Snake Recombination Landscapes Are Concentrated in Functional Regions despite PRDM9

Abstract Meiotic recombination in vertebrates is concentrated in hotspots throughout the genome. The location and stability of hotspots have been linked to the presence or absence of PRDM9, leading to two primary models for hotspot evolution derived from mammals and birds. Species with PRDM9-directed recombination have rapid turnover of hotspots concentrated in intergenic regions (i.e., mammals), whereas hotspots in species lacking PRDM9 are concentrated in functional regions and have greater stability over time (i.e., birds). Snakes possess PRDM9, yet virtually nothing is known about snake recombination. Here, we examine the recombination landscape and test hypotheses about the roles of PRDM9 in rattlesnakes. We find substantial variation in recombination rate within and among snake chromosomes, and positive correlations between recombination rate and gene density, GC content, and genetic diversity. Like mammals, snakes appear to have a functional and active PRDM9, but rather than being directed away from genes, snake hotspots are concentrated in promoters and functional regions—a pattern previously associated only with species that lack a functional PRDM9. Snakes therefore provide a unique example of recombination landscapes in which PRDM9 is functional, yet recombination hotspots are associated with functional genic regions—a combination of features that defy existing paradigms for recombination landscapes in vertebrates. Our findings also provide evidence that high recombination rates are a shared feature of vertebrate microchromosomes. Our results challenge previous assumptions about the adaptive role of PRDM9 and highlight the diversity of recombination landscape features among vertebrate lineages.

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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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Patterns of DNA Variability at X-Linked Loci in Mus domesticus

Genetics ◽

10.1093/genetics/147.3.1303 ◽

1997 ◽

Vol 147 (3) ◽

pp. 1303-1316

Author(s):

Michael W Nachman

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

House Mouse ◽

Recombination Rate ◽

Nucleotide Diversity ◽

Mus Domesticus ◽

Substantial Variation ◽

Intraspecific Polymorphism ◽

Recombination Rates ◽

Interspecific Divergence

Introns of four X-linked genes (Hprt, Plp, Glra2, and Amg) were sequenced to provide an estimate of nucleotide diversity at nuclear genes within the house mouse and to test the neutral prediction that the ratio of intraspecific polymorphism to interspecific divergence is the same for different loci. Hprt and Plp lie in a region of the X chromosome that experiences relatively low recombination rates, while Glra2 and Amg lie near the telomere of the X chromosome, a region that experiences higher recombination rates. A total of 6022 bases were sequenced in each of 10 Mus domesticus and one M. caroli. Average nucleotide diversity (π) for introns within M. domesticus was quite low (π = 0.078%). However, there was substantial variation in the level of heterozygosity among loci. The two telomeric loci, Glra2 and Amg, had higher ratios of polymorphism to divergence than the two loci experiencing lower recombination rates. These results are consistent with the hypothesis that heterozygosity is reduced in regions with lower rates of recombination, although sampling of additional genes is needed to establish whether there is a general correlation between heterozygosity and recombination rate as in Drosophila melanogaster.

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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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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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Significant positive correlation between the recombination rate and GC content in the human pseudoautosomal region

Genome ◽

10.1139/g05-124 ◽

2006 ◽

Vol 49 (5) ◽

pp. 413-419 ◽

Cited By ~ 6

Author(s):

Jin-Feng Chen ◽

Fei Lu ◽

Su-Shing Chen ◽

Shi-Heng Tao

Keyword(s):

Recombination Rate ◽

Base Composition ◽

Significant Positive Correlation ◽

Gc Content ◽

Pseudoautosomal Region ◽

Positive Correlation ◽

Coding Regions ◽

Ideal System ◽

Fixation Bias

This paper establishes that recombination drives the evolution of GC content in a significant way. Because the human P-arm pseudoautosomal region (PAR1) has been shown to have a high recombination rate, at least 20-fold more frequent than the genomic average of ~1 cM/Mb, this region provides an ideal system to study the role of recombination in the evolution of base composition. Nine non-coding regions of PAR1 are analyzed in this study. We have observed a highly significant positive correlation between the recombination rate and GC content (ρ = 0.837, p ≤ 0.005). Five regions that lie in the distal part of PAR1 are shown to be significantly higher than genomic average divergence. By comparing the intra- and inter-specific AT→GC – GC→AT ratios, we have detected no fixation bias toward GC alleles except for L254915, which has excessive AT→GC changes in the human lineage. Thus, we conclude that the high GC content of the PAR1 genes better fits the biased gene conversion (BGC) model.Key words: pseudoautosomal region, GC content, base composition, evolution, recombination.

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Meiotic recombination hotspots in plants

Biochemical Society Transactions ◽

10.1042/bst0340531 ◽

2006 ◽

Vol 34 (4) ◽

pp. 531-534 ◽

Cited By ~ 75

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.

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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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Contrasting patterns of sequence divergence and base composition between Drosophila introns and intergenic regions

Biology Letters ◽

10.1098/rsbl.2006.0521 ◽

2006 ◽

Vol 2 (4) ◽

pp. 604-607 ◽

Cited By ~ 10

Author(s):

Lino Ometto ◽

David De Lorenzo ◽

Wolfgang Stephan

Keyword(s):

Drosophila Melanogaster ◽

Recombination Rate ◽

Base Composition ◽

Gc Content ◽

Sequence Divergence ◽

Evolutionary Patterns ◽

Nucleotide Variability ◽

Selective Constraints ◽

Intergenic Regions

Two non-coding DNA classes, introns and intergenic regions, of Drosophila melanogaster exhibit contrasting evolutionary patterns. GC content is significantly higher in intergenic regions and affects their degree of nucleotide variability. Divergence is positively correlated with recombination rate in intergenic regions, but not in introns. We argue that these differences are due to different selective constraints rather than mutational or recombinational mechanisms.

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Big data reveals fewer recombination hotspots than expected in human genome

10.1101/809020 ◽

2019 ◽

Author(s):

Ziqian Hao ◽

Haipeng Li

Keyword(s):

Artificial Intelligence ◽

Sample Size ◽

Recombination Rate ◽

Genetic Maps ◽

Recombination Activity ◽

Recombination Rates ◽

Accurate Identification ◽

Data Set ◽

Recombination Hotspots ◽

Precise Estimation

AbstractRecombination is a major force that shapes genetic diversity. The inference accuracy of recombination rate is important and can be improved by increasing sample size. However, it has never been investigated whether sample size affects the distribution of inferred recombination activity along the genome, and the inference of recombination hotspots. In this study, we applied an artificial intelligence approach to estimate recombination rates in the UK10K human genomic data set with 7,562 genomes and in the OMNI CEU data set with 170 genomes. We found that the fluctuation of local recombination rate along the UK10K genomes is much smaller than that along the CEU genomes, and recombination activity in the UK10K genomes is also much less concentrated. The same phenomena were also observed when comparing UK10K with its two subsets with 200 and 400 genomes. In all cases, analyses of a larger number of genomes result in a more precise estimation of recombination rate and a less concentrated recombination activity with fewer recombination hotpots identified. Generally, UK10K recombination hotspots are about 2.93-14.25 times fewer than that identified in previous studies. By comparing the recombination hotspots of UK10K and its subsets, we found that the false inference of population-specific recombination hotspots could be as high as 75.86% if the number of sampled genomes is not super large. The results suggest that the uncertainty of estimated recombination rate is substantial when sample size is not super large, and more attention should be paid to accurate identification of recombination hotspots, especially population-specific recombination hotspots.Author summaryWe applied FastEPRR, an artificial intelligence method to estimate recombination rates in the UK10K data set with 7,562 genomes and established the most accurate human genetic map. By comparing with other human genetic maps, we found that analyses of a larger number of genomes result in a more precise estimation of recombination rate and a less concentrated recombination activity with fewer recombination hotpots identified. The false inference of population-specific recombination hotspots could be substantial if the number of sampled genomes is not super large.

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

10.1101/016972 ◽

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.

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