PERSPECTIVES shows little evidence of du tionalization or neofunctionalization s-60 Any theory that attempts to link wGD to species diversity should take into account the fact that radiations are not always pre- Genome duplication t ceded by genome duplications. Invertebrates and vertebrates have diversified at similar ates, despite the fact that the vertebrates underwent two rounds of genome duplication and the invertebrates none Evolutionary innovations In the longer run, polyploidy may pave the way for evolutionary innovations or elabora- tions of existing morphological structures that allow exploration of fundamentally Geographic different regions of phenotype space ene loss solaria Subfunctionalization Genome duplication favours gene retention One of the prerequisites for developing more complex systems is an increase in the CDCD DO number of gene regulators. Intriguingly, duplications are the preferred way to ccomplish such an increase. Transcriptional Population1\ POpulation 2 lation\ y and developmental regulators and signal transducers have been preferentially retained in duplicate after all genome duplications in bidopsis thaliana63-65, after the IR and 21 WGDs in vertebrates 9,66 after 3R in fish, 67, and after the WGD in yeast.69. Mo these regulatory gene classes cannot be cations, which accentuates the importane of genome duplications in expanding the regulatory gene repertoire. Maere et al. as estimated that more than 90% of the increase in regulatory genes in the Arabidopsis lineage in the last-150 million years caused by genome duplications. Both under-retention of regulators after gene duplications and their over-retention after genome duplications can be explained by dosage balance effects.. Freeling and Thomas"and Freeling"argue that, after 個DD( modules are inherently retained in duplicate Figure 2I Reciprocal gene loss or subfunctionalization facilitates speciation. Red bands on after which they can adaptively evolve novel tion event. a After diploidization, the duplicated gene is present on two different chromosomes. After geographic isolation, both populations have lost one of the duplicates on different chromo- functions and might ultimately cause an somes. If individuals from isolated populations mate. their hybrid progeny would be heterozygous. increase in morphological complexity possessing a functional allele at each locus of the duplicated gene. However, one-sixteenth The study of individual gene families also (approximately 6%)of crosses between the first filial( F, individuals produce second filial(F)indi- points to the importance of genome duplica- viduals that have null alleles at both loci in question(dark grey square)and therefore lack viability tions in expanding the regulatory gene rep- and/or fertility. Others might receive one allele(light grey squares), which might reduce functional- ertoire of an organism. In plants, important ity when a gene is haploinsufficient, or might receive three or four functional alleles (mid-grey developmental regulators, such as the AUX/ juares), which might have a negative dosage effect. All these outcomes might lead to post-mating certain MADS-box transcription factor sub. cated genes in the different populations have subfunctionalized (orange and yellow bands on families?,76, seem to have expanded mainly but one-sixteenth of the F, generation will be homozygous for alleles lacking one essential sub through genome duplications In vertebrates, function, and another one-sixteenth will be homozygous for alleles lacking the other essential IR and 2R are thought to be responsible for subfunction (dark grey squares), thus reducing the fitness of hybrids. Other F, individuals might, the expansion of the number of homeobox as in a, show reduced fitness caused by dosage or haploinsufficiency effects. URE REVIEWS GENETICS VOLUME 10 lOCTOBER 20091729 22009 Macmillan Publishers Limited All rights reservedNature Reviews | Genetics F2 F1 F1 a Geographic isolation Geographic isolation Gene loss Subfunctionalization Population 1 Population 2 Population 1 Population 2 Diploid Polyploid Paleopolyploid b Genome duplication Genome duplication Diploidization Diploidization Figure 2 | Reciprocal gene loss or subfunctionalization facilitates speciation. red bands on chromosomes represent a locus that is duplicated (along with all other loci) during a tetraploidiza￾tion event. a | After diploidization, the duplicated gene is present on two different chromosomes. After geographic isolation, both populations have lost one of the duplicates on different chromo￾somes. if individuals from isolated populations mate, their ‘hybrid’ progeny would be heterozygous, possessing a functional allele at each locus of the duplicated gene. However, one-sixteenth (approximately 6%) of crosses between the first filial (F1 ) individuals produce second filial (F2 ) indi￾viduals that have null alleles at both loci in question (dark grey square) and therefore lack viability and/or fertility. Others might receive one allele (light grey squares), which might reduce functional￾ity when a gene is haploinsufficient, or might receive three or four functional alleles (mid-grey squares), which might have a negative dosage effect. All these outcomes might lead to post-mating reproductive isolation46. b | in this scenario, after diploidization and geographic isolation, the dupli￾cated genes in the different populations have subfunctionalized (orange and yellow bands on chromosomes). Hybrids between the two populations should in general develop normally, but one-sixteenth of the F2 generation will be homozygous for alleles lacking one essential sub￾function, and another one-sixteenth will be homozygous for alleles lacking the other essential subfunction (dark grey squares), thus reducing the fitness of hybrids. Other F2 individuals might, as in a, show reduced fitness caused by dosage or haploinsufficiency effects. shows little evidence of duplicate subfunc￾tionalization or neofunctionalization58–60. Any theory that attempts to link WGD to species diversity should take into account the fact that radiations are not always pre￾ceded by genome duplications. Invertebrates and vertebrates have diversified at similar rates61, despite the fact that the vertebrates underwent two rounds of genome duplication and the invertebrates none. Evolutionary innovations In the longer run, polyploidy may pave the way for evolutionary innovations or elabora￾tions of existing morphological structures that allow exploration of fundamentally different regions of phenotype space. Genome duplication favours gene retention. one of the prerequisites for developing more complex systems is an increase in the number of gene regulators62. Intriguingly, genome duplications are the preferred way to accomplish such an increase. Transcriptional and developmental regulators and signal transducers have been preferentially retained in duplicate after all genome duplications in Arabidopsis thaliana63–65, after the 1r and 2r WGDs in vertebrates19,66, after 3r in fish66,67 , and after the WGD in yeast68,69. Moreover, these regulatory gene classes cannot be expanded easily through single-gene dupli￾cations, which accentuates the importance of genome duplications in expanding the regulatory gene repertoire. Maere et al.63 estimated that more than 90% of the increase in regulatory genes in the Arabidopsis lineage in the last ∼150 million years is caused by genome duplications. Both the under-retention of regulators after single￾gene duplications and their over-retention after genome duplications can be explained by dosage balance effects70,71. Freeling and Thomas72 and Freeling73 argue that, after genome duplication, entire functional modules are inherently retained in duplicate through non-adaptive dosage balance effects, after which they can adaptively evolve novel functions and might ultimately cause an increase in morphological complexity. The study of individual gene families also points to the importance of genome duplica￾tions in expanding the regulatory gene rep￾ertoire of an organism. In plants, important developmental regulators, such as the AuX/ IAA family of auxin response regulators74 and certain MADS-box transcription factor sub￾families75,76, seem to have expanded mainly through genome duplications. In vertebrates, 1r and 2r are thought to be responsible for the expansion of the number of homeobox Pers P ectives nATurE rEvIEWS | Genetics voluME 10 | oCToBEr 2009 | 729 © 2009 Macmillan Publishers Limited. All rights reserved