Leading Edge Review The Evolutionary Consequences of Polyploidy Sarah P. Otto1,* 1Department of Zoology, University of British Columbia, 6270 University Boulevard, Vancouver BC V6T 1Z4 Canada *Correspondence: [email protected] DOI 10.1016/j.cell.2007.10.022 Polyploidization, the addition of a complete set of chromosomes to the genome, represents one of the most dramatic mutations known to occur. Nevertheless, polyploidy is well toler- ated in many groups of eukaryotes. Indeed, the majority of flowering plants and vertebrates have descended from polyploid ancestors. This Review examines the short-term effects of polyploidization on cell size, body size, genomic stability, and gene expression and the long-term effects on rates of evolution. One of the most striking features of genome structure homology but are sufficiently distinct due to their sepa- is its lability. From small-scale rearrangements to large- rate origins, these pairs of chromosomes are referred scale changes in size, genome comparisons among to as homeologs (see Figure 1). Polyploidy is especially species reveal that variation is commonplace. Even over prevalent among hybrid taxa, an association thought the short time course of laboratory experiments, chro- to be driven by problems with meiotic pairing in diploid mosomal rearrangements, duplications/deletions of hybrids, which are solved if each homeologous chromo- chromosome segments, and shifts in ploidy have been some has its own pairing partner. Additionally, diploid observed and have contributed to adaptation (Dunham hybrids form unreduced gametes (which have the same et al., 2002; Gerstein et al., 2006; Riehle et al., 2001). number of chromosomes as somatic cells) at unusually Changes in genome structure typically have immediate high rates (Ramsey and Schemske, 2002), increasing the effects on the phenotype and fitness of an individual. rate of formation of polyploids from hybrid lineages. By Beyond these immediate effects, changes in genome combining traits from two parental species and ensuring structure might allow evolutionary transitions that were fair segregation of these traits, allopolyploids potentially previously impossible. For example, by introducing an benefit from “hybrid vigor” (where hybrids have charac- additional complement of chromosomes, polyploidiza- teristics that make them superior to both parental spe- tion might release gene duplicates from the constraints cies) and an altered ecological niche without the prob- of having to perform all of the functions of a gene (pleiot- lems associated with segregation and breakdown at the ropy), providing extra “degrees of freedom” upon which F2 generation that occurs among diploid hybrids. selection can act to favor new functions. Polyploidiza- Chromosomes that have previously diverged and been tion can also stimulate further structural changes in the brought together by hybridization typically segregate genome, providing polyploid lineages with genomic vari- as bivalents (Figure 1C; Ramsey and Schemske, 2002). ation not available to diploid organisms. Indeed, it has Genomic analyses have begun to unravel the genes been proposed that tetraploidy may be an intermediate responsible for bivalent pairing, ensuring that homologs stage in some cancers, facilitating a cascade of struc- rather than homeologs pair during meiosis (e.g., at the tural changes that disrupt normal controls to cell growth Ph1 locus in polyploid wheat; Griffiths et al., 2006). In (Storchova and Pellman, 2004). Here, I discuss the evo- contrast, autopolyploids more often exhibit multivalent lutionary impact of polyploidization, beginning with the pairing than allopolyploids (Figure 1B), ~3.5 times more prevalence of polyploidy, and then I explore the longer- so in plants (Ramsey and Schemske, 2002). In most term consequences of polyploidy on the rate and nature cases, descendants of a polyploidization event in the of evolutionary transitions. distant past (“paleopolyploids”) exhibit bivalent pairing of chromosomes and disomic inheritance (as if diploid). Incidence of Polyploidization This observation has traditionally led to the conclusion Polyploidization is the increase in genome size caused by that autopolyploids are ephemeral whereas allopoly- the inheritance of an additional set (or sets) of chromo- ploids give rise to the majority of long-lasting lineages somes (Figure 1). The duplicated sets of chromosomes (Grant, 1971; Stebbins, 1950). Bivalent pairing, however, may originate from the same or a closely related indi- can occur and is even more prevalent (63.7%) than mul- vidual (“autopolyploid”) or from the hybridization of two tivalent pairing (28.8%) among newly formed autotetra- different species (“allopolyploidy”). When polyploidiza- ploid plants (Ramsey and Schemske, 2002). Although tion involves duplicated sets of chromosomes that share bivalent pairing is initially nonpreferential in autopo- 452 Cell 131, November 2, 2007 ©2007 Elsevier Inc. lyploids, leading to tetrasomic gene duplicates is very long inheritance (Figure 1), segregating (over a million generations; polymorphisms, especially rear- Lynch, 2007). Conversely, rangements and indels (insertions aneuploids often have low and deletions), may increase pair- fitness and, in mammals, ing fidelity over time ultimately rarely survive to reproduce. yielding disomic inheritance. Indeed, it is exceedingly rare Increased pairing fidelity may for a homologous chromo- also stem from genetic changes, some pair to be lost or dupli- such as at the Ph1 locus in wheat cated among all members of (Griffiths et al., 2006). Thus, one a population. In mammals cannot assume that a paleopoly- and birds, ploidy changes ploid is necessarily allopolyploid are also typically fatal, with solely because it exhibits disomic polyploids dying early during inheritance; additional evidence development. Interestingly, is needed, such as phylogenetic polyploidy is lethal regard- evidence that different genomic less of the sexual phenotype regions are more closely related of the embryo (e.g., triploid to different parental species. XXX humans, which develop Autopolyploids are also less fre- as females, die, as do triploid quently recognized as distinct ZZZ chickens, which develop species than allopolyploids, even as males), and polyploidy when they are reproductively iso- causes much more severe lated and morphologically differ- defects than trisomy involv- entiated from their diploid parents ing the sex chromosomes (Soltis et al., 2007). Thus, recent (diploids with an extra X or Y papers have argued that autopo- chromosome). Thus, in mam- lyploidy may contribute more to Figure 1. Polyploidy Terminology mals and birds, evidence evolution and species diversifi- Two nonhomologous chromosomes are shown (long and suggests that a general dis- short), with each X-shaped chromosome representing a cation than traditionally thought pair of sister chromatids joined at the centromere. In dip- ruption of development—not (Soltis et al., 2007). loids (A), each chromosome consists of a homologous problems restricted to sex Mutations affecting ploidy pair, with one chromosome inherited from the mother and determination—is the root one from the father. In tetraploids (B and C), the chromo- occur relatively frequently in both somes are further doubled. When the duplicated chromo- cause of the failure of poly- plants and animals. Plants pro- somes are very similar to one another, they might align ploids to persist. Specific duce unreduced gametes, a com- randomly in pairs during meiosis (bivalent pairing; not developmental problems in mon route to polyploidization, shown) or all align together (multivalent pairing; B). In ei- human polyploid aborted ther case, gametes may inherit any combination of paren- at an average rate of ~0.5% per tal chromosomes (multisomic inheritance), and mutations fetuses have been attributed gamete (Ramsey and Schemske, that arise on one chromosome can spread to all other to abnormal imprinting and 1998). Both unreduced gametes copies, inhibiting their divergence. When polyploidization placental development (see involves chromosomes that are sufficiently distinct (that is, and polyspermy contribute to the “homeologs”; differentiated by blue and purple), the more references in Otto and Whit- production of polyploid animals. similar pair of chromosomes tend to align together to the ton, 2000). Among chicken embryos, 0.9% exclusion of the other pair (C). With strict bivalent pairing, In many taxa besides the homeologs behave as distinct chromosomes and seg- are triploid or tetraploid (Bloom, regate independently (disomic inheritance), allowing their mammals and birds, how- 1972), and among spontane- divergence. Newly formed autopolyploids typically exhibit ever, polyploidy is surpris- ous human abortions, 5.3% are multisomic inheritance, whereas newly formed allopoly- ingly well tolerated. Poly- ploids exhibit a variety of patterns of inheritance, depend- triploid or tetraploid (Creasy et ing on the cross (Ramsey and Schemske, 2002). ploid lineages often persist al., 1976). Placing these rates in in plants, which is imme- context, gene duplication events diately apparent from the are much rarer, with a roughly 10−8 chance of occurring excess of even over odd chromosome numbers (Figure per gene copy per generation (Lynch, 2007). Conversely, 2). Because doubling a number always generates an aneuploidy, the gain or loss of a single copy of a chromo- even number, this excess of even chromosome numbers some, can be much more frequent;