M O L E C U L A R B I O L O GY
mitotic cells. NDRs contain gene promoters and are flanked by nucleosomes that contain histone H3 methylated at lysine 4 (H3K4me). H3K4me is implicated primarily in promoter function but is also used to recruit DSBforming proteins during meiosis. In contrast, in most mammals, hotspots show no particular correlation with preexisting chromatin elements. Instead, they contain bindBy Michael Lichten in contrast to the rapid divergence seen in ing sites for positive-regulatory domain zinc mammals, hotspot patterns in budding yeast finger protein 9 (PRDM9), a meiotic protein exual reproduction involves the proshow a high degree of conservation. with a highly variable zinc finger array that duction of haploid gametes from dipSinghal, Leffler, and colleagues derived recognizes specific sequences and that cataloid cells through a series of genome meiotic recombination maps from singlelyzes the formation of H3K4me in its vicinity. divisions, called meiosis. Accurate meinucleotide polymorphism distributions in Thus, yeast hotspots are likely maintained otic chromosome segregation requires small populations of two Australian birds, because their constituent elements perform homologous recombination, initiated the zebra finch and long-tailed finch, again other important functions. PRDM9-desigby programmed DNA double-strand breaks with sequence divergence similar to that nated hotspots in mammals are under no (DSBs). DSBs are focused at sites, called between humans and chimpanzees. As with such constraints, and thus can undergo rapid hotspots, where recombination evolution in which hotspot evappreferentially occurs (1). Because oration is balanced by the rapid DSB repair by recombination inevolution of new binding specivolves copying information from ficity in PRDM9 (7). The finding an unbroken chromosome, one that bird hotspots are also conprevailing view is that, over time, served suggests that birds, like DSB hotspots should be replaced yeast, designate hotspots using PRDM9 by “cold” sequence variants that genomic elements that are under reduce DSBs at the same site (2). functional selection. Consistent with this paradigm, The existence of at least two NDR hotspot patterns in mice and pridifferent modes of hotspot desmates display high divergence ignation, with accompanying DNA sequence Constrained functional element between species and even indidifferences in evolutionary staRapid evolution Evolutionary stability viduals (3). This view is now chalbility, raises a question: If birds Different mechanisms, different outcomes. In mammals, meiotic recombination lenged by two research articles and yeast do it one way, and most hotspots contain sequences where PRDM9 binds and forms chromatin marks (stars) in this issue, by Lam and Keeney mammals do it another way, what that promote double-strand breaks. Both PRDM9 and its target sequences evolve (page 932) and Singhal et al. (page about other eukaryotes? In this rapidly. In yeast, birds, and other eukaryotes, breaks form at preexisting genomic 928), that characterize recombiregard, it is worth noting that elements with recombination-independent functions that ensure evolutionary nation hotspot patterns in species hotspots also appear to be sestability—in this example, a nucleosome-depleted region (NDR) with a gene promoter of budding yeast (4) and birds (5), quence-independent, and are asthat already contains break-promoting chromatin marks. respectively. Both papers docusociated with functional genomic ment remarkable hotspot pattern elements, in plants (8); in dogs, stability over evolutionary time, suggesting yeast, a large fraction of hotspots in the two which naturally lack a functional PRDM9 (9); that the picture in mammals may be the exfinches (>70%) colocalized. Using elevated and even in Prdm9–/– mutant mice (10). These ception rather than the rule. GC content, a hallmark of GC-biased gene observations, together with the exciting findLam and Keeney compared genome-wide conversion (6), as a signal for hotspots, the ings of Lam and Keeney and of Singhal et meiotic DSB maps in Saccharomyces cereviauthors examined the ensemble of hotspots al., raise the intriguing possibility that the siae strains with roughly the same sequence shared between the two finches in three yeast and bird paradigm for hotspot designadivergence—a measure of separation in evoother species: the Australian double-barred tion may be the primordial one, and that the lutionary time—as humans and chimpanzees, finch, the medium ground finch from the mammalian mechanism of sequence-based and in four Saccharomyces species, including Galapagos, and the Old World collared flydesignation may be a relative latecomer to a pair (S. cerevisiae and S. kudriavzevii) with catcher. Despite their broad geographical the game. ■ roughly the same sequence divergence as and evolutionary separation, all five species REFERENCES mammals and birds. Hotspot patterns among showed elevated GC content at these loci, 1. B. de Massy, Annu. Rev. Genet. 47, 563 (2013). S. cerevisiae strains showed almost complete consistent with the retention of a substantial 2. A. Nicolas et al., Nature 338, 35 (1989). overlap, and even the distantly related S. ceresubset of hotspots. Thus, in birds as in yeast, 3. F. Baudat, Y. Imai, B. de Massy, Nat. Rev. Genet. 14, 794 visiae and S. kudriavzevii showed a greater but unlike in mammals, meiotic recombina(2013). 4. I. Lam, S. Keeney, Science 350, 932 (2015). than 80% overlap in hotspot locations. Even tion patterns appear to be highly conserved 5. S. Singhal et al., Science 350, 928 (2015). more remarkably, Lam and Keeney found over broad swaths of evolutionary time. 6. M. T. Webster, L. D. Hurst, Trends Genet. 28, 101 (2012). that different species often displayed similar The cause of this difference may be found 7. Y. Lesecque et al., PLOS Genet. 10, e1004790 (2014). fine-structure break distributions and DSB in the different ways that yeast and mam8. K. Choi et al., Nat. Genet. 45, 1327 (2013). 9. A. Auton et al., PLOS Genet. 9, e1003984 (2013). frequencies at individual hotspots. Thus, mals designate DSB hotspots (1). Yeast 10. K. Brick et al., Nature 485, 642 (2012). hotspots do not share specific sequences, but instead are located in the nucleosomeNational Cancer Institute, Bethesda, MD 20892, USA. E-mail: [email protected] depleted regions (NDRs) already present in 10.1126/science.aad5404
Putting the breaks on meiosis
ILLUSTRATION: P. HUEY/SCIENCE
S
SCIENCE sciencemag.org
20 NOVEMBER 2015 • VOL 350 ISSUE 6263
Published by AAAS
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Downloaded from www.sciencemag.org on November 19, 2015
Yeast and birds reveal remarkable evolutionary stability in recombination patterns
Putting the breaks on meiosis Michael Lichten Science 350, 913 (2015); DOI: 10.1126/science.aad5404
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Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
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mitotic cells. NDRs contain gene promoters and are flanked by nucleosomes that contain histone H3 methylated at lysine 4 (H3K4me). H3K4me is implicated primarily in promoter function but is also used to recruit DSBforming proteins during meiosis. In contrast, in most mammals, hotspots show no particular correlation with preexisting chromatin elements. Instead, they contain bindBy Michael Lichten in contrast to the rapid divergence seen in ing sites for positive-regulatory domain zinc mammals, hotspot patterns in budding yeast finger protein 9 (PRDM9), a meiotic protein exual reproduction involves the proshow a high degree of conservation. with a highly variable zinc finger array that duction of haploid gametes from dipSinghal, Leffler, and colleagues derived recognizes specific sequences and that cataloid cells through a series of genome meiotic recombination maps from singlelyzes the formation of H3K4me in its vicinity. divisions, called meiosis. Accurate meinucleotide polymorphism distributions in Thus, yeast hotspots are likely maintained otic chromosome segregation requires small populations of two Australian birds, because their constituent elements perform homologous recombination, initiated the zebra finch and long-tailed finch, again other important functions. PRDM9-desigby programmed DNA double-strand breaks with sequence divergence similar to that nated hotspots in mammals are under no (DSBs). DSBs are focused at sites, called between humans and chimpanzees. As with such constraints, and thus can undergo rapid hotspots, where recombination evolution in which hotspot evappreferentially occurs (1). Because oration is balanced by the rapid DSB repair by recombination inevolution of new binding specivolves copying information from ficity in PRDM9 (7). The finding an unbroken chromosome, one that bird hotspots are also conprevailing view is that, over time, served suggests that birds, like DSB hotspots should be replaced yeast, designate hotspots using PRDM9 by “cold” sequence variants that genomic elements that are under reduce DSBs at the same site (2). functional selection. Consistent with this paradigm, The existence of at least two NDR hotspot patterns in mice and pridifferent modes of hotspot desmates display high divergence ignation, with accompanying DNA sequence Constrained functional element between species and even indidifferences in evolutionary staRapid evolution Evolutionary stability viduals (3). This view is now chalbility, raises a question: If birds Different mechanisms, different outcomes. In mammals, meiotic recombination lenged by two research articles and yeast do it one way, and most hotspots contain sequences where PRDM9 binds and forms chromatin marks (stars) in this issue, by Lam and Keeney mammals do it another way, what that promote double-strand breaks. Both PRDM9 and its target sequences evolve (page 932) and Singhal et al. (page about other eukaryotes? In this rapidly. In yeast, birds, and other eukaryotes, breaks form at preexisting genomic 928), that characterize recombiregard, it is worth noting that elements with recombination-independent functions that ensure evolutionary nation hotspot patterns in species hotspots also appear to be sestability—in this example, a nucleosome-depleted region (NDR) with a gene promoter of budding yeast (4) and birds (5), quence-independent, and are asthat already contains break-promoting chromatin marks. respectively. Both papers docusociated with functional genomic ment remarkable hotspot pattern elements, in plants (8); in dogs, stability over evolutionary time, suggesting yeast, a large fraction of hotspots in the two which naturally lack a functional PRDM9 (9); that the picture in mammals may be the exfinches (>70%) colocalized. Using elevated and even in Prdm9–/– mutant mice (10). These ception rather than the rule. GC content, a hallmark of GC-biased gene observations, together with the exciting findLam and Keeney compared genome-wide conversion (6), as a signal for hotspots, the ings of Lam and Keeney and of Singhal et meiotic DSB maps in Saccharomyces cereviauthors examined the ensemble of hotspots al., raise the intriguing possibility that the siae strains with roughly the same sequence shared between the two finches in three yeast and bird paradigm for hotspot designadivergence—a measure of separation in evoother species: the Australian double-barred tion may be the primordial one, and that the lutionary time—as humans and chimpanzees, finch, the medium ground finch from the mammalian mechanism of sequence-based and in four Saccharomyces species, including Galapagos, and the Old World collared flydesignation may be a relative latecomer to a pair (S. cerevisiae and S. kudriavzevii) with catcher. Despite their broad geographical the game. ■ roughly the same sequence divergence as and evolutionary separation, all five species REFERENCES mammals and birds. Hotspot patterns among showed elevated GC content at these loci, 1. B. de Massy, Annu. Rev. Genet. 47, 563 (2013). S. cerevisiae strains showed almost complete consistent with the retention of a substantial 2. A. Nicolas et al., Nature 338, 35 (1989). overlap, and even the distantly related S. ceresubset of hotspots. Thus, in birds as in yeast, 3. F. Baudat, Y. Imai, B. de Massy, Nat. Rev. Genet. 14, 794 visiae and S. kudriavzevii showed a greater but unlike in mammals, meiotic recombina(2013). 4. I. Lam, S. Keeney, Science 350, 932 (2015). than 80% overlap in hotspot locations. Even tion patterns appear to be highly conserved 5. S. Singhal et al., Science 350, 928 (2015). more remarkably, Lam and Keeney found over broad swaths of evolutionary time. 6. M. T. Webster, L. D. Hurst, Trends Genet. 28, 101 (2012). that different species often displayed similar The cause of this difference may be found 7. Y. Lesecque et al., PLOS Genet. 10, e1004790 (2014). fine-structure break distributions and DSB in the different ways that yeast and mam8. K. Choi et al., Nat. Genet. 45, 1327 (2013). 9. A. Auton et al., PLOS Genet. 9, e1003984 (2013). frequencies at individual hotspots. Thus, mals designate DSB hotspots (1). Yeast 10. K. Brick et al., Nature 485, 642 (2012). hotspots do not share specific sequences, but instead are located in the nucleosomeNational Cancer Institute, Bethesda, MD 20892, USA. E-mail: [email protected] depleted regions (NDRs) already present in 10.1126/science.aad5404
Putting the breaks on meiosis
ILLUSTRATION: P. HUEY/SCIENCE
S
SCIENCE sciencemag.org
20 NOVEMBER 2015 • VOL 350 ISSUE 6263
Published by AAAS
913
Downloaded from www.sciencemag.org on November 19, 2015
Yeast and birds reveal remarkable evolutionary stability in recombination patterns
Putting the breaks on meiosis Michael Lichten Science 350, 913 (2015); DOI: 10.1126/science.aad5404
This copy is for your personal, non-commercial use only.
If you wish to distribute this article to others, you can order high-quality copies for your colleagues, clients, or customers by clicking here.
The following resources related to this article are available online at www.sciencemag.org (this information is current as of November 19, 2015 ): Updated information and services, including high-resolution figures, can be found in the online version of this article at: http://www.sciencemag.org/content/350/6263/913.full.html A list of selected additional articles on the Science Web sites related to this article can be found at: http://www.sciencemag.org/content/350/6263/913.full.html#related This article cites 10 articles, 2 of which can be accessed free: http://www.sciencemag.org/content/350/6263/913.full.html#ref-list-1 This article appears in the following subject collections: Molecular Biology http://www.sciencemag.org/cgi/collection/molec_biol
Science (print ISSN 0036-8075; online ISSN 1095-9203) is published weekly, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. Copyright 2015 by the American Association for the Advancement of Science; all rights reserved. The title Science is a registered trademark of AAAS.
Downloaded from www.sciencemag.org on November 19, 2015
Permission to republish or repurpose articles or portions of articles can be obtained by following the guidelines here.
