PERSPECTIVES anges associated with polyploidization be a selective advantage when sexual mate ld are probably disadvantageous or deleteri. are scarce. Following this logic, environ in reproductive isolatic oncluded ous., it seems that many K-T polyploids mental upheaval may have been a driving that RGL at duplicated contribute outcompeted their diploid progenitors, force in shaping survivorship probabilities to speciation events that occurred after the probably owing to a higher tolerance of a associated with genome duplication the teleost WGD wider range of environmental conditions, 26. clustered genome duplications in flower No similar studies have been performed Alternatively, in a more 'neutral scenario, ing plants at the K-T boundary provide r plants, but recent experimental work has one could assume that environmental stress tantalizing example. provided evidence that reciprocal silenc leads to an increased incidence of polypro However, owing to uncertainties in the ing or loss of duplicated genes provides an formation: for instance, through the produc- dating of most ancient WGDs, a more gen- important source of epistatic interactions that tion of unreduced, 2n gametes". In this case, eral link between WGDs and major extinc- follow the Bateson-Dobzhansky-Muller model the cataclysmic events that were responsible tions cannot be ascertained. The 2R WGD Bikard et al. show that, in crosses between for the K-T extinction could have increased event in vertebrates may date from 520-550 different accessions of Arabidopsis thaliana, the establishment of polyploid lineages by mya,, close to the mass extinction at loci interact in an epistatic manner to control chance. However, it is unclear whether such the dawn of the Cambrian explosion a recessive embryo lethality. This effect is an increase alone could explain the extent (542 mya-), and the genome duplication explained by divergent evolution occurring to which polyploid plants replaced or in teleosts, which according to the most mong paralogues of an essential duplicated overshadowed their diploid relatives recent estimate happened 226-316 mya", gene when the functional copy is not located may have occurred close to the Permian at the same locus in the different accessions Increased vigour In the adaptive scenario, Triassic(P-T)mass extinction event this results in lowered fitness in the first or eterotic effects and rapid genomic and(250 mya). For other paleopolyploidies- second filial (f, or F, )generations of certain epigenetic changes underlie the ability of for example, in S cerevisiae and the core rosses, which contributes to reproductive polyploids to quickly adapt to more extreme eudicots-there is no indication that they isolation By demonstrating the link between environments. In allopolyploids and autop are linked to mass extinction events gene duplication and genetic incompatibil ploids, increased heterozygosity can lead to ity, the authors provide direct evidence for increased variation in gene expression and Increased species diversity duplicate gene loss as a neutral mechanism in regulatory wiring", which may result in Genome duplications often seem to be that generates post-zygotic isolating barriers increased vigour and faster adaptation to novel accompanied by marked and sudden within existing species or populations onditions=3. Rapid genomic and epigenetic increases in species richness. Although a changes after WGD may similarly lead to link between any specific genome duplica- Subfunctionalization. Other neutral sce increased variation and transgressive traits. tion event and increased species diversit narios might also promote speciation. One Transgressive segregation in polyploids remains correlational rather than causal example would be a case in which both might serve as a pre-adaptation for survival several mechanisms might explain how opies of a gene that has multiple functions in habitats that were not accessible to their gene duplication facilitates the formation(for instance, it is expressed at different diploid parent species. Several studies of novel species. stages in development or in different tissues) have suggested that polyploid plants are are retained in different populations after a more tolerant to a wide of environ- Reciprocal gene loss. Both Werth and duplication event. Should the populations mental conditions compared with thei Windham and Lynch and Force proposed become geographically isolated, the two diploid relatives. Furthermore, many that the loss of different copies of a dupli- duplicate genes in each population could polyploids are invasive 233 and can exploit cated gene in separated populations might subfunctionalize and the orthologues in the habitats that their diploid progenitors can- genetically isolate these populations (FIG. 2). different populations might evolve different not26 34. Polyploid insects also have a wider Divergent resolution of the thousands to tens functions. The resulting F, hybrids from the geographical distribution than their diploid of thousands of genes and regulatory rnAs two populations would develop correctly progenitors, often colonizing northern and that are produced by a genome duplication because each subfunction is performed mountain regions.One of the rare exa event could therefore potentially facilitate by one of the genes from each population. ples of relatively recent polyploidy establish- speciation. However, one-eighth of the F, zygotes will ment in vertebrates is given by the tetraploid Scannell et al. "studied gene loss in lack one of the subfunctions and will die if frog Xenopus laevis, which is a highly three yeast species that have undergone a this function is essentials(FIG. 2b). As a invasive species that colonizes disturbed WGD and showed that, at many loci, dif- result, lineage-specific subfunction parti- and man-made habitats. It is also extremely ferent species lost different members of a tioning could accelerate rates of speciation tolerant to salt, drought, cold and starvation, duplicated pair, so that 4-7% of single-copy and is more disease resistant than its diploid genes compared between any two species Speciation. There seems to be a correlation relative Silurana tropicalis are not orthologues but paralogues. Such a between WGDs in plants and increased In summary, increased phenotypic pattern provides strong evidence for specia- rates of speciation or divergence. First, there variability and heterotic effects have the tion through the reciprocal gene loss(RGl) seems to be a correlation between the old potential to enable polyploids to survive modelb(FIG 2a]. Similar findings have WGDs and the early and fast diversifica environmental conditions that do not favour been reported for duplicated fish genomes, tion of flowering plants$2.53. Second, Soltis their diploid ancestors"(FIG. 1). Polyploidy in which it is estimated that-1, 700(8%) et al. found a strong correlation between is also known to facilitate self-fertilization estral loci of Tetraodon nigroviridi diversification rates and polyploidy follow and the formation of asexually reproduc nd zebrafish underwent RGL". Because ing recent WGDs in many plant lineages. For ing(apomictic)species.,which might RGL at only a few pairs of loci that encode instance, the WGD in the Poaceae lineage URE REVIEWS GENETICS 22009 Macmillan Publishers Limited All rights reservedchanges associated with polyploidization are probably disadvantageous or deleteri￾ous6,11,12, it seems that many K–T polyploids outcompeted their diploid progenitors, probably owing to a higher tolerance of a wider range of environmental conditions25,26. Alternatively, in a more ‘neutral’ scenario, one could assume that environmental stress leads to an increased incidence of polyploid formation: for instance, through the produc￾tion of unreduced, 2n gametes27. In this case, the cataclysmic events that were responsible for the K–T extinction could have increased the establishment of polyploid lineages by chance. However, it is unclear whether such an increase alone could explain the extent to which polyploid plants replaced or overshadowed their diploid relatives. Increased vigour. In the adaptive scenario, heterotic effects and rapid genomic and epigenetic changes underlie the ability of polyploids to quickly adapt to more extreme environments. In allopolyploids and autopoly￾ploids, increased heterozygosity can lead to increased variation in gene expression and in regulatory wiring28, which may result in increased vigour and faster adaptation to novel conditions29,30. rapid genomic and epigenetic changes after WGD may similarly lead to increased variation and transgressive traits28. Transgressive segregation in polyploids might serve as a pre-adaptation for survival in habitats that were not accessible to their diploid parent species22,31. Several studies have suggested that polyploid plants are more tolerant to a wider range of environ￾mental conditions compared with their diploid relatives25,26. Furthermore, many polyploids are invasive32,33 and can exploit habitats that their diploid progenitors can￾not26,34. Polyploid insects also have a wider geographical distribution than their diploid progenitors, often colonizing northern and mountain regions35. one of the rare exam￾ples of relatively recent polyploidy establish￾ment in vertebrates is given by the tetraploid frog Xenopus laevis, which is a highly invasive species that colonizes disturbed and man-made habitats. It is also extremely tolerant to salt, drought, cold and starvation, and is more disease resistant than its diploid relative Silurana tropicalis36,37. In summary, increased phenotypic variability and heterotic effects have the potential to enable polyploids to survive environmental conditions that do not favour their diploid ancestors38 (FIG. 1). Polyploidy is also known to facilitate self-fertilization and the formation of asexually reproduc￾ing (apomictic) species35,39, which might be a selective advantage when sexual mates are scarce. Following this logic, environ￾mental upheaval may have been a driving force in shaping survivorship probabilities associated with genome duplication22; the clustered genome duplications in flower￾ing plants at the K–T boundary provide a tantalizing example. However, owing to uncertainties in the dating of most ancient WGDs, a more gen￾eral link between WGDs and major extinc￾tions cannot be ascertained. The 2r WGD event in vertebrates may date from 520–550 mya19,40, close to the mass extinction at the dawn of the Cambrian explosion (542 mya41–43), and the genome duplication in teleosts, which according to the most recent estimate happened 226–316 mya44, may have occurred close to the Permian– Triassic (P–T) mass extinction event (250 mya). For other paleopolyploidies — for example, in S. cerevisiae and the core eudicots — there is no indication that they are linked to mass extinction events. increased species diversity Genome duplications often seem to be accompanied by marked and sudden increases in species richness. Although a link between any specific genome duplica￾tion event and increased species diversity remains correlational rather than causal, several mechanisms might explain how gene duplication facilitates the formation of novel species. Reciprocal gene loss. Both Werth and Windham45 and lynch and Force46 proposed that the loss of different copies of a dupli￾cated gene in separated populations might genetically isolate these populations (FIG. 2). Divergent resolution of the thousands to tens of thousands of genes and regulatory rnAs that are produced by a genome duplication event could therefore potentially facilitate speciation. Scannell et al.47 studied gene loss in three yeast species that have undergone a WGD and showed that, at many loci, dif￾ferent species lost different members of a duplicated pair, so that 4–7% of single-copy genes compared between any two species are not orthologues but paralogues. Such a pattern provides strong evidence for specia￾tion through the reciprocal gene loss (rGl) model45,46 (FIG. 2a). Similar findings have been reported for duplicated fish genomes, in which it is estimated that ~1,700 (8%) ancestral loci of Tetraodon nigroviridis and zebrafish underwent rGl48. Because rGl at only a few pairs of loci that encode essential genes would be sufficient to result in reproductive isolation, it was concluded that rGl at duplicated loci might contribute to speciation events that occurred after the teleost WGD48. no similar studies have been performed for plants, but recent experimental work has provided evidence that reciprocal silenc￾ing or loss of duplicated genes provides an important source of epistatic interactions that follow the Bateson–Dobzhansky–Muller model. Bikard et al.49 show that, in crosses between different accessions of Arabidopsis thaliana, loci interact in an epistatic manner to control a recessive embryo lethality. This effect is explained by divergent evolution occurring among paralogues of an essential duplicated gene when the functional copy is not located at the same locus in the different accessions; this results in lowered fitness in the first or second filial (F1 or F2 ) generations of certain crosses, which contributes to reproductive isolation. By demonstrating the link between gene duplication and genetic incompatibil￾ity, the authors provide direct evidence for duplicate gene loss as a neutral mechanism that generates post-zygotic isolating barriers within existing species or populations. Subfunctionalization. other neutral sce￾narios might also promote speciation. one example would be a case in which both copies of a gene that has multiple functions (for instance, it is expressed at different stages in development or in different tissues) are retained in different populations after a duplication event. Should the populations become geographically isolated, the two duplicate genes in each population could subfunctionalize46 and the orthologues in the different populations might evolve different functions. The resulting F1 hybrids from the two populations would develop correctly because each subfunction is performed by one of the genes from each population. However, one-eighth of the F2 zygotes will lack one of the subfunctions and will die if this function is essential50,51 (FIG. 2b). As a result, lineage-specific subfunction parti￾tioning could accelerate rates of speciation. Speciation. There seems to be a correlation between WGDs in plants and increased rates of speciation or divergence. First, there seems to be a correlation between the older WGDs and the early and fast diversifica￾tion of flowering plants52,53. Second, Soltis et al.13 found a strong correlation between diversification rates and polyploidy follow￾ing recent WGDs in many plant lineages. For instance, the WGD in the Poaceae lineage Pers P ectives nATurE rEvIEWS | Genetics voluME 10 | oCToBEr 2009 | 727 © 2009 Macmillan Publishers Limited. All rights reserved