns (in that there is population variation for their presence or absence), that they are capable of self-splicing in vitro, and that many encode ‘nucleic acid wielding’ proteins (L. Grivell, Am sterdam and P. Slonimski, Gif-surYvette). Organelle genomes are much reduced in coding capacity compared to prokaryotes the thought to resemble their ancestors, partly through transfer of sequences to the nuclear genes. J. Palmer (Ann Arbor) showed cases where, by phylogenetic comparisons, it is possible to infer the time when chloroplast genes moved to the nucleus it! particular lineages. The physical transfer of DNA in such events i:~ quite easy to imagine, but what is more problematic is how the translo cated genes acquire eukaryotic tran scription control sequences and Ia chloroplast transit peptide domain to enable their products to re-enter the organelle. One revelatlon of molecular blol ogy has been the extent to which genes exist In families. T. Ohta (Mishima) has rnodeled the evol ution of a diverging multigene family under conditions of unequal crossselection mutation and over, Perhaps the most revealing aspect of her simulations was the very high variation between replicates, irn~ plying for example that differences among families in copy number and proportion of non-functional men-ibers (pseudogenes) may be largely due to chance. N. Maeda (Chapel Hill) revealed that in human populations the haptoglobin genes exhibit duplication polymorphism, with Individual haplotypes containing front two to seven copies. In these and other situations the mechanisms of unequal crossing over and gene con

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version can lead to gene family members evolving in concert. Dover has extended these ideas through ‘molecular drive’ to address apparently puzzling examples of molecular coevolution. These involve the increase in frequency of secondary mutations that compensate for others that have already spread through a gene family. These compensating mutations may occur in other genes or even within the same molecule, as in mutations restoring secondary structure in the 28s rRNA genes of Drosophila. Of 3ourse, a large puzzle remains: if drive can overcome selection and spread a weakly deleterious mu:ation through a repeat array, why should the correspondingly weak selective advantage of a compensatng mutation be able to ensure its ;pread? Another puzzle surrounds the con:;ervation of within-family similarity of interspersed repeated sequences, twhich may not be undergoing I egular concerted evolution. Rather, repeated generation of new family members by transposition, and a corresponding loss of old members, may be sufficient explanation. The question remains as to how many members can act as templates for the generation of new members. R. Britten (Caltech) reported the results of an analysis of more than 300 I:opies of the primate A/u SINE sequence. Divergences between the sequences strongly suggest that cunly one or a few (up to four) genes llave acted as sources for all the A/us

THE ABSTRACT CASE of an crganism that moves around to find food. Imagine also that food is not homogeneously distributed and that the local renewal rate is slow, so that as the organism stays in the same place the rate at which it acquires food drops. How should we expect this animal to move about its habitat in response to food distribution? Nearly fifteen years ago, Smith1 argued that the rate of predator movement should decrease after c$jpturing prey, leading to a slower transit through areas of higher prey density. Exactly how much slower the movement should be could not b: solved at that time. More recent (:ONSIDER

- there has apparently been little repeated transposition of these sequences. Conspicuously, the meeting was almost completely unconcerned with the neutralist-selectionist debate, which has dominated so much of the discussion of molecular evolution over the last 20 years. However, the molecular clock, so often mentioned in the same breath as the neutral theory, did provoke some controversy. A. Wilson (Berkeley) suggested that the basic rate of evolution, as revealed by substitutions at silent sites, is approximately the same in all DNA genomes (excluding those in organelles) from E. co/i to humans. Wilson argued against the majority view that molecular clocks (for silent DNA substitutions) tick faster in some organisms (notably rodents and fruitflies) than in others (in particular, primates), on the grounds that the former have very poor fossil records; phylogenetic splits among, for instance, rodents, might have been given inaccurately recent dates. There does, however, seem to be no good theory that might predict such universal constancy of the molecular evolutionary rate in the face of the enormous variability of mutation rate and effective population size in different organisms. In fact, silent sites often evolve at different rates, even in genes in the same organism. To link DNA sequences to organismal morphology may be the ultimate grail of evolutionary biologists. We have always known that develop-

mental processes will constrain the phenotypes that organisms may show, but have been unable to incorporate such constraints into evolutionary theory since nobody understood them. Now, in work described by A. Garcia-Bellido (Madrid) and A. Martinez-Arias (Cambridge), we are beginning to understand the logic of animal development, at least in Drosophila. One specific suggestion from E. Coen (Norwich) was that, at least in the short term, morphological evolution may often occur by changes in the binding capabilities of c&acting regulatory sequences. F. Kafatos (Harvard) showed that for the silkmoth and fruitfly chorion genes it is possible to dissect precisely, by reverse genetics, the evolution of function of such sequences, and indeed in some cases to show the morphological consequences of such evolution. As the meeting showed, the pace of discovery at the molecular level is generating a great deal of excitement and speculation. It is difficult, however, to do experiments in molecular evolution, and this is why so much of the discussion at this meeting concerned pattern and description. Hypothesis testing in this field is usually carried out by comparative studies. Thus, one question for the future of molecular evolution is whether more effort can be channelled into manipulating the subject material. A closer alliance between molecular evolutionary studies and population genetics will surely prove fruitful.

Distributions: Patch Models Gaina Lease ofLife AlejandroKacelnikand CarlosBernstein

work on foraging used the simplifying assumption that food is distributed in patches, namely clumps separated by areas with no food at all. Animals can either forage within a patch or travel between patches. For example, in a classic study, Krebs, Ryan and Charnov* analysed of Blackcapped chickA ejandro Kacelnik is at the King’s College Re- movements search Centre, King’s College, Cambridge CB2 adees (farm atricapillus) in a patchy and discussed the lST, UK, and Carlos Bernstein is at the Dept de environment Blologie Generale et Apliquke, Laboratoire de optimal rule for departure time from theoretical Blometrie, Universitb Claude Bernard, Lyon 1, each patch. Influential papers3s4 also considered patchy disF--69622Villeurbanne Cedex, France.

tribution of resources and, using the now classical Marginal Value Theorem (MVT), rigorously defined the optimal emigration policy, namely when to leave a patch and move to another one. Although in practice informational constraints affect the choice of optimal policy (see Stephens and Krebs’5 illuminating and comprehensive review), the general solution is conceptually very simple. The maximum rate of energy intake is achieved by remaining in the same