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

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.

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Modeling Linkage Disequilibrium and Identifying Recombination Hotspots Using Single-Nucleotide Polymorphism Data

Genetics ◽

10.1093/genetics/165.4.2213 ◽

2003 ◽

Vol 165 (4) ◽

pp. 2213-2233 ◽

Cited By ~ 41

Author(s):

Na Li ◽

Matthew Stephens

Keyword(s):

Linkage Disequilibrium ◽

Recombination Rate ◽

Population Sample ◽

Simulated Data ◽

Region Of Interest ◽

Population Data ◽

Recombination Rates ◽

Single Nucleotide ◽

Recombination Hotspots ◽

Genomic Regions

AbstractWe introduce a new statistical model for patterns of linkage disequilibrium (LD) among multiple SNPs in a population sample. The model overcomes limitations of existing approaches to understanding, summarizing, and interpreting LD by (i) relating patterns of LD directly to the underlying recombination process; (ii) considering all loci simultaneously, rather than pairwise; (iii) avoiding the assumption that LD necessarily has a “block-like” structure; and (iv) being computationally tractable for huge genomic regions (up to complete chromosomes). We examine in detail one natural application of the model: estimation of underlying recombination rates from population data. Using simulation, we show that in the case where recombination is assumed constant across the region of interest, recombination rate estimates based on our model are competitive with the very best of current available methods. More importantly, we demonstrate, on real and simulated data, the potential of the model to help identify and quantify fine-scale variation in recombination rate from population data. We also outline how the model could be useful in other contexts, such as in the development of more efficient haplotype-based methods for LD mapping.

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Evolution of the Yeast Recombination Landscape

Molecular Biology and Evolution ◽

10.1093/molbev/msy233 ◽

2018 ◽

Vol 36 (2) ◽

pp. 412-422 ◽

Cited By ~ 4

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.

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Effect of Heterogeneity in Recombination Rate on Variation in Realised Relationship

10.1101/341776 ◽

2018 ◽

Author(s):

Ian M.S. White ◽

William G. Hill

Keyword(s):

Recombination Rate ◽

Genetic Information ◽

Fine Scale ◽

Recombination Rates ◽

Recombination Hotspots ◽

Identical By Descent ◽

Small Influence ◽

Scale Levels ◽

Pedigree Relationship ◽

Actual Relationship

ABSTRACTIndividuals of specified pedigree relationship vary in the proportion of the genome they share identical by descent, i.e. in their realised or actual relationship. Basing predictions of the variance in realised relationship solely on the proportion of the map length shared implicitly assumes that both recombination rate and genetic information are uniformly distributed along the genome, ignoring the possible existence of recombination hotspots, and failing to distinguish between coding and non-coding sequences. In this paper we quantify the effects of heterogeneity in recombination rate at broad and fine scale levels on the variation in realised relationship. A chromosome with variable recombination rate usually shows more variance in realised relationship than does one having the same map length with constant recombination rate, especially if recombination rates are higher towards chromosome ends. Reductions in variance can also be found, and the overall pattern of change is quite complex. In general, local (fine-scale) variation in recombination rate, e.g. hotspots, has a small influence on the variance in realised relationship. Differences in rates across longer regions and between chromosome ends can increase or decrease the variance in realised relationship, depending on the genomic architecture.

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A glance at recombination hotspots in the domestic cat

10.1101/028043 ◽

2015 ◽

Author(s):

Hasan Alhaddad ◽

Chi Zhang ◽

Bruce Rannala ◽

Leslie A Lyons

Keyword(s):

Recombination Rate ◽

Gc Content ◽

Domestic Cat ◽

Recombination Rates ◽

Recombination Hotspots ◽

Regional Population ◽

Variable Population ◽

Line Elements ◽

Population Recombination ◽

Region Size

Recombination has essential roles in increasing genetic variability within a population and in ensuring successful meiotic events. The objective of this study is to (i) infer the population scaled recombination rate (ρ), and (ii) identify and characterize localities of increased recombination rate for the domestic cat, Felis silvestris catus. SNPs (n = 701) were genotyped in twenty-two cats of Eastern random bred origin. The SNPs covered ten different chromosomal regions (A1, A2, B3, C2, D1, D2, D4, E2, F2, X) with an average region size of 850 Kb and an average SNP density of 70 SNPs/region. The Bayesian method in the program inferRho was used to infer regional population recombination rates and hotspots localities. The regions exhibited variable population recombination rates and four decisive recombination hotspots were identified on cat chromosome A2, D1, and E2 regions. No correlation was detected between the GC content and the locality of recombination spots. The hotspots enclosed L2 LINE elements and MIR and tRNA-Lys SINE elements in agreement with hotspots found in other mammals.

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

10.1101/489989 ◽

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.

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Evidence for widespread selection in shaping the genomic landscape during speciation of Populus

10.1101/819219 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jing Wang ◽

Nathaniel R. Street ◽

Eung-Jun Park ◽

Jianquan Liu ◽

Pär K. Ingvarsson

Keyword(s):

Recurrent Selection ◽

Balancing Selection ◽

Forest Tree ◽

Species Variation ◽

Recombination Rates ◽

Genome Wide ◽

Genomic Landscape ◽

Speciation Continuum ◽

Whole Genome Resequencing

AbstractIncreasing our understanding of how various evolutionary processes drive the genomic landscape of variation is fundamental to a better understanding of the genomic consequences of speciation. However, the genome-wide patterns of within- and between-species variation have not been fully investigated in most forest tree species despite their global ecological and economic importance. Here, we use whole-genome resequencing data from four Populus species spanning the speciation continuum to reconstruct their demographic histories, investigate patterns of diversity and divergence, infer their genealogical relationships and estimate the extent of ancient introgression across the genome. Our results show substantial variation in these patterns along the genomes although this variation is not randomly distributed but is strongly predicted by the local recombination rates and the density of functional elements. This implies that the interaction between recurrent selection and intrinsic genomic features has dramatically sculpted the genomic landscape over long periods of time. In addition, our findings provide evidence that, apart from background selection, recent positive selection and long-term balancing selection are also crucial components in shaping patterns of genome-wide variation during the speciation process.

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ON THE FREQUENCY OF UNDETECTABLE RECOMBINATION EVENTS

Genetics ◽

10.1093/genetics/112.4.923 ◽

1986 ◽

Vol 112 (4) ◽

pp. 923-926

Author(s):

J Claiborne Stephens

Keyword(s):

Population Size ◽

Dna Sequence ◽

Mutation Rate ◽

Recombination Rate ◽

Sequence Data ◽

Recombination Rates ◽

Dna Sequence Data ◽

Analytical Results

ABSTRACT Simple analytical results show that many recombination events occur in such a way as to have no effect on the resultant DNA sequence. The proportion of these undetectable events depends on the population size, mutation rate and recombination rate and is quite large for reasonable values of these quantities. Efforts to estimate recombination rates and frequencies directly from DNA sequence data must, therefore, take this undetectable fraction into account.

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Genetic differentiation and intrinsic genomic features explain variation in recombination hotspots among cocoa tree populations

10.1101/482299 ◽

2018 ◽

Cited By ~ 1

Author(s):

Enrique J. Schwarzkopf ◽

Juan C. Motamayor ◽

Omar E. Cornejo

Keyword(s):

Genetic Differentiation ◽

Recombination Rate ◽

Plant Domestication ◽

Population Divergence ◽

Sequence Motifs ◽

Recombination Rates ◽

Genomic Features ◽

Recombination Hotspots ◽

Genomic Locations ◽

Dna Sequence Motifs

AbstractOur study investigates the possible drivers of recombination hotspots in Theobroma cacao using ten genetically differentiated populations. By comparing recombination patterns between multiple populations, we obtain a novel view of recombination at the population-divergence timescale. For each population, a fine-scale recombination map was generated using the coalescent with a standard method based on linkage disequilibrium (LD). These maps revealed higher recombination rates in a domesticated population and a population that has undergone a recent bottleneck. We inferred hotspots of recombination for each population and find that the genomic locations of hotspots correlate with genetic differentiation between populations (FST). We used randomization approaches to generate appropriate null models to understand the association between hotspots of recombination and both DNA sequence motifs and genomic features. We found that hotspot regions contained fewer known retroelement sequences than expected and were overrepresented near transcription start and termination sites. Our findings indicate that recombination hotspots are evolving in a way that is consistent with genetic differentiation but are also preferentially driven to near coding regions. We illustrate that, consistent with predictions in plant domestication, the recombination rate of the domesticated population is orders of magnitude higher than that of other populations. More importantly, we find two fixed mutations in the domesticated population’s FIGL1 protein. FIGL1 has been shown to increase recombination rates in Arabidopsis by several orders of magnitude, suggesting a possible mechanism for the observed increased recombination rate in the domesticated population.

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

10.1101/104976 ◽

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.

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

Nature Communications ◽

10.1038/s41467-019-12210-9 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 10

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.

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