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Studies of meiotic recombination have revealed an evolutionary paradox. Molecular and genetic analysis has shown that crossing over initiates at specific sites called hotspots, by a recombinational-repair mechanism in which the initiating hotspot is replaced by a copy of its homolog. We have used computer simulations of large populations to show that this mechanism causes active hotspot alleles to be rapidly replaced by inactive alleles, which arise by rare mutation and increase by recombination-associated conversion. Additional simulations solidified the paradox by showing that the known benefits of recombination appear inadequate to maintain its mechanism. Neither the benefits of accurate segregation nor those of recombining f lanking genes were sufficient to preserve active alleles in the face of conversion. A partial resolution to this paradox was obtained by introducing into the model an additional, nonmeiotic function for the sites that initiate recombination, consistent with the observed association of hotspots with functional sites in chromatin. Provided selection for this function was sufficiently strong, active hotspots were able to persist in spite of frequent conversion to inactive alleles. However, this explanation is unsatisfactory for two reasons. First, it is unlikely to apply to obligately sexual species, because observed crossover frequencies imply maintenance of many hotspots per genome, and the viability selection needed to preserve these would drive the species to extinction. Second, it fails to explain why such a genetically costly mechanism of recombination has been maintained over evolutionary time. Thus the paradox persists and is likely to be resolved only by significant changes to the commonly accepted mechanism of crossing over.Meiotic crossing over between homologous chromosomes plays two important roles in the genetic reshuffling caused by sexual reproduction: it creates new combinations of alleles within each chromosome, and it prevents nondisjunction during chromosome segregation (1). Crossovers are initiated primarily at specific sites called hotspots (2, 3). Most studies of the mechanism have been done in ascomycete fungi, where meiosis can be synchronously induced and all the meiotic products recovered in the ascus. Biased gene conversion is a typical consequence of recombination at hotspots (4-6). For example, a cross between active and inactive alleles of the ARG4 hotspot in the yeast Saccharomyces cerevisiae exhibits a 22-fold bias toward conversion of the active allele to its inactive homolog (6). Physical studies have shown that recombination events in S. cerevisiae are initiated by site-specific doublestrand DNA breaks at hotspots, before the visible pairing of the chromosomes (7, 8). As illustrated in Fig. 1, these breaks are thought to be repaired by DNA synthesis that uses the strands of the homologous chromosomes as templates, with resolution of the repair intermediate frequently creating a crossover between the participating chromosomes (9, 10). This and rela...

Many bacteria are naturally competent, able to actively transport environmental DNA fragments across their cell envelope and into their cytoplasm. Because incoming DNA fragments can recombine with and replace homologous segments of the chromosome, competence provides cells with a potent mechanism of horizontal gene transfer as well as access to the nutrients in extracellular DNA. This review starts with an introductory overview of competence and continues with a detailed consideration of the DNA uptake specificity of competent proteobacteria in the Pasteurellaceae and Neisseriaceae. Species in these distantly related families exhibit strong preferences for genomic DNA from close relatives, a self-specificity arising from the combined effects of biases in the uptake machinery and genomic overrepresentation of the sequences this machinery prefers. Other competent species tested lack obvious uptake bias or uptake sequences, suggesting that strong convergent evolutionary forces have acted on these two families. Recent results show that uptake sequences have multiple "dialects," with clades within each family preferring distinct sequence variants and having corresponding variants enriched in their genomes. Although the genomic consensus uptake sequences are 12 and 29 to 34 bp, uptake assays have found that only central cores of 3 to 4 bp, conserved across dialects, are crucial for uptake. The other bases, which differ between dialects, make weaker individual contributions but have important cooperative interactions. Together, these results make predictions about the mechanism of DNA uptake across the outer membrane, supporting a model for the evolutionary accumulation and stability of uptake sequences and suggesting that uptake biases may be more widespread than currently thought. N aturally competent bacteria actively pull DNA fragments from their environment into their cells. These fragments provide nucleotides, but high similarity with the chromosome also allows them to change the cell's genotype by homologous recombination, a process called natural transformation ( Fig. 1; reviewed in references 1, 2, 3, 4, and 5). Most competent bacteria that have been tested can take up DNA from any source, but species in two distantly related families of Gram-negative bacteria, the Pasteurellaceae and the Neisseriaceae, show strong preferences for DNAs containing short sequences that are highly overrepresented in their own genomes, leading to preferential uptake of conspecific DNA (6). This self-specificity both raises questions about and provides a tool for investigating the evolution of competence and the mechanism of DNA uptake.We begin with a general overview of competence, emphasizing the evolutionary issues. We then describe the two components that together create self-specificity, sequence biases in the DNA uptake machinery and overrepresentation of uptake sequences in the genomes, highlighting recent work on the mechanism and evolution of uptake biases in the two families and an evolutionary model that accounts for upt...

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