NEWS AND VIEWS 822 VOLUME 42 | NUMBER 10 | OCTOBER 2010 | NATURE GENETICS human hotspots, other gene products are likely to play hotspot-specific roles. Berg et al. 6 confirm that PRDM9 plays a key role in both allelic recombination and certain forms of genome instability and demonstrate the remarkable effect that variation in one gene can have on specific recombination and mutation events. Furthermore, they raise the question of which, if any, recurrent genomic mutations are activated by individuals lacking the common PRDM9 allele and whether, because there are strong population differences in PRDM9 alleles, NAHR disorders may also have large differ- ences in frequency between populations. Future studies are needed to search for the molecular partners of PRDM9 in recruiting recombina- tion and to characterize which of these partners play general versus hotspot-specific roles. COMPETING FINANCIAL INTERESTS The authors declare no competing financial interests. 1. Ptak, S.E. et al. Nat. 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Jeffreys, A.J. & Neumann, R. Hum. Mol. Genet. 14, 2277–2287 (2005). inactivity for almost all non-A PRDM9 alleles. More likely, PRDM9 may be capable of binding highly degenerate copies of the motif, and it is possible that a favorable flanking sequence 7 strengthens binding to highly degen- erate motifs. Consistent with this idea, sequences containing three mismatches to the eight non- degenerate bases in the 13-bp motif occur near the center of each of the five non-motif hotspots examined by Berg et al. 6 Another possibility is that PRDM9 does bind in a sequence-specific manner but also exerts H3K4me3 activity in cis at some distance from the binding location. Although PRDM9 is an important player in recombination, additional factors influ- ence binding and hotspot activity. Modifiers of recombination rate have been identified at the genome-wide level 12,13 , and there are differences between recombination rates in males and females at megabase scales 14 . Within several hotspots, specific SNPs influencing recombination activity have been identified 15 , and these SNPs often occur in sequences lack- ing the 13-bp motif. Further, previous statisti- cal analysis 7 has identified multiple additional motifs enriched in recombination hotspots but which bear no homology to the predicted PRDM9 binding sequence. For example, one of the motif-containing hotspots studied by Berg et al. 6 is centered within a THE1B retrotrans- poson. On this specific repeat background, the presence of an 8-bp motif, 129 bp upstream from the 13-bp motif and therefore outside the region likely bound by PRDM9, leads to a twofold increase in the average recombination rate 11 . The apparent background specificity of this motif and others suggests that although PRDM9 binding is a shared feature across to the motif. The results of Berg et al. imply that PRDM9 is involved in a much higher fraction of hotspots than the 40% previously estimated to be activated by the motif, and that PRDM9 may be involved in all hotspots. Berg et al. further found that these hotspots are primarily activated by the common reference PRDM9 allele (referred to as allele A). However, in an additional hotspot cluster, one hotspot was activated more strongly by a non-A allele and the other hotspot was activated only by non-A alleles, with subtle amino acid changes within the array strongly altering hotspot activity. The connections between recombination, minisatellite and NAHR rearrangement events suggest that PRDM9 variation is likely to influence rearrangement frequencies, at least where the 13-bp motif is present. Berg et al. 6 directly tested this prediction, finding that for three hypervariable minisatellites where the repeated element contains a close match to the hotspot motif 7 , and for a recurrent NAHR rearrangement where there is also a crossover hotspot likely driven by the hotspot motif 7,10 , variation in PRDM9 has a profound effect on the rate of mutation. In contrast, at a recurrent translocation site where there was no previous evidence for the involvement of recombina- tion or the hotspot motif, PRDM9 variation had no influence on the mutation rate. Motifs and modifiers Berg et al. 6 demonstrate that in some cases, PRDM9 may define hotspot location without binding to the known 13-bp hotspot motif. This may suggest that different zinc fingers are required for binding to different hotspots 11 . However, this seems unlikely given the consistent Harvesting the apple genome James Giovannoni The genome sequence of the domesticated apple has been assembled and compared to previously sequenced plant genomes. The genetic sequence of the 17 apple chromosomes shows evidence of a recent genome duplication that may have spawned the additional gene family members needed for the evolution and development of the unique fruit structure of the apple termed the pome. James Giovannoni is at the United States Department of Agriculture, Agricultural Research Service and the Boyce Thompson Institute for Plant Research, Cornell University, Ithaca, New York, USA. e-mail: jjg3@cornell.edu On page 833 of this issue, an international consortium of plant scientists led by the Istituto Agrario di San Michele all’Adige (IASMA) Research and Innovation Center in Trento, Italy report the genome sequence of the cultivated apple (Malus × domestica) 1 . Apples are among the most widely grown and consumed fruits in temperate regions of the world. This is in part due to years of extensive worldwide breeding and selec- tion resulting in a treasure trove of apple colors, flavors and textures with broad ver- satility for the creation of numerous fresh and processed foods. Equally important to the apple’s prominence in the marketplace (though less appreciated) is the fact that its unique fruit structure, termed a pome, has proven amenable to long-term controlled- atmosphere storage, facilitating year-round availability of high quality fruit from a crop © 2010 Nature America, Inc. All rights reserved.