scholarly journals Evolution of the Yeast Recombination Landscape

2018 ◽  
Vol 36 (2) ◽  
pp. 412-422 ◽  
Author(s):  
Haoxuan Liu ◽  
Calum J Maclean ◽  
Jianzhi Zhang
Keyword(s):  
Recombination Rate ◽  
Yeast Species ◽  
Evolutionary Conservation ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Crossover Interference ◽  
Recombination Hotspots ◽  
Genomic Landscape ◽  
Evolutionarily Conserved ◽  
Cold Spots

Abstract Meiotic recombination comprises crossovers and noncrossovers. Recombination, crossover in particular, shuffles mutations and impacts both the level of genetic polymorphism and the speed of adaptation. In many species, the recombination rate varies across the genome with hot and cold spots. The hotspot paradox hypothesis asserts that recombination hotspots are evolutionarily unstable due to self-destruction. However, the genomic landscape of double-strand breaks (DSBs), which initiate recombination, is evolutionarily conserved among divergent yeast species, casting doubt on the hotspot paradox hypothesis. Nonetheless, because only a subset of DSBs are associated with crossovers, the evolutionary conservation of the crossover landscape could differ from that of DSBs. Here, we investigate this possibility by generating a high-resolution recombination map of the budding yeast Saccharomyces paradoxus through whole-genome sequencing of 50 meiotic tetrads and by comparing this recombination map with that of S. cerevisiae. We observe a 40% lower recombination rate in S. paradoxus than in S. cerevisiae. Compared with the DSB landscape, the crossover landscape is even more conserved. Further analyses indicate that the elevated conservation of the crossover landscape is explained by a near-subtelomeric crossover preference in both yeasts, which we find to be attributable at least in part to crossover interference. We conclude that the yeast crossover landscape is highly conserved and that the evolutionary conservation of this landscape can differ from that of the DSB landscape.

scholarly journals Lessons from the meiotic recombination landscape of the ZMM deficient budding yeast Lachancea waltii

2021 ◽  
Author(s):  
Fabien Dutreux ◽  
Abhishek Dutta ◽  
Emilien Peltier ◽  
Sabrina Bibi-Triki ◽  
Anne Friedrich ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Budding Yeast ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Yeast Saccharomyces Cerevisiae ◽  
Strand Breaks ◽  
Crossover Interference ◽  
Recombination Hotspots ◽  
Elevated Frequency ◽  
Underlying Mechanisms

Meiotic recombination has been deeply characterized in a few model species only, notably in the budding yeast Saccharomyces cerevisiae. Interestingly, most members of the ZMM pathway that implements meiotic crossover interference in S. cerevisiae have been lost in Lachancea yeast species after the divergence of Lachancea kluyveri from the rest of the clade. This suggests major differences in the control of crossover distribution. After investigating meiosis in L. kluyveri, we determined the meiotic recombination landscape of Lachancea waltii and identified several characteristics that should help understand better the underlying mechanisms. Such characteristics include systematic regions of loss of heterozygosity (LOH) in L. waltii hybrids, compatible with dysregulated Spo11-mediated DNA double strand breaks (DSB) independently of meiosis. They include a higher recombination rate in L. waltii than in L. kluyveri despite the lack of multiple ZMM pro-crossover factors. L. waltii exhibits an elevated frequency of zero-crossover bivalents as L. kluyveri but opposite to S. cerevisiae. L. waltii gene conversion tracts lengths are comparable to those observed in S. cerevisiae and shorter than in L. kluyveri despite the lack of Mlh2, a factor limiting conversion tracts size in S. cerevisiae. L. waltii recombination hotspots are not shared with either S. cerevisiae or L. kluyveri, showing that meiotic recombination hotspots can evolve at a rather limited evolutionary scale within budding yeasts. Finally, in line with the loss of several ZMM genes, we found only residual crossover interference in L. waltii likely coming from the modest interference existing between recombination precursors.

scholarly journals Crossover Interference in Arabidopsis

Genetics ◽  
2002 ◽  
Vol 160 (4) ◽  
pp. 1631-1639 ◽  
Author(s):  
G P Copenhaver ◽  
E A Housworth ◽  
F W Stahl
Keyword(s):  
Arabidopsis Thaliana ◽  
Degrees Of Freedom ◽  
Double Strand Breaks ◽  
Crossing Over ◽  
Chi Square ◽  
Strand Breaks ◽  
Crossover Interference

AbstractThe crossover distribution in meiotic tetrads of Arabidopsis thaliana differs from those previously described for Drosophila and Neurospora. Whereas a chi-square distribution with an even number of degrees of freedom provides a good fit for the latter organisms, the fit for Arabidopsis was substantially improved by assuming an additional set of crossovers sprinkled, at random, among those distributed as per chi square. This result is compatible with the view that Arabidopsis has two pathways for meiotic crossing over, only one of which is subject to interference. The results further suggest that Arabidopsis meiosis has >10 times as many double-strand breaks as crossovers.

scholarly journals Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sona Gregorova ◽  
Vaclav Gergelits ◽  
Irena Chvatalova ◽  
Tanmoy Bhattacharyya ◽  
Barbora Valiskova ◽  
...  
Keyword(s):  
Meiotic Chromosome ◽  
Hybrid Sterility ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Recombination Hotspots ◽  
Chromosome Synapsis ◽  
Reproductive Isolation Mechanisms ◽  
Meiotic Recombination Hotspots ◽  
Isolation Mechanisms

Hybrid sterility is one of the reproductive isolation mechanisms leading to speciation. Prdm9, the only known vertebrate hybrid-sterility gene, causes failure of meiotic chromosome synapsis and infertility in male hybrids that are the offspring of two mouse subspecies. Within species, Prdm9 determines the sites of programmed DNA double-strand breaks (DSBs) and meiotic recombination hotspots. To investigate the relation between Prdm9-controlled meiotic arrest and asynapsis, we inserted random stretches of consubspecific homology on several autosomal pairs in sterile hybrids, and analyzed their ability to form synaptonemal complexes and to rescue male fertility. Twenty-seven or more megabases of consubspecific (belonging to the same subspecies) homology fully restored synapsis in a given autosomal pair, and we predicted that two or more DSBs within symmetric hotspots per chromosome are necessary for successful meiosis. We hypothesize that impaired recombination between evolutionarily diverged chromosomes could function as one of the mechanisms of hybrid sterility occurring in various sexually reproducing species.

scholarly journals Meiotic condensin is required for proper chromosome compaction, SC assembly, and resolution of recombination-dependent chromosome linkages

2003 ◽  
Vol 163 (5) ◽  
pp. 937-947 ◽  
Author(s):  
Hong-Guo Yu ◽  
Douglas E. Koshland
Keyword(s):  
Mitotic Chromosome ◽  
Chromosome Structure ◽  
Chromosomal Localization ◽  
Meiotic Chromosome ◽  
Chromosome Condensation ◽  
Structure And Function ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Evolutionarily Conserved ◽  
And Function

Condensin is an evolutionarily conserved protein complex that helps mediate chromosome condensation and segregation in mitotic cells. Here, we show that condensin has two activities that contribute to meiotic chromosome condensation in Saccharomyces cerevisiae. One activity, common to mitosis, helps mediate axial length compaction. A second activity promotes chromosome individualization with the help of Red1 and Hop1, two meiotic specific components of axial elements. Like Red1 and Hop1, condensin is also required for efficient homologue pairing and proper processing of double strand breaks. Consistent with these functional links condensin is necessary for proper chromosomal localization of Red1 and Hop1 and the subsequent assembly of the synaptonemal complex. Finally, condensin has a Red1/Hop1-independent role in the resolution of recombination-dependent linkages between homologues in meiosis I. The existence of distinct meiotic activities of condensin (axial compaction, individualization, and resolution of recombination-dependent links) provides an important framework to understand condensin's role in both meiotic and mitotic chromosome structure and function.

scholarly journals What drives recombination hotspots to repeat DNA in humans?

2010 ◽  
Vol 365 (1544) ◽  
pp. 1213-1218 ◽  
Author(s):  
Gil McVean
Keyword(s):  
Active Element ◽  
Rapid Evolution ◽  
Gene Families ◽  
Double Strand Breaks ◽  
Segmental Duplications ◽  
Repeat Elements ◽  
Strand Breaks ◽  
Dna Motifs ◽  
Recombination Hotspots ◽  
Repeat Dna

Recombination between homologous, but non-allelic, stretches of DNA such as gene families, segmental duplications and repeat elements is an important source of mutation. In humans, recent studies have identified short DNA motifs that both determine the location of 40 per cent of meiotic cross-over hotspots and are significantly enriched at the breakpoints of recurrent non-allelic homologous recombination (NAHR) syndromes. Unexpectedly, the most highly penetrant form of the motif occurs on the background of an inactive repeat element family (THE1 elements) and the motif also has strong recombinogenic activity on currently active element families including Alu and LINE2 elements. Analysis of genetic variation among members of these repeat families indicates an important role for NAHR in their evolution. Given the potential for double-strand breaks within repeat DNA to cause pathological rearrangement, the association between repeats and hotspots is surprising. Here we consider possible explanations for why selection acting against NAHR has not eliminated hotspots from repeat DNA including mechanistic constraints, possible benefits to repeat DNA from recruiting hotspots and rapid evolution of the recombination machinery. I suggest that rapid evolution of hotspot motifs may, surprisingly, tend to favour sequences present in repeat DNA and outline the data required to differentiate between hypotheses.

scholarly journals ZCWPW1 is recruited to recombination hotspots by PRDM9 and is essential for meiotic double strand break repair

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Daniel Wells ◽  
Emmanuelle Bitoun ◽  
Daniela Moralli ◽  
Gang Zhang ◽  
Anjali Hinch ◽  
...  
Keyword(s):  
Binding Sites ◽  
Protein S ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dsb Repair ◽  
Strand Breaks ◽  
Homologous Chromosomes ◽  
Cpg Dinucleotides ◽  
Recombination Hotspots ◽  
Highly Correlated

During meiosis, homologous chromosomes pair and recombine, enabling balanced segregation and generating genetic diversity. In many vertebrates, double-strand breaks (DSBs) initiate recombination within hotspots where PRDM9 binds, and deposits H3K4me3 and H3K36me3. However, no protein(s) recognising this unique combination of histone marks have been identified. We identified Zcwpw1, containing H3K4me3 and H3K36me3 recognition domains, as having highly correlated expression with Prdm9. Here, we show that ZCWPW1 has co-evolved with PRDM9 and, in human cells, is strongly and specifically recruited to PRDM9 binding sites, with higher affinity than sites possessing H3K4me3 alone. Surprisingly, ZCWPW1 also recognises CpG dinucleotides. Male Zcwpw1 knockout mice show completely normal DSB positioning, but persistent DMC1 foci, severe DSB repair and synapsis defects, and downstream sterility. Our findings suggest ZCWPW1 recognition of PRDM9-bound sites at DSB hotspots is critical for synapsis, and hence fertility.

scholarly journals Telomere length dynamics in response to DNA damage in malaria parasites

2020 ◽  
Author(s):  
Jake Reed ◽  
Laura A Kirkman ◽  
Bjӧrn FC Kafsack ◽  
Christopher Mason ◽  
Kirk W Deitsch
Keyword(s):  
Double Strand Breaks ◽  
Genome Integrity ◽  
Dna Breaks ◽  
Strand Breaks ◽  
Host Parasite Interactions ◽  
Evolutionarily Conserved ◽  
Long Read ◽  
Host Parasite ◽  
Variant Antigen ◽  
Subtelomeric Regions

SUMMARYMalaria remains a major cause of morbidity and mortality within the developing world. Recent work has implicated chromosome end stability and the repair of DNA breaks through telomere healing as potent drivers of variant antigen diversification, thus associating basic mechanisms for maintaining genome integrity with aspects of host-parasite interactions. Here we applied long-read sequencing technology to precisely examine the dynamics of telomere addition and chromosome end stabilization in response to double strand breaks within subtelomeric regions. We observed that the process of telomere healing induces the initial synthesis of telomere repeats well in excess of the minimal number required for end stability. However once stabilized, these newly created telomeres appear to function normally, eventually returning to a length nearing that of intact chromosome ends. These results parallel recent observations in humans, suggesting an evolutionarily conserved mechanism for chromosome end repair.

scholarly journals Identification of a signature of evolutionarily conserved stress-induced mutagenesis in cancer

2021 ◽  
Author(s):  
Luis Humberto Cisneros ◽  
Kimberly J Bussey ◽  
Charles Vasque
Keyword(s):  
Double Strand Breaks ◽  
Whole Genome Sequencing Data ◽  
Dna Double Strand Breaks ◽  
Sequencing Data ◽  
Single Nucleotide ◽  
Strand Breaks ◽  
Evolutionarily Conserved ◽  
Induced Mutagenesis ◽  
Genomic Locations ◽  
Inherited Mutations

The clustering of mutations observed in cancer cells is reminiscent of the stress-induced mutagenesis (SIM) response in bacteria. SIM employs error-prone polymerases resulting in mutations concentrated around DNA double-strand breaks with an abundance that decays with genomic distance. We performed a quantitative study on single nucleotide variant calls for whole-genome sequencing data from 1950 tumors and non-inherited mutations from 129 normal samples. We introduce statistical methods to identify mutational clusters and quantify their distribution pattern. Our results show that mutations in both normal and cancer samples are indeed clustered and have shapes indicative of SIM. We found the genomic locations of groups of close mutations are more likely to be prevalent across normal samples than in cancer suggesting loss of regulation over the mutational process during carcinogenesis.

scholarly journals Local and sex-specific biases in crossover vs. noncrossover outcomes at meiotic recombination hotspots in mouse

2015 ◽  
Author(s):  
Esther de Boer ◽  
Maria Jasin ◽  
Scott Keeney
Keyword(s):  
Meiotic Recombination ◽  
Chromosomal Location ◽  
Double Strand Breaks ◽  
Chromosome 1 ◽  
Female Meiosis ◽  
Strand Breaks ◽  
Recombination Hotspots ◽  
Cellular Context ◽  
Males And Females ◽  
Meiotic Recombination Hotspots

Meiotic recombination initiated by programmed double-strand breaks (DSBs) yields two types of interhomolog recombination products, crossovers and noncrossovers, but what determines whether a DSB will yield a crossover or noncrossover is not understood. In this study we analyze the influence of sex and chromosomal location on mammalian recombination outcomes by constructing fine-scale recombination maps in both males and females at two mouse hotspots located in different regions of the same chromosome. These include the most comprehensive maps of recombination hotspots in oocytes to date. One hotspot, located centrally on chromosome 1, behaved similarly in male and female meiosis: crossovers and noncrossovers formed at comparable levels and ratios in both sexes. In contrast, at a distal hotspot crossovers were recovered only in males even though noncrossovers were obtained at similar frequencies in both sexes. These findings reveal an example of extreme sex-specific bias in recombination outcome. We further find that estimates of relative DSB levels are surprisingly poor predictors of relative crossover frequencies between hotspots in males. Our results demonstrate that the outcome of mammalian meiotic recombination can be biased, that this bias can vary depending on location and cellular context, and that DSB frequency is not the only determinant of crossover frequency.

scholarly journals The mRNA export adaptor Yra1 contributes to DNA double-strand break repair through its C-box domain

2018 ◽  
Author(s):  
Valentina Infantino ◽  
Evelina Tutucci ◽  
Noël Yeh Martin ◽  
Audrey Zihlmann ◽  
Varinia García-Molinero ◽  
...  
Keyword(s):  
Mrna Export ◽  
Strand Break ◽  
Double Strand Breaks ◽  
Dna Double Strand Breaks ◽  
Nuclear Pores ◽  
Dsb Repair ◽  
Telomere Shortening ◽  
Strand Breaks ◽  
Dna Double Strand Break ◽  
Evolutionarily Conserved

ABSTRACTYra1 is an mRNA export adaptor involved in mRNA biogenesis and export in S. cerevisiae. Yra1 overexpression was recently shown to promote accumulation of DNA:RNA hybrids favoring DNA double strand breaks (DSB), cell senescence and telomere shortening, via an unknown mechanism. Yra1 was also identified at an HO-induced DSB and Yra1 depletion causes defects in DSB repair. Previous work from our laboratory showed that Yra1 ubiquitination by Tom1 is important for mRNA export. Interestingly, we found that Yra1 is also ubiquitinated by the SUMO-targeted ubiquitin ligases Slx5-Slx8 implicated in the interaction of irreparable DSB with nuclear pores. Here we show that Yra1 binds an HO-induced irreparable DSB. Importantly, a Yra1 mutant lacking the evolutionarily conserved C-box is not recruited to an HO-induced irreparable DSB and becomes lethal under DSB induction in a HO-cut reparable system. Together, the data provide evidence that Yra1 plays a crucial role in DSB repair via homologous recombination. Unexpectedly, while the Yra1 C-box is essential, Yra1 sumoylation and/or ubiquitination are dispensable in this process.

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