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Concerted evolution, molecular drive and natural selection
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Concerted evolution, molecular drive and natural selection Gabby Dover Variant genetic units can spread from one chromosome to another as a result of genomic mechanisms of 'crosstalk' - unequal crossing-over, gene conversion, transposition, and so on - thus raising the probability that the variant gene will spread concomitantly through both a multigene family and a sexual population [1]. In the September issue of Current Biology, Schlotterer and Tautz [2] reported that some mutations within the 'internal transcribed space' (ITS) of the multiple ribosomal (r)DNA units in Drosophila melanogaster are chromosome-specific and coexist in the same population, leading them to the conclusion that the "original assumption and its concomitant prediction of the above model are violated". They propose that "intrachromosomal exchanges drive concerted evolution". However, there is much evidence that mutations can be either chromosome-restricted or distributed over several chromosomes, in the very same gene families [3]. For example, in contrast to the established list of chromosome-specific mutations in the rDNA of Drosophila, the 'Alu' mutation in the intergenic spacer (IGS) of the rDNA is homogenized in all examined X-chromosome and Y-chromosome rDNA arrays in world-wide populations [4], as are several other mutations revealed by digital-DNA typing [5]. Similarly, the human rDNA family contains mutations, some of which are chromosome-restricted and some of which are spread over five pairs of non-homologous chromosomes. In the human alpha-satellite DNA, some mutations are extensively homogenized to particular pairs of non-homologous chromosomes, whereas others reveal haplotypic evolution [6]. As I have argued before [7], the solution to this seeming paradox does not come by concentrating on one distribution pattern at the expense of the other. A model of homogenization within single chromosome lineages, even when coupled to drift (the 'double diffusion' of earlier models recommended for consideration by Schlotterer and Tautz [2]), cannot drive the concerted evolution of repeats located on two sex chromosomes or on multiple chromosomes. In the case of Drosophila, documented unequal exchanges between X and Y rDNA arrays must significantly contribute to this family's concerted evolution [8]. Either chromosome-specific mutations are younger mutations more rapidly homogenized, for the time being, within their own arrays, or there might indeed be physical barriers preventing them moving to other arrays [7].
Recently, the evolution of the human MS32 minisatellite DNA locus moved from being a case of single-lineage 'haplotype' evolution [9] to one of'crosstalking' multilineage evolution, following the discovery of frequent interallelic gene conversion events [10]. The precise distribution pattern of each and every mutation at any given frozen moment in time would depend on many factors involving the age of the mutation, the intrachromosomal versus interchromosomal rates of 'crosstalk', and the vagaries of chromosomal drift [11]. The interaction with selection would depend on the variance in the extent to which a variant repeat has spread in each individual in a sexual population. As stated from 1982 onwards [1,11], the maximum variance would occur in the near-absence of interchromosomal turnover, allowing chromosomes to be individually homogenized and selectable as Mendelian 'alleles', an idea re-introduced in the paper under discussion [2]. The finding of chromosome-specific mutations [2] is fascinating, and supports original proposals that homogenization occurs concurrently at different rates and at different levels. The data should not be seen as polarizing the subtle and complex factors driving concerted evolution into two seemingly opposing camps. Rather, they offer the opportunity to dissect the relative contributions of internal and external processes that underlie the evolution of genetic redundancy [3]. References 1. Dover GA: Molecular drive: a cohesive mode of species evolution. Nature 1982, 299:111-117. 2. SchlBtterer C, Tautz D: Chromosomal homogeneity of Drosophila ribosomal DNA arrays suggests intrachromosomal exchanges drive concerted evolution. Curr Biol 1994, 4:777-783. 3. Dover GA: The evolution of genetic redundancy for advanced players. Curr Opin Genet Dev 1993, 3:902-910. 4. Coen ES, Strachan T, Dover GA: The dynamics of concerted evolution of rDNA and histone gene families in the melanogaster species subgroup of Drosophila. J Mol Biol 1982, 158:17-35. 5. Ruiz Linares A, Bowen T, Dover GA: Aspects of non-random turnover involved in the concerted evolution of intergenic spacers within ribosomal DNA of D. melanogaster. I Mol Evol 1984, 39:151-159. 6. Jorgensen AL, Laursen HB, Jones C, Bak AL: Evolutionarily different alphoid repeat DNA on homologous chromosomes in human and chimpanzee. Proc Natl Acad Sci USA 1992, 89:3310-3314. 7. Dover GA: Linkage disequilibrium and molecular drive in the rDNA gene family. Genetics 1989, 122:249-252. 8. Coen ES, Dover GA: Unequal exchanges and the coevolution of X and Y rDNA arrays in D melanogaster. Cell 1983, 33:849-855. 9. Jeffreys AJ, Neumann R, Wilson V: Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism. Cell 1983, 33:849-855. 10. Jeffreys Al, Tamaki K, MacLeod A, Monckton DG, Neil DL, Armour J: Complex gene conversion events in germline mutation at human minisatellites. Nature Genet 1994, 6:136-145. 11. Dover GA, Ruiz-Linares A, Bowen T, Hancock JM: Detection and quantification of concerted evolution and molecular drive. In Methods Enzymol Edited by Zimmer EA, White TJ, Cann RL, Wilson AC. 1993, 244:525-541.
Gabby Dover, Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
© Current Biology 1994, Vol 4 No 12
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Current Biology 1994, Vol 4 No 12 Diethard Tautz and Christian Schltterer reply: We agree that some parts of our paper could be misunderstood as implying that we were proposing a new model for the phenomenon of concerted evolution. This was not our intention. Instead, what we intended to do was to provide experimental data for one of the several mechanisms that are involved in the homogenization process of multigene families. This mechanism is intrachromosomal unequal recombination. From our data, we concluded that this process must be acting relatively fast, and could thus determine the speed of the homogenization process (hence the word 'drive' in the title). The crucial part of our data is the observation that homologous chromosomes can coexist in interbreeding populations that are partially or fully homogenized for different repeat-unit variants. This indicates that there is little recombination between them while they are being
homogenized intrachromosomally. We believe that this observation goes beyond the previous demonstrations of the existence of chromosome-specific variants, and provides new information that needs to be considered when specific models are formulated. On the other hand, we fully agree with Gabby Dover that the molecular drive process as a whole is more complex and requires the full recognition of additional interchromosomal mechanisms to explain concerted evolution in toto. Also, we are aware that some of the conclusions in our paper have previously been proposed, though at the time they were only theoretical possibilities, whereas we have now provided the respective data. Diethard Tautz and Christian Schlotterer, Zoologisches Institut der Universitt Miinchen, Luisenstrasse 14, 80333 Munchen, Germany.
Concerted evolution, molecular drive and natural selection Gabby Dover Variant genetic units can spread from one chromosome to another as a result of genomic mechanisms of 'crosstalk' - unequal crossing-over, gene conversion, transposition, and so on - thus raising the probability that the variant gene will spread concomitantly through both a multigene family and a sexual population [1]. In the September issue of Current Biology, Schlotterer and Tautz [2] reported that some mutations within the 'internal transcribed space' (ITS) of the multiple ribosomal (r)DNA units in Drosophila melanogaster are chromosome-specific and coexist in the same population, leading them to the conclusion that the "original assumption and its concomitant prediction of the above model are violated". They propose that "intrachromosomal exchanges drive concerted evolution". However, there is much evidence that mutations can be either chromosome-restricted or distributed over several chromosomes, in the very same gene families [3]. For example, in contrast to the established list of chromosome-specific mutations in the rDNA of Drosophila, the 'Alu' mutation in the intergenic spacer (IGS) of the rDNA is homogenized in all examined X-chromosome and Y-chromosome rDNA arrays in world-wide populations [4], as are several other mutations revealed by digital-DNA typing [5]. Similarly, the human rDNA family contains mutations, some of which are chromosome-restricted and some of which are spread over five pairs of non-homologous chromosomes. In the human alpha-satellite DNA, some mutations are extensively homogenized to particular pairs of non-homologous chromosomes, whereas others reveal haplotypic evolution [6]. As I have argued before [7], the solution to this seeming paradox does not come by concentrating on one distribution pattern at the expense of the other. A model of homogenization within single chromosome lineages, even when coupled to drift (the 'double diffusion' of earlier models recommended for consideration by Schlotterer and Tautz [2]), cannot drive the concerted evolution of repeats located on two sex chromosomes or on multiple chromosomes. In the case of Drosophila, documented unequal exchanges between X and Y rDNA arrays must significantly contribute to this family's concerted evolution [8]. Either chromosome-specific mutations are younger mutations more rapidly homogenized, for the time being, within their own arrays, or there might indeed be physical barriers preventing them moving to other arrays [7].
Recently, the evolution of the human MS32 minisatellite DNA locus moved from being a case of single-lineage 'haplotype' evolution [9] to one of'crosstalking' multilineage evolution, following the discovery of frequent interallelic gene conversion events [10]. The precise distribution pattern of each and every mutation at any given frozen moment in time would depend on many factors involving the age of the mutation, the intrachromosomal versus interchromosomal rates of 'crosstalk', and the vagaries of chromosomal drift [11]. The interaction with selection would depend on the variance in the extent to which a variant repeat has spread in each individual in a sexual population. As stated from 1982 onwards [1,11], the maximum variance would occur in the near-absence of interchromosomal turnover, allowing chromosomes to be individually homogenized and selectable as Mendelian 'alleles', an idea re-introduced in the paper under discussion [2]. The finding of chromosome-specific mutations [2] is fascinating, and supports original proposals that homogenization occurs concurrently at different rates and at different levels. The data should not be seen as polarizing the subtle and complex factors driving concerted evolution into two seemingly opposing camps. Rather, they offer the opportunity to dissect the relative contributions of internal and external processes that underlie the evolution of genetic redundancy [3]. References 1. Dover GA: Molecular drive: a cohesive mode of species evolution. Nature 1982, 299:111-117. 2. SchlBtterer C, Tautz D: Chromosomal homogeneity of Drosophila ribosomal DNA arrays suggests intrachromosomal exchanges drive concerted evolution. Curr Biol 1994, 4:777-783. 3. Dover GA: The evolution of genetic redundancy for advanced players. Curr Opin Genet Dev 1993, 3:902-910. 4. Coen ES, Strachan T, Dover GA: The dynamics of concerted evolution of rDNA and histone gene families in the melanogaster species subgroup of Drosophila. J Mol Biol 1982, 158:17-35. 5. Ruiz Linares A, Bowen T, Dover GA: Aspects of non-random turnover involved in the concerted evolution of intergenic spacers within ribosomal DNA of D. melanogaster. I Mol Evol 1984, 39:151-159. 6. Jorgensen AL, Laursen HB, Jones C, Bak AL: Evolutionarily different alphoid repeat DNA on homologous chromosomes in human and chimpanzee. Proc Natl Acad Sci USA 1992, 89:3310-3314. 7. Dover GA: Linkage disequilibrium and molecular drive in the rDNA gene family. Genetics 1989, 122:249-252. 8. Coen ES, Dover GA: Unequal exchanges and the coevolution of X and Y rDNA arrays in D melanogaster. Cell 1983, 33:849-855. 9. Jeffreys AJ, Neumann R, Wilson V: Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism. Cell 1983, 33:849-855. 10. Jeffreys Al, Tamaki K, MacLeod A, Monckton DG, Neil DL, Armour J: Complex gene conversion events in germline mutation at human minisatellites. Nature Genet 1994, 6:136-145. 11. Dover GA, Ruiz-Linares A, Bowen T, Hancock JM: Detection and quantification of concerted evolution and molecular drive. In Methods Enzymol Edited by Zimmer EA, White TJ, Cann RL, Wilson AC. 1993, 244:525-541.
Gabby Dover, Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.
© Current Biology 1994, Vol 4 No 12
1165
1166
Current Biology 1994, Vol 4 No 12 Diethard Tautz and Christian Schltterer reply: We agree that some parts of our paper could be misunderstood as implying that we were proposing a new model for the phenomenon of concerted evolution. This was not our intention. Instead, what we intended to do was to provide experimental data for one of the several mechanisms that are involved in the homogenization process of multigene families. This mechanism is intrachromosomal unequal recombination. From our data, we concluded that this process must be acting relatively fast, and could thus determine the speed of the homogenization process (hence the word 'drive' in the title). The crucial part of our data is the observation that homologous chromosomes can coexist in interbreeding populations that are partially or fully homogenized for different repeat-unit variants. This indicates that there is little recombination between them while they are being
homogenized intrachromosomally. We believe that this observation goes beyond the previous demonstrations of the existence of chromosome-specific variants, and provides new information that needs to be considered when specific models are formulated. On the other hand, we fully agree with Gabby Dover that the molecular drive process as a whole is more complex and requires the full recognition of additional interchromosomal mechanisms to explain concerted evolution in toto. Also, we are aware that some of the conclusions in our paper have previously been proposed, though at the time they were only theoretical possibilities, whereas we have now provided the respective data. Diethard Tautz and Christian Schlotterer, Zoologisches Institut der Universitt Miinchen, Luisenstrasse 14, 80333 Munchen, Germany.