Flip-flop around the origin and terminus of replication in prokaryotic genomes
© BioMed Central Ltd 2001
Published: 15 November 2001
A response to Evidence for symmetric chromosomal inversions around the replication origin in bacteria by JA Eisen, JF Heidelberg, O White, SL Salzberg. Genome Biology 2000, 1:research0011.1-0011.9.
Tillier and Collins  have argued that a substantial proportion of rearrangements of gene order result from recombination sites that are determined by the positions of replication forks. Their (plausible) theory is that replication forks are hot spots for recombination. Given that the two replication forks are at approximately the same distance from the origin (during the bi-directional replication), translocations are symmetrical about the origin-terminus axis. Thus, according to Tillier and Collins , specific constraints on the mechanisms of recombination are responsible for the observed bias in the frequency of finding particular rearrangement products. We argue that it is selection that may be mainly responsible for the observed bias, and the probability that a rearrangement product is viable depends on its topology.
The first aspect of topology that could lead to biased genome rearrangements is the distance of a gene from the origin of replication, as this determines the relative copy number of the gene in each cell of fast-growing cultures of bacteria. If the generation time is shorter than the replication period, the number of copies of genes lying near the origin is higher than the number of copies of genes lying near the terminus. Thus, selection pressure leads to the optimal position of genes with respect to the distance from the origin of replication [6,7]. As a result, as well as observing a bias towards specific rearrangements, there is an asymmetry in the nucleotide composition of gene sequences and a biased amino-acid composition of proteins encoded by genes along the chromosome .
The third selection force that could lead to biased rearrangements might be the trend towards keeping both replichores the same size (see also ). If there is a selection pressure ensuring that the length of the two replichores in prokaryotic genomes stays almost the same, inversions symmetrical in respect to origin or terminus of replication ought to be preferred. Figure 3b shows how a recombination event encompassing the origin of replication but with the origin not in the center of the inverted fragment generates replichores of different length and changes the distances from the origin to genes lying outside the inverted sequence.
All of the above explanations do not exclude the possibility that there are hot spots of recombination connected with the replication forks, as suggested by Tillier and Collins , but we would like to stress that selection probably plays a very important role in producing the strange X image of translocation topology in closely related genomes.
Jonathan A Eisen responds:
I welcome the letter by Mackiewicz et al. relating to whole-genome X-alignments (which we refer to as X-files). I agree that selection is likely to be a contributing factor in the observations, on the basis of comparative genomics, that the distance a gene is from the origin of replication is maintained over evolutionary time [1,2,4]. Their suggestions for possible selective forces are all entirely reasonable, and it will be worth pursuing the contribution of each in future work. I would like to point out a few additional issues relating to the X-files, however. First, it is important to note that some very important work on this subject has been done using genetic approaches [6,7,14,15,16,17,18,19,20]. As pointed out in some of these studies and by Mackiewicz et al., the presence of selection does not necessarily mean that mutation processes are not also an important contributing factor. It is likely that some type of mutation bias (such as strand switching during replication, as suggested by Tillier and Collins ) leads to a high frequency of inversions that are symmetric around the origin of replication. Many other inversions are also likely to occur. Thus, negative selection (such as selection against changes in replichore size or gene dosage, as suggested by Mackiewicz et al.) is likely to then cause the inversions that are observed over evolutionary time to be predominantly those that are symmetric around the origin of replication. What we now need from a scientific point of view is more information on frequencies and types of genome inversion that occur in the absence of selection, as well as information on the fitness differences between strains with different inversions.
In addition, I would like to comment on the suggestion that the observation of the X-alignment pattern can aid in making functional predictions for genes. Mackiewicz et al. suggest that if one finds homologous genes at the same distance from the origin of replication one can conclude that they have the same function. I would suggest this is not a good functional prediction criteria. As discussed previously , within individual genomes, pairs of paralogous genes are frequently found on both sides of the replication origin at equal distances (leading to a within-genome X pattern). We proposed that this is likely to be due to inversions that split tandemly duplicated paralogous genes. Because one or both of these genes may have diverged in function from that of a common ancestor, their position from the replication origin will not help in predicting their function when compared to other species. In addition, as orthologous genes do not always have the same function, even without the occurrence of tandem duplications, genome location alone is not likely to be a reliable predictor of gene function. Thus, while I believe the X-alignment pattern may reveal a great deal about mutation and selection pressures relating to inversions and genome position, I am not convinced that the function of a gene can be readily predicted by identifying homologous genes equidistant from replication origins.
Jonathan A Eisen
The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA. E-mail: firstname.lastname@example.org
Our work is supported by The State Committee for Scientific Research, grant numbers 6 P04A 025-18 and 6 P04A 016 20. P.M. was supported by the Foundation for Polish Science.
- Eisen JA, Heidelberg JF, White O, Salzberg SL: Evidence for symmetric chromosomal inversions around the replication origin in bacteria. Genome Biol. 2000, 1: research0011.1-0011.9. 10.1186/gb-2000-1-6-research0011. [http://genomebiology.com/2000/1/6/research/0011/]View ArticleGoogle Scholar
- Suyama M, Bork P: Evolution of prokaryotic gene order: genome rearrangements in closely related species. Trends Genet. 2001, 17: 10-13. 10.1016/S0168-9525(00)02159-4.PubMedView ArticleGoogle Scholar
- Read TD, Brunham RC, Shen C, Gill SR, Heidelberg JF, White O, Hickey EK, Peterson J, Utterback T, Berry K, et al: Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39. Nucleic Acids Res. 2000, 28: 1397-1406. 10.1093/nar/28.6.1397.PubMedPubMed CentralView ArticleGoogle Scholar
- Tillier ER, Collins RA: Genome rearrangement by replication-directed translocation. Nat Genet. 2000, 26: 195-197. 10.1038/79918.PubMedView ArticleGoogle Scholar
- Blattner FR, Plunkett G III, Bloch CA, Perna NT, Burland V, Riley M, Collado-Vides J, Glasner JD, Rode CK, Mayhew GF, et al: The complete genome sequence of Escherichia coli K-12. Science. 1997, 277: 1453-1462. 10.1126/science.277.5331.1453.PubMedView ArticleGoogle Scholar
- Liu SL, Sanderson KE: Rearrangements in the genome of the bacterium Salmonella typhi. Proc Natl Acad Sci USA. 1995, 92: 1018-1022.PubMedPubMed CentralView ArticleGoogle Scholar
- Liu SL, Sanderson KE: Highly plastic chromosomal organization in Salmonella typhi. Proc Natl Acad Sci USA. 1996, 93: 10303-10308. 10.1073/pnas.93.19.10303.PubMedPubMed CentralView ArticleGoogle Scholar
- Mackiewicz P, Gierlik A, Kowalczuk M, Dudek MR, Cebrat S: How does replication-associated mutational pressure influence amino acid composition of proteins?. Genome Res. 1999, 9: 409-416.PubMed CentralGoogle Scholar
- Frank AC, Lobry JR: Asymmetric substitution patterns: a review of possible underlying mutational or selective mechanisms. Gene. 1999, 238: 65-77. 10.1016/S0378-1119(99)00297-8.PubMedView ArticleGoogle Scholar
- Tillier ER, Collins RA: Replication orientation affects the rate and direction of bacterial gene evolution. J Mol Evol. 2000, 51: 459-463.PubMedGoogle Scholar
- Szczepanik D, Mackiewicz P, Kowalczuk M, Gierlik A, Nowicka A, Dudek MR, Cebrat S: Evolution rates of genes on leading and lagging DNA strands. J Mol Evol. 2001, 52: 426-433.PubMedGoogle Scholar
- Tatusov RL, Natale DA, Garkavtsev IV, Tatusova TA, Shankavaram UT, Rao BS, Kiryutin B, Galperin MY, Fedorova ND, Koonin EV: The COG database: new developments in phylogenetic classification of proteins from complete genomes. Nucleic Acids Res. 2001, 29: 22-28. 10.1093/nar/29.1.22.PubMedPubMed CentralView ArticleGoogle Scholar
- National Center for Biotechnology Information. [ftp://ftp.ncbi.nlm.nih.gov]
- Segall AM, Roth JR: Recombination between homologies in direct and inverse orientation in the chromosome of Salmonella : intervals which are nonpermissive for inversion formation. Genetics. 1989, 122: 737-747.PubMedPubMed CentralGoogle Scholar
- Schmid MB, Roth JR: Selection and endpoint distribution of bacterial inversion mutations. Genetics. 1983, 105: 539-557.PubMedPubMed CentralGoogle Scholar
- Segall A, Mahan MJ, Roth JR: Rearrangement of the bacterial chromosome: forbidden inversions. Science. 1988, 241: 1314-1318.PubMedView ArticleGoogle Scholar
- Mahan MJ, Roth JR: Ability of a bacterial chromosome segment to invert is dictated by included material rather than flanking sequence. Genetics. 1991, 129: 1021-1032.PubMedPubMed CentralGoogle Scholar
- Mahan MJ, Roth JR: Reciprocality of recombination events that rearrange the chromosome. Genetics. 1988, 120: 23-35.PubMedPubMed CentralGoogle Scholar
- Francois V, Louarn J, Patte J, Rebollo JE, Louarn JM: Constraints in chromosomal inversions in Escherichia coli are not explained by replication pausing at inverted terminator-like sequences. Mol Microbiol. 1990, 4: 537-542.PubMedView ArticleGoogle Scholar
- Rebollo JE, Francois V, Louarn JM: Detection and possible role of two large nondivisible zones on the Escherichia coli chromosome. Proc Natl Acad Sci USA. 1988, 85: 9391-9395.PubMedPubMed CentralView ArticleGoogle Scholar