Explore the vast range of titles available.

• Meiotic recombination rates vary considerably between species, populations and individuals. The genetic exchange between homologous chromosomes plays a major role in evolution by breaking linkage between advantageous and deleterious alleles in the case of introgressions. Identifying recombination rate modifiers is thus of both fundamental and practical interest to understand and utilize variation in meiotic recombination rates. • We investigated recombination rate variation in a large intraspecific hybrid population (named HEB-25) derived from a cross between domesticated barley and 25 wild barley accessions. • We observed quantitative variation in total crossover number with a maximum of a 1.4-fold difference between subpopulations and increased recombination rates across pericentromeric regions. The meiosis-specific α-kleisin cohesin subunit REC8 was identified as a candidate gene influencing crossover number and patterning. Furthermore, we quantified wild barley introgression patterns and revealed how local and genome-wide recombination rate variation shapes patterns of introgression. • The identification of allelic variation in REC8 in combination with the observed changes in crossover patterning suggest a difference in how chromatin loops are tethered to the chromosome axis, resulting in reduced crossover suppression across pericentromeric regions. Local and genome-wide recombination rate variation is shaping patterns of introgressions and thereby directly influences the consequences of linkage drag.

Leafy Legacy Plants can't run from unpleasantness such as too much or too little heat or light. Instead they show varying degrees of tolerance by reacting to stress with a range of physiological responses. Surprisingly, when Arabidopsis thaliana plants are exposed to stress (UV light or a chemical mimicking pathogenic attack), changes are seen not only in the treated plants but also in several generations of their untreated offspring. The plants 'remember' the stress, presumably using an as-yet unknown epigenetic mechanism. Echoes, but only echoes, of the discredited lamarckian idea of chromosomal inheritance of acquired traits. Plants exposed to environmental stresses such as ultraviolet light exhibit increased recombination between homologous chromosomes. Here, the progeny of plants that were exposed to an environmental stress also exhibited increased levels of genetic recombination, even though the progeny were not actually exposed to the stress. Owing to their sessile nature, plants are constantly exposed to a multitude of environmental stresses to which they react with a battery of responses. The result is plant tolerance to conditions such as excessive or inadequate light, water, salt and temperature, and resistance to pathogens. Not only is plant physiology known to change under abiotic or biotic stress, but changes in the genome have also been identified 1 , 2 , 3 , 4 , 5 . However, it was not determined whether plants from successive generations of the original, stressed plants inherited the capacity for genomic change. Here we show that in Arabidopsis thaliana plants treated with short-wavelength radiation (ultraviolet-C) or flagellin (an elicitor of plant defences 6 ), somatic homologous recombination of a transgenic reporter is increased in the treated population and these increased levels of homologous recombination persist in the subsequent, untreated generations. The epigenetic trait of enhanced homologous recombination could be transmitted through both the maternal and the paternal crossing partner, and proved to be dominant. The increase of the hyper-recombination state in generations subsequent to the treated generation was independent of the presence of the transgenic allele (the recombination substrate under consideration) in the treated plant. We conclude that environmental factors lead to increased genomic flexibility even in successive, untreated generations, and may increase the potential for adaptation.

In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination. PRDM9 binds to DNA at hotspots through its zinc finger domain and activates recombination by trimethylating histone H3K4 on adjacent nucleosomes through its PR/SET domain. Recently, the isolated PR/SET domain of PRDM9 was shown capable of also trimethylating H3K36 in vitro, raising the question of whether this reaction occurs in vivo during meiosis, and if so, what its function might be. Here, we show that full-length PRDM9 does trimethylate H3K36 in vivo in mouse spermatocytes. Levels of H3K4me3 and H3K36me3 are highly correlated at hotspots, but mutually exclusive elsewhere. In vitro, we find that although PRDM9 trimethylates H3K36 much more slowly than it does H3K4, PRDM9 is capable of placing both marks on the same histone molecules. In accord with these results, we also show that PRDM9 can trimethylate both K4 and K36 on the same nucleosomes in vivo, but the ratio of K4me3/K36me3 is much higher for the pair of nucleosomes adjacent to the PRDM9 binding site compared to the next pair further away. Importantly, H3K4me3/H3K36me3-double-positive nucleosomes occur only in regions of recombination: hotspots and the pseudoautosomal (PAR) region of the sex chromosomes. These double-positive nucleosomes are dramatically reduced when PRDM9 is absent, showing that this signature is PRDM9-dependent at hotspots; the residual double-positive nucleosomes most likely come from the PRDM9-independent PAR. These results, together with the fact that PRDM9 is the only known mammalian histone methyltransferase with both H3K4 and H3K36 trimethylation activity, suggest that trimethylation of H3K36 plays an important role in the recombination process. Given the known requirement of H3K36me3 for double strand break repair by homologous recombination in somatic cells, we suggest that it may play the same role in meiosis.

Recombination, the process by which DNA strands are broken and repaired, producing new combinations of alleles, occurs in nearly all multicellular organisms and has important implications for many evolutionary processes. The effects of recombination can be good, as it can facilitate adaptation, but also bad when it breaks apart beneficial combinations of alleles, and recombination is highly variable between taxa, species, individuals and across the genome. Understanding how and why recombination rate varies is a major challenge in biology. Most theoretical and empirical work has been devoted to understanding the role of recombination in the evolution of sex—comparing between sexual and asexual species or populations. How recombination rate evolves and what impact this has on evolutionary processes within sexually reproducing organisms has received much less attention. This Theme Issue focusses on how and why recombination rate varies in sexual species, and aims to coalesce knowledge of the molecular mechanisms governing recombination with our understanding of the evolutionary processes driving variation in recombination within and between species. By integrating these fields, we can identify important knowledge gaps and areas for future research, and pave the way for a more comprehensive understanding of how and why recombination rate varies.

One of the most striking patterns of genome structure is the tight, typically negative, association between transposable elements (TEs) and meiotic recombination rates. While this is a highly recurring feature of eukaryotic genomes, the mechanisms driving correlations between TEs and recombination remain poorly understood, and distinguishing cause versus effect is challenging. Here, we review the evidence for a relation between TEs and recombination, and discuss the underlying evolutionary forces. Evidence to date suggests that overall TE densities correlate negatively with recombination, but the strength of this correlation varies across element types, and the pattern can be reversed. Results suggest that heterogeneity in the strength of selection against ectopic recombination and gene disruption can drive TE accumulation in regions of low recombination, but there is also strong evidence that the regulation of TEs can influence local recombination rates. We hypothesize that TE insertion polymorphism may be important in driving within-species variation in recombination rates in surrounding genomic regions. Furthermore, the interaction between TEs and recombination may create positive feedback, whereby TE accumulation in non-recombining regions contributes to the spread of recombination suppression. Further investigation of the coevolution between recombination and TEs has important implications for our understanding of the evolution of recombination rates and genome structure. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.

Hybridisation and introgression can dramatically alter the relationships among groups of species, leading to phylogenetic discordance across the genome and between populations. Introgression can also erode species differences over time, but selection against introgression at certain loci acts to maintain postmating species barriers. Theory predicts that species barriers made up of many loci throughout the genome should lead to a broad correlation between introgression and recombination rate, which determines the extent to which selection on deleterious foreign alleles will affect neutral alleles at physically linked loci. Here, we describe the variation in genealogical relationships across the genome among three species of Heliconius butterflies: H. melpomene (mel), H. cydno (cyd), and H. timareta (tim), using whole genomes of 92 individuals, and ask whether this variation can be explained by heterogeneous barriers to introgression. We find that species relationships vary predictably at the chromosomal scale. By quantifying recombination rate and admixture proportions, we then show that rates of introgression are predicted by variation in recombination rate. This implies that species barriers are highly polygenic, with selection acting against introgressed alleles across most of the genome. In addition, long chromosomes, which have lower recombination rates, produce stronger barriers on average than short chromosomes. Finally, we find a consistent difference between two species pairs on either side of the Andes, which suggests differences in the architecture of the species barriers. Our findings illustrate how the combined effects of hybridisation, recombination, and natural selection, acting at multitudes of loci over long periods, can dramatically sculpt the phylogenetic relationships among species.

Recombination, the exchange of DNA between maternal and paternal chromosomes during meiosis, is an essential feature of sexual reproduction in nearly all multicellular organisms. While the role of recombination in the evolution of sex has received theoretical and empirical attention, less is known about how recombination rate itself evolves and what influence this has on evolutionary processes within sexually reproducing organisms. Here, we explore the patterns of, and processes governing recombination in eukaryotes. We summarize patterns of variation, integrating current knowledge with an analysis of linkage map data in 353 organisms. We then discuss proximate and ultimate processes governing recombination rate variation and consider how these influence evolutionary processes. Genome-wide recombination rates (cM/Mb) can vary more than tenfold across eukaryotes, and there is large variation in the distribution of recombination events across closely related taxa, populations and individuals. We discuss how variation in rate and distribution relates to genome architecture, genetic and epigenetic mechanisms, sex, environmental perturbations and variable selective pressures. There has been great progress in determining the molecular mechanisms governing recombination, and with the continued development of new modelling and empirical approaches, there is now also great opportunity to further our understanding of how and why recombination rate varies. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.

Hot spots for meiotic recombination To initiate the recombination process that guides accurate chromosome segregation during meiosis, programmed double-strand breaks are made at preferred sites known as hot spots. Petukhova and colleagues have now achieved high-resolution genome-wide mapping of meiotic double-strand breaks in mouse cells. The method employed is independent of the availability of genetic markers, a limitation of previous approaches. With these data they have uncovered several features of hot spots at both the sequence and chromatin levels. Meiotic recombination predominantly occurs at discrete genomic loci called recombination hotspots, but the features defining these areas are still largely unknown (reviewed in refs 1–5 ). To allow a comprehensive analysis of hotspot-associated DNA and chromatin characteristics, we developed a direct molecular approach for mapping meiotic DNA double-strand breaks that initiate recombination. Here we present the genome-wide distribution of recombination initiation sites in the mouse genome. Hotspot centres are mapped with approximately 200-nucleotide precision, which allows analysis of the fine structural details of the preferred recombination sites. We determine that hotspots share a centrally distributed consensus motif, possess a nucleotide skew that changes polarity at the centres of hotspots and have an intrinsic preference to be occupied by a nucleosome. Furthermore, we find that the vast majority of recombination initiation sites in mouse males are associated with testis-specific trimethylation of lysine 4 on histone H3 that is distinct from histone H3 lysine 4 trimethylation marks associated with transcription. The recombination map presented here has been derived from a homogeneous mouse population with a defined genetic background and therefore lends itself to extensive future experimental exploration. We note that the mapping technique developed here does not depend on the availability of genetic markers and hence can be easily adapted to other species with complex genomes. Our findings uncover several fundamental features of mammalian recombination hotspots and underline the power of the new recombination map for future studies of genetic recombination, genome stability and evolution.

Comparison of Prdm9 −/− and wild-type mice reveals a role for the PRDM9 protein in directing the recombination machinery away from important genomic regions. Functional genes protected during recombination PRDM9, a histone H3 methyltransferase, is thought to determine the location of recombination hotspots through sequence-specific binding. By genome-wide mapping of hotspots in mice that carry different Prdm9 alleles, Galina Petukhova and colleagues conclude that PRDM9 determines the positions of almost all hotspots in the mouse genome, apart from those in the pseudo-autosomal region. A comparison of preferential locations of recombination initiation sites in the absence of PRDM9 and in wild-type mice reveals an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements. Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9) 1 , 2 , 3 , 4 , 5 , 6 , the product of the only known speciation-associated gene in mammals 7 . PRDM9 is thought to determine the preferred recombination sites—recombination hotspots—through sequence-specific binding of its highly polymorphic multi-Zn-finger domain 8 . Nevertheless, Prdm9 knockout mice are proficient at initiating recombination 9 . Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F 1 hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)—the only area of the genome that undergoes recombination in 100% of cells 10 . Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements.

Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve PA-Cre technology, we compare light-dimerization tools and optimize for mammalian expression using a CAG promoter, Magnets, and 2A self-cleaving peptide. To prevent background recombination caused by the high sequence similarity in the dimerization domains, we modify the codons for mouse gene targeting and viral production. Overall, these modifications significantly reduce dark leak activity and improve blue-light induction developing our new version, PA-Cre 3.0. As a resource, we have generated and validated AAV-PA-Cre 3.0 as well as two mouse lines that can conditionally express PA-Cre 3.0. Together these new tools will facilitate further biological and biomedical research. Previous versions of photoactivatable Cre recombinase (PA-Cre) suffered from unintentional recombination in dark conditions. Here, the authors develop an improved version of PA-Cre, called PA-Cre 3.0, which shows reduced leakiness and improved efficiency upon activation, and make mouse lines that express PA-Cre 3.0 conditionally.