Do Bacteria Have Sex? Ticket to Be a Winner
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PERSPECTIVES und ihre Anwendung auf die Abderhalden’schen (Cold Spring Harbor Laboratory Press, New York, 1998). Abwehrfermentreaktion. Hoppe-Seyler’s Zs für 13. Posner, G. L. & Ware, J. Mengele. The Complete Story. vived. Even if harmful exchange events were physiologische Chemie 277, 222–232 (1943). (McGraw–Hill, New York, 1986). 100-fold more common than beneficial ones, 12. Müller-Hill, B. Tödliche Wissenschaft. Die Aussonderung von Juden, Zigeunern und Geisteskranken. (Rowohlt, Acknowledgements we would only see the latter in genomes today. Reinbek, 1984). English translation: Murderous Science. I thank the Präsidentenkommission of the Max-Planck- So, finding transferred genes in modern Elimination by Scientific Selection of Jews, Gypsies and Gesellschaft (MPG) for giving me access to the letters of Others in Germany 1933–1945 (Afterword by J. Watson) Butenandt and the Archive of the MPG for their excellent help. genomes shows that some transfers, like some mutations, are adaptive, but this finding does not address the larger issue of the average costs and benefits of exchange. Filtering by natural selection is like the fil- OPINION tering of lottery outcomes by the media. On the basis of what we read in the newspapers, we would expect everyone who buys a lottery Do bacteria have sex? ticket to be a winner. Of course, most scien- tists know better than to buy lottery tickets, Rosemary J. Redfield but many have failed to apply the same logic to the processes that generate genetic diversi- Do bacteria have genes for genetic CONJUGATION or TRANSFORMATION, and can be ty. Research papers do not explicitly claim that exchange? The idea that the bacterial physically recombined into their chromo- genetic exchange must be adaptive because processes that cause genetic exchange somes by various cytoplasmic proteins. The we see its benefits and not its harmful conse- exist because of natural selection for this many sequenced bacterial genomes contain quences — if this were done, the error would process is shared by almost all abundant examples of genes that were unam- be obvious. Nevertheless, the error is probably microbiologists and population geneticists. biguously acquired by horizontal transfer. responsible for much of the complacency However, this assumption has been For example, most of the physiologically with which most biologists view the evolution perpetuated by generations of biology, important differences between Escherichia of genetic exchange. microbiology and genetics textbooks coli and Salmonella typhimurium result from without ever being critically examined. recombination: genes for lactose, citrate and Rigorous approaches to sex propanediol use, and indole production, have Until recently, scientific approaches to the Terms such as sex and recombination have all been acquired in this way4. problem of the evolution of sex have almost different meanings in different contexts. exclusively been the domain of theoretical Here, I use recombination to mean the How not to study selection for sex population genetics. The formulation of breaking and joining of DNA strands; genetic Because the ability to create new genetic com- explicit mathematical statements is a rigor- exchange, gene transfer or HORIZONTAL TRANS- binations affects FITNESS only indirectly and ous tool for evolutionary analysis, but this FER to refer to processes that produce new because the outcomes are intrinsically unpre- rigour often demands a corresponding sacri- genetic combinations; and meiotic sex to dictable, selection for the creation of new fice of relevance. Mathematical modelling mean the cyclical alternation between hap- genetic combinations is much harder to inves- can show how selection on the genes that loid and diploid stages in eukaryotes. Sex tigate than selection on processes that con- cause genetic exchange might act, but only refers to any process selected by the benefits tribute directly to survival or reproduction. under hypothetical and unrealistic assump- of genetic exchange. One reason why so much misunderstanding tions about the processes and their conse- Understanding the evolutionary causes of surrounds the evolution of sex is that the least quences, which are required if the equations genetic exchange in bacteria has important rigorous and most misleading evidence has are to be solvable. Computer simulations are implications for our understanding of the had the greatest influence, whereas the more versatile, as equations need not be evolution of meiotic sex in eukaryotes. The strongest has been mostly overlooked. solved but only applied repeatedly, but the primary function of meiotic sex seems to be The large number of transferred genes we assumptions that underlie the programming to produce new combinations of chromoso- find in modern bacterial genomes has misled must still be simple. For example, both theo- mal genes, but extensive work by population many researchers about the benefits of genetic retical and computer models of the evolution geneticists has been unable to show why this exchange. Many of the transferred genes are of meiotic sex often assume that all muta- would be beneficial1–3. If bacteria do have obviously beneficial to their new hosts and this tions have identical effects on fitness. As a genes that have evolved for genetic exchange, is frequently interpreted as conclusive evidence consequence, although both mathematical then they provide much-needed indepen- that gene transfer must be adaptive. The for- and computer modelling have been useful for dent systems in which to study how sex can eign origin of many of these genes is firmly showing that some explanations for meiotic evolve. If they do not, then meiotic sex must established, but the bacterial genomes that they sex are possible whereas others are not, they have evolved to provide eukaryotes with are found in are unfortunately a very biased have failed to produce solid answers2,3,5,6. benefits that are not needed by bacteria and record of evolutionary processes. The problem, The power of long-term selection experi- its evolutionary causes must be sought of course, is natural selection. Because natural ments on microbial cultures (‘experimental among eukaryote-specific phenomena. selection eliminates almost all deleterious evolution’) has only recently been appreciated7. Bacteria have several well-studied process- changes, the genomes of modern organisms These experiments tell us how selection can act es that can transfer genes, and the analysis of are the result of several billion years of evolu- under laboratory conditions, by testing experi- genome sequences has revealed that these tionary success stories, with not a single failure mentally whether a given set of conditions processes have made important contribu- represented. In a way, the sequences we see are leads to a change in the frequencies of certain tions to bacterial evolution. DNA can be a type of anecdotal evidence — each represents genotypes in a population. Because many transferred between cells by TRANSDUCTION, a unique event that has, against the odds, sur- thousands of generations can be followed, the 634 | AUGUST 2001 | VOLUME 2 www.nature.com/reviews/genetics © 2001 Macmillan Magazines Ltd PERSPECTIVES experiments can detect relatively weak selective Most bacterial recombination is ‘homolo- processes. However, a considerable limitation “The large number of gous’; that is, the two recombining segments to laboratory selection experiments is that cul- have identical or near-identical sequences ture conditions inevitably fail to reflect the evo- transferred genes we find in and base pairing between their strands lutionarily relevant conditions that are experi- modern bacterial genomes replaces one with the other. The REC PROTEINS enced by bacteria in their natural RecA and RecBCD have key roles in this environments. The problem is not that experi- has misled many researchers process, along with other proteins (RecE, menters do not wish to use natural conditions, about the benefits of genetic RecF, RecG, RecJ, RecN, RecO, RecQ, but that it is usually impossible to determine exchange.” RuvABC, Ssb, PolA, DNA ligase and DNA which features of the natural environments of gyrase A and B). Because mutations in the microorganisms are most important. genes that specify these proteins disrupt Neither theoretical nor experimental mod- recombination, the genes were often given els of evolution have shed much light on genet- What causes genetic exchange? ‘rec ’ names when first discovered. They were ic exchange in bacteria. Two models found that Bacterial genetic exchange is not like meiot- thought to function mainly in the ‘recombi- exchange could be beneficial only under condi- ic sex. Whereas meiotic sex regularly mixes nation pathways’ that were believed to have tions that were generally more restrictive than two complete sets of genes and randomly evolved to promote genetic exchange. Effects for sexual recombination in eukaryotes8,9. reassorts the alleles into new individuals, on DNA repair and overall viability were Another found that the genes that cause genet- bacterial recombinants form by processes noted, but were usually considered to be sec- ic exchange interfere with selection on the that are non-reciprocal and fragmentary, ondary. Decades of genetic and functional genes that affect mutation rates10. One well- and that are not regular components of bac- analysis have shown that DNA replication controlled selection experiment that has terial life cycles. Any one recombination and