scholarly journals Genome-wide recombination map construction from single individuals using linked-read sequencing

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Andreea Dréau ◽  
Vrinda Venu ◽  
Elena Avdievich ◽  
Ludmila Gaspar ◽  
Felicity C. Jones
Keyword(s):  
Meiotic Recombination ◽  
Molecular Basis ◽  
Low Cost ◽  
Single Individual ◽  
Recombination Rates ◽  
Recombination Hotspots ◽  
Map Construction ◽  
Genome Wide ◽  
Genomic Location ◽  
Exciting Opportunity

Abstract Meiotic recombination rates vary across the genome, often involving localized crossover hotspots and coldspots. Studying the molecular basis and mechanisms underlying this variation has been challenging due to the high cost and effort required to construct individualized genome-wide maps of recombination crossovers. Here we introduce a new method, called ReMIX, to detect crossovers from gamete DNA of a single individual using Illumina sequencing of 10X Genomics linked-read libraries. ReMIX reconstructs haplotypes and identifies the valuable rare molecules spanning crossover breakpoints, allowing quantification of the genomic location and intensity of meiotic recombination. Using a single mouse and stickleback fish, we demonstrate how ReMIX faithfully recovers recombination hotspots and landscapes that have previously been built using hundreds of offspring. ReMIX provides a high-resolution, high-throughput, and low-cost approach to quantify recombination variation across the genome, providing an exciting opportunity to study recombination among multiple individuals in diverse organisms.

scholarly journals Genome-wide recombination map construction from single individuals using linked-read sequencing

2018 ◽  
Author(s):  
Andreea Dréau ◽  
Vrinda Venu ◽  
Ludmila Gaspar ◽  
Felicity C. Jones
Keyword(s):  
Low Cost ◽  
Genomic Diversity ◽  
Single Individual ◽  
Recombination Rates ◽  
Recombination Hotspots ◽  
Map Construction ◽  
Genome Wide ◽  
Genomic Location ◽  
Sperm Dna ◽  
Opening Up

Meiotic recombination is a major molecular mechanism generating genomic diversity. Recombination rates vary across the genome, often involving localized crossover “hotspots” and “coldspots”. Studying the molecular basis and mechanism underlying this variation within and among individuals has been challenging due to the high cost and effort required to construct individualized genome-wide maps of recombination crossovers. In this study we introduce a new method to detect recombination crossovers across the genome from sperm DNA using Illumina sequencing of linked-read libraries produced using 10X Genomics technology. We leverage the long range information provided by the linked short reads to phase and assign haplotype states to each DNA molecule. When applied to DNA from gametes of a diploid organism, the majority of linked-read molecules can be used to faithfully reconstruct an individual’s two haplotypes present at each location in the genome. A valuable rare fraction of molecules that span meiotic crossovers between the two chromosome haplotypes can then be isolated from the broader population of nonrecombinant molecules. Our pipeline, called ReMIX, allows us to characterize the genomic location and intensity of meiotic crossovers in a single individual and faithfully detects previously described recombination hotspots discovered by studies using mapping panels in mice. With a median crossover resolution of the mouse and stickleback being 15kb and 23kb respectively, ReMIX provides a powerful, high-throughput, low-cost approach to quantify recombination variation across the genome opening up numerous opportunities to study recombination variation with high genomic resolution in multiple individuals. ReMIX source code is available at at https://github.com/adreau/ReMIX.

scholarly journals Concerted action of the MutLβ heterodimer and Mer3 helicase regulates the global extent of meiotic gene conversion

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yann Duroc ◽  
Rajeev Kumar ◽  
Lepakshi Ranjha ◽  
Céline Adam ◽  
Raphaël Guérois ◽  
...  
Keyword(s):  
Gene Conversion ◽  
Meiotic Recombination ◽  
Recombination Hotspots ◽  
Genome Wide ◽  
D Loop ◽  
Mismatch Recognition ◽  
Gene Conversion Tract ◽  
Gene Conversions ◽  
Conversion Tract

Gene conversions resulting from meiotic recombination are critical in shaping genome diversification and evolution. How the extent of gene conversions is regulated is unknown. Here we show that the budding yeast mismatch repair related MutLβ complex, Mlh1-Mlh2, specifically interacts with the conserved meiotic Mer3 helicase, which recruits it to recombination hotspots, independently of mismatch recognition. This recruitment is essential to limit gene conversion tract lengths genome-wide, without affecting crossover formation. Contrary to expectations, Mer3 helicase activity, proposed to extend the displacement loop (D-loop) recombination intermediate, does not influence the length of gene conversion events, revealing non-catalytical roles of Mer3. In addition, both purified Mer3 and MutLβ preferentially recognize D-loops, providing a mechanism for limiting gene conversion in vivo. These findings show that MutLβ is an integral part of a new regulatory step of meiotic recombination, which has implications to prevent rapid allele fixation and hotspot erosion in populations.

Meiotic recombination hotspots in plants

2006 ◽  
Vol 34 (4) ◽  
pp. 531-534 ◽  
Author(s):  
C. Mézard
Keyword(s):  
Plant Species ◽  
Meiotic Recombination ◽  
Large Scale ◽  
Genetic Recombination ◽  
Dna Fragments ◽  
Recombination Rates ◽  
Coding Regions ◽  
Recombination Hotspots ◽  
Meiotic Recombination Hotspots

Many studies have demonstrated that the distribution of meiotic crossover events along chromosomes is non-random in plants and other species with sexual reproduction. Large differences in recombination frequencies appear at several scales. On a large scale, regions of high and low rates of crossover have been found to alternate along the chromosomes in all plant species studied. High crossover rates have been reported to be correlated with several chromosome features (e.g. gene density and distance to the centromeres). However, most of these correlations cannot be extended to all plant species. Only a few plant species have been studied on a finer scale. Hotspots of meiotic recombination (i.e. DNA fragments of a few kilobases in length with a higher rate of recombination than the surrounding DNA) have been identified in maize and rice. Most of these hotspots are intragenic. In Arabidopsis thaliana, we have identified several DNA fragments (less than 5 kb in size) with genetic recombination rates at least 5 times higher than the whole-chromosome average [4.6 cM (centimorgan)/Mb], which are therefore probable hotspots for meiotic recombination. Most crossover breakpoints lie in intergenic or non-coding regions. Major efforts should be devoted to characterizing meiotic recombination at the molecular level, which should help to clarify the role of this process in genome evolution.

scholarly journals Variation in recombination rate and its genetic determinism in sheep (Ovis Aries) populations from combining multiple genome-wide datasets

2017 ◽  
Author(s):  
Morgane Petit ◽  
Jean-Michel Astruc ◽  
Julien Sarry ◽  
Laurence Drouilhet ◽  
Stéphane Fabre ◽  
...  
Keyword(s):  
Meiotic Recombination ◽  
Individual Variation ◽  
Recombination Rate ◽  
Snp Array ◽  
Genetic Determinism ◽  
Ovis Aries ◽  
Domestic Sheep ◽  
Recombination Rates ◽  
Male Recombination ◽  
Genome Wide

AbstractRecombination is a complex biological process that results from a cascade of multiple events during meiosis. Understanding the genetic determinism of recombination can help to understand if and how these events are interacting. To tackle this question, we studied the patterns of recombination in sheep, using multiple approaches and datasets. We constructed male recombination maps in a dairy breed from the south of France (the Lacaune breed) at a fine scale by combining meiotic recombination rates from a large pedigree genotyped with a 50K SNP array and historical recombination rates from a sample of unrelated individuals genotyped with a 600K SNP array. This analysis revealed recombination patterns in sheep similar to other mammals but also genome regions that have likely been affected by directional and diversifying selection. We estimated the average recombination rate of Lacaune sheep at 1.5 cM/Mb, identified about 50,000 crossover hotspots on the genome and found a high correlation between historical and meiotic recombination rate estimates. A genome-wide association study revealed two major loci affecting inter-individual variation in recombination rate in Lacaune, including the RNF212 and HEI10 genes and possibly 2 other loci of smaller effects including the KCNJ15 and FSHR genes. Finally, we compared our results to those obtained previously in a distantly related population of domestic sheep, the Soay. This comparison revealed that Soay and Lacaune males have a very similar distribution of recombination along the genome and that the two datasets can be combined to create more precise male meiotic recombination maps in sheep. Despite their similar recombination maps, we show that Soay and Lacaune males exhibit different heritabilities and QTL effects for inter-individual variation in genome-wide recombination rates.

scholarly journals A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Nicolas Altemose ◽  
Nudrat Noor ◽  
Emmanuelle Bitoun ◽  
Afidalina Tumian ◽  
Michael Imbeault ◽  
...  
Keyword(s):  
Histone Modifications ◽  
Meiotic Recombination ◽  
Binding Sites ◽  
Human Cell Line ◽  
Sequence Motifs ◽  
Recombination Rates ◽  
Recombination Suppression ◽  
Specific Sequence ◽  
Recombination Hotspots ◽  
Almost All

PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.

scholarly journals A Coalescent Model of Recombination Hotspots

Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 407-417 ◽  
Author(s):  
Carsten Wiuf ◽  
David Posada
Keyword(s):  
Current Debate ◽  
Expected Number ◽  
Recombination Rates ◽  
Coalescent Model ◽  
Recombination Hotspots ◽  
Snp Data ◽  
Genome Wide ◽  
Experimental Findings ◽  
Historical Recombination ◽  
Block Structured

Abstract Recent experimental findings suggest that the assumption of a homogeneous recombination rate along the human genome is too naive. These findings point to block-structured recombination rates; certain regions (called hotspots) are more prone than other regions to recombination. In this report a coalescent model incorporating hotspot or block-structured recombination is developed and investigated analytically as well as by simulation. Our main results can be summarized as follows: (1) The expected number of recombination events is much lower in a model with pure hotspot recombination than in a model with pure homogeneous recombination, (2) hotspots give rise to large variation in recombination rates along the genome as well as in the number of historical recombination events, and (3) the size of a (nonrecombining) block in the hotspot model is likely to be overestimated grossly when estimated from SNP data. The results are discussed with reference to the current debate about block-structured recombination and, in addition, the results are compared to genome-wide variation in recombination rates. A number of new analytical results about the model are derived.

Evolution and Plasticity of Genome-Wide Meiotic Recombination Rates

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Ian R. Henderson ◽  
Kirsten Bomblies
Keyword(s):  
Chromosome Segregation ◽  
Meiotic Recombination ◽  
Recombination Rate ◽  
Empirical Studies ◽  
Annual Review ◽  
Publication Date ◽  
Recombination Rates ◽  
Homologous Chromosomes ◽  
Genome Wide ◽  
Mechanistic Basis

Sex, as well as meiotic recombination between homologous chromosomes, is nearly ubiquitous among eukaryotes. In those species that use it, recombination is important for chromosome segregation during gamete production, and thus for fertility. Strikingly, although in most species only one crossover event per chromosome is required to ensure proper segregation, recombination rates vary considerably above this minimum and show variation within and among species. However, whether this variation in recombination is adaptive or neutral and what might shape it remain unclear. Empirical studies and theory support the idea that recombination is generally beneficial but can also have costs. Here, we review variation in genome-wide recombination rates, explore what might cause this, and discuss what is known about its mechanistic basis. We end by discussing the environmental sensitivity of meiosis and recombination rates, how these features may relate to adaptation, and their implications for a broader understanding of recombination rate evolution. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Recombining without hotspots: A comprehensive evolutionary portrait of recombination in two closely related species of Drosophila

2015 ◽  
Author(s):  
Caiti Smukowski Heil ◽  
Chris Ellison ◽  
Matthew Dubin ◽  
Mohamed Noor
Keyword(s):  
Recombination Rate ◽  
Multiple Scales ◽  
Sequence Data ◽  
Scale Effects ◽  
Recombination Rates ◽  
Recombination Hotspots ◽  
Genome Wide ◽  
Genomic Landscape ◽  
Species Specific

Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in Metazoans by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present what may be the most comprehensive portrait of recombination to date, combining contemporary recombination estimates from each of two sister species along with historic estimates of recombination using linkage-disequilibrium-based approaches derived from sequence data from both species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we replicate the pattern seen in human-chimpanzee that recombination rate is conserved at broad scales and more divergent at finer scales. We also find evidence of a species-wide recombination modifier, resulting in both a present and historic genome wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inter-species inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms.

scholarly journals Chromosomal assembly and analyses of genome-wide recombination rates in the forest pathogenic fungus Armillaria ostoyae

2019 ◽  
Author(s):  
Renate Heinzelmann ◽  
Daniel Rigling ◽  
György Sipos ◽  
Martin Münsterkötter ◽  
Daniel Croll
Keyword(s):  
Pathogenic Fungus ◽  
Snp Markers ◽  
Rate Variation ◽  
Recombination Rates ◽  
Evolutionary Trajectory ◽  
Armillaria Ostoyae ◽  
Recombination Hotspots ◽  
Genome Wide ◽  
A Genome ◽  
Taxonomic Groups

AbstractRecombination shapes the evolutionary trajectory of populations and plays an important role in the faithful transmission of chromosomes during meiosis. Levels of sexual reproduction and recombination are important properties of host-pathogen interactions because the speed of antagonistic co-evolution depends on the ability of hosts and pathogens to generate genetic variation. However, our understanding of the importance of recombination is limited because large taxonomic groups remain poorly investigated. Here, we analyze recombination rate variation in the basidiomycete fungus Armillaria ostoyae, which is an aggressive pathogen on a broad range of conifers and other trees. We constructed a dense genetic map using 198 single basidiospore progeny from a cross. Progeny were genotyped at a genome-wide set of single nucleotide polymorphism (SNP) markers using double digest restriction site associated DNA sequencing (ddRADseq). Based on a linkage map of on 11,700 SNPs spanning 1007.5 cM, we assembled genomic scaffolds into 11 putative chromosomes of a total genome size of 56.6 Mb. We identified 1984 crossover events among all progeny and found that recombination rates were highly variable along chromosomes. Recombination hotspots tended to be in regions close to the telomeres and were more gene-poor than the genomic background. Genes in proximity to recombination hotspots were encoding on average shorter proteins and were enriched for pectin degrading enzymes. Our analyses enable more powerful population and genome-scale studies of a major tree pathogen.

Human polymorphism around recombination hotspots

2006 ◽  
Vol 34 (4) ◽  
pp. 535-536 ◽  
Author(s):  
C.C.A. Spencer
Keyword(s):  
Meiotic Recombination ◽  
Double Strand Breaks ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Strand Breaks ◽  
Recombination Hotspots ◽  
Genome Wide ◽  
Variation Data ◽  
Human Polymorphism ◽  
Fixation Bias

Meiotic recombination in humans is thought to occur as part of the resolution of DSBs (double-strand breaks). The repair of DSBs potentially leads to biases in DNA repair that can distort the population frequency of the alleles at single-nucleotide polymorphisms. Genome-wide variation data provide evidence for a weak fixation bias in favour of G and C alleles that is strongest at the centre of inferred recombination hotspots.

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