Recombination Cold Spots Research Articles

A catalogue of recombination coldspots in interspecific tomato hybrids.

Increasing natural resistance and resilience in plants is key for ensuring food security within a changing climate. Breeders improve these traits by crossing cultivars with their wild relatives and introgressing specific alleles through meiotic recombination. However, some genomic regions are devoid of recombination especially in crosses between divergent genomes, limiting the combinations of desirable alleles. Here, we used pooled-pollen sequencing to build a map of recombinant and non-recombinant regions between tomato and five wild relatives commonly used for introgressive tomato breeding. We detected hybrid-specific recombination coldspots that underscore the role of structural variations in modifying recombination patterns and maintaining genetic linkage in interspecific crosses. Crossover regions and coldspots show strong association with specific TE superfamilies exhibiting differentially accessible chromatin between somatic and meiotic cells. About two-thirds of the genome are conserved coldspots, located mostly in the pericentromeres and enriched with retrotransposons. The coldspots also harbor genes associated with agronomic traits and stress resistance, revealing undesired consequences of linkage drag and possible barriers to breeding. We presented examples of linkage drag that can potentially be resolved by pairing tomato with other wild species. Overall, this catalogue will help breeders better understand crossover localization and make informed decisions on generating new tomato varieties.

Exploration of Genome-Wide Recombination Rate Variation Patterns at Different Scales in Pigs.

Meiotic recombination is a prevalent process in eukaryotic sexual reproduction organisms that plays key roles in genetic diversity, breed selection, and species evolution. However, the recombination events differ across breeds and even within breeds. In this study, we initially computed large-scale population recombination rates of both sexes using approximately 52 K SNP genotypes in a total of 3279 pigs from four different Chinese and Western breeds. We then constructed a high-resolution historical recombination map using approximately 16 million SNPs from a sample of unrelated individuals. Comparative analysis of porcine recombination events from different breeds and at different resolutions revealed the following observations: Firstly, the 1Mb-scale pig recombination maps of the same sex are moderately conserved among different breeds, with the similarity of recombination events between Western pigs and Chinese indigenous pigs being lower than within their respective groups. Secondly, we identified 3861 recombination hotspots in the genome and observed medium- to high-level correlation between historical recombination rates (0.542~0.683) and estimates of meiotic recombination rates. Third, we observed that recombination hotspots are significantly far from the transcription start sites of pig genes, and the silico-predicted PRDM9 zinc finger domain DNA recognition motif is significantly enriched in the regions of recombination hotspots compared to recombination coldspots, highlighting the potential role of PRDM9 in regulating recombination hotspots in pigs. Our study analyzed the variation patterns of the pig recombination map at broad and fine scales, providing a valuable reference for genomic selection breeding and laying a crucial foundation for further understanding the molecular mechanisms of pig genome recombination.

The fine-scale recombination rate variation and associations with genomic features in a butterfly.

Recombination is a key molecular mechanism that has profound implications on both micro- and macroevolutionary processes. However, the determinants of recombination rate variation in holocentric organisms are poorly understood, in particular in Lepidoptera (moths and butterflies). The wood white butterfly (Leptidea sinapis) shows considerable intraspecific variation in chromosome numbers and is a suitable system for studying regional recombination rate variation and its potential molecular underpinnings. Here, we developed a large whole-genome resequencing data set from a population of wood whites to obtain high-resolution recombination maps using linkage disequilibrium information. The analyses revealed that larger chromosomes had a bimodal recombination landscape, potentially caused by interference between simultaneous chiasmata. The recombination rate was significantly lower in subtelomeric regions, with exceptions associated with segregating chromosome rearrangements, showing that fissions and fusions can have considerable effects on the recombination landscape. There was no association between the inferred recombination rate and base composition, supporting a limited influence of GC-biased gene conversion in butterflies. We found significant but variable associations between the recombination rate and the density of different classes of transposable elements, most notably a significant enrichment of short interspersed nucleotide elements in genomic regions with higher recombination rate. Finally, the analyses unveiled significant enrichment of genes involved in farnesyltranstransferase activity in recombination coldspots, potentially indicating that expression of transferases can inhibit formation of chiasmata during meiotic division. Our results provide novel information about recombination rate variation in holocentric organisms and have particular implications for forthcoming research in population genetics, molecular/genome evolution, and speciation.

Genetic architectures of postmating isolation and morphology of two highly diverged rockfishes (genus Sebastes).

Postmating isolation is thought to be an important driver of the late stages of speciation. However, relatively little is empirically known about the process compared with other isolating mechanisms that drive the early stages of speciation, especially in non-model organisms. We characterized the genetic architecture of postmating isolation between 2 rockfishes, Sebastes schlegelii and S. trivittatus, whose reproductive isolation is complete. We examined transmission ratio distortion (TRD) patterns of genetic markers in 2 reciprocal backcross populations. Markers showing either of the 2 types of TRD was widespread across the genome, with some of the distorted markers forming extensive clusters around the recombination coldspots. These suggest that the postmating isolation effectively prevents gene flow across the genome and the recombination landscape contributes to the genetic architecture. Comparisons between 2 backcross families and 2 developmental stages showed little similarity in the distorted markers, suggesting asymmetry and stage specificity of the isolation. This may be due to hybrid incompatibility involving maternal factors or extrinsic selection. The lack of sex-ratio distortion in the mapping families suggested that Haldane's rule in terms of hybrid inviability does not hold. Additionally, quantitative trait loci (QTL) mapping detected significant QTLs for sex and the morphological traits relevant to speciation and convergence of rockfishes, including body coloration. Genes in the melanocortin system, including agouti-signaling protein 1 (asip1) and melanocortin 1 receptor (mc1r), might underlie the horizontal and vertical color patterns on the body, respectively. These findings constitute an essential step toward a comprehensive understanding of speciation and morphological diversification of rockfishes.

Genome-wide recombination variation in biparental segregating and reciprocal backcross populations provides information for introgression breeding in Brassica napus

Variation in patterns of recombination in plant genomes provides information about species evolution, genetic diversity and crop improvement. We investigated meiotic crossovers generated in biparental segregating and reciprocal backcross populations of the allopolyploid genome of rapeseed (Brassica napus) (AACC, 2n = 38). A structured set of 1445 intercrossed lines was derived from two homozygous de novo genome-assembled parents that represented the major genetic clusters of semi-winter Chinese and winter European rapeseeds, and was used to increase QTL resolution and achieve genomic reciprocal introgression. A high-density genetic map constructed with 6161 genetic bins and anchored centromere regions was used to establish the pattern of recombination variation in each chromosome. Around 93% of the genome contained crossovers at a mean rate of 3.8 cM Mb−1, with the remaining 7% attributed to centromeres or low marker density. Recombination hotspots predominated in the A genome, including two-thirds of those associated with breeding introgression from B. rapa. Genetic background might affect recombination variation. Introgression of genetic diversity from European winter to Chinese semi-winter rapeseed showed an increase in crossover rate under the semi-winter environment. Evidence for an elevated recombination rate having historically contributed to selective trait improvement includes accumulation of favorable alleles for seed oil content on hotspots of chromosome A10. Conversely, strong artificial selection may affect recombination rate variation, as appears to be the case with a coldspot resulting from strong selection for glucosinolate alleles on A09. But the cold region would be promptly reactivated by crossing design indicated by the pedigree analysis. Knowledge of recombination hotspots and coldspots associated with QTL for 22 traits can guide selection strategies for introgression breeding between the two gene pools. These results and rich genomic resources broaden our understanding of recombination behavior in allopolyploids and may advance rapeseed genetic improvement.

Turning coldspots into hotspots: targeted recruitment of axis protein Hop1 stimulates meiotic recombination in Saccharomyces cerevisiae.

The DNA double-strand breaks that initiate meiotic recombination are formed in the context of the meiotic chromosome axis, which in Saccharomyces cerevisiae contains a meiosis-specific cohesin isoform and the meiosis-specific proteins Hop1 and Red1. Hop1 and Red1 are important for double-strand break formation; double-strand break levels are reduced in their absence and their levels, which vary along the lengths of chromosomes, are positively correlated with double-strand break levels. How axis protein levels influence double-strand break formation and recombination remains unclear. To address this question, we developed a novel approach that uses a bacterial ParB-parS partition system to recruit axis proteins at high levels to inserts at recombination coldspots where Hop1 and Red1 levels are normally low. Recruiting Hop1 markedly increased double-strand breaks and homologous recombination at target loci, to levels equivalent to those observed at endogenous recombination hotspots. This local increase in double-strand breaks did not require Red1 or the meiosis-specific cohesin component Rec8, indicating that, of the axis proteins, Hop1 is sufficient to promote double-strand break formation. However, while most crossovers at endogenous recombination hotspots are formed by the meiosis-specific MutLγ resolvase, crossovers that formed at an insert locus were only modestly reduced in the absence of MutLγ, regardless of whether or not Hop1 was recruited to that locus. Thus, while local Hop1 levels determine local double-strand break levels, the recombination pathways that repair these breaks can be determined by other factors, raising the intriguing possibility that different recombination pathways operate in different parts of the genome.

Three problems in the genetics of speciation by selection

Speciation is the process by which barriers to gene flow evolve between populations. Although we now know that speciation is largely driven by natural selection, knowledge of the agents of selection and the genetic and genomic mechanisms that facilitate divergence is required for a satisfactory theory of speciation. In this essay, we highlight three advances/problems in our understanding of speciation that have arisen from studies of the genes and genomic regions that underlie the evolution of reproductive isolation. First, we describe how the identification of “speciation” genes makes it possible to identify the agents of selection causing the evolution of reproductive isolation, while also noting that the link between the genetics of phenotypic divergence and intrinsic postzygotic reproductive barriers remains tenuous. Second, we discuss the important role of recombination suppressors in facilitating speciation with gene flow, but point out that the means and timing by which reproductive barriers become associated with recombination cold spots remains uncertain. Third, we establish the importance of ancient genetic variation in speciation, although we argue that the focus of speciation studies on evolutionarily young groups may bias conclusions in favor of ancient variation relative to new mutations.

Editorial 2022

Editorial 2022

Identification and candidate gene mining of HvSS1, a novel qualitative locus on chromosome 6H, regulating the uppermost internode elongation in barley (Hordeum vulgare L.).

A novel qualitative locus regulating the uppermost internode elongation of barley was identified and mapped on 6H, and the candidate gene mining was performed by employing various barley genomic resources. The stem of grass crops, such as barley and wheat, is composed of several interconnected internodes. The extent of elongation of these internodes determines stem height, and hence lodging, canopy architecture, and grain yield. The uppermost internode (UI) is the last internode to elongate. Its elongation contributes largely to stem height and facilitates spike exsertion, which is crucial for final grain yield. Despite the molecular mechanism underlying regulation of UI elongation was extensively investigated in rice, little is known in barley. In this study, we characterized a barley spontaneous mutant, Sheathed Spike 1 (SS1), showing significantly shortened UI and sheathed spike (SS). The extension of UI parenchyma cell in SS1 was significantly suppressed. Exogenous hormone treatments and RNA-seq analysis indicated that the suppression of UI elongationis possibly related to insufficient contentof endogenous bioactive gibberellin. Genetic analysis showed that SS1 is possibly controlled by a qualitative dominant nuclear factor. Bulked segregant analysis and further molecular marker mapping identified a novel major locus, HvSS1, in a recombination cold spot expanding 173.44-396.33Mb on chromosome 6H. The candidate gene mining was further conducted by analyzing sequence differences, spatiotemporal expression patterns, and variant distributions of genes in the candidate interval by employing various barley genomic resources of worldwide collections of barley accessions. This study made insight into genetic control of UI elongation in barley and laid a solid foundation for further gene cloning and functional characterization. The results obtained here also provided valuable information for similar research in wheat.

Genomic Structure of Hstx2 Modifier of Prdm9-Dependent Hybrid Male Sterility in Mice.

F1 hybrids between mouse inbred strains PWD and C57BL/6 represent the most thoroughly genetically defined model of hybrid sterility in vertebrates. Hybrid male sterility can be fully reconstituted from three components of this model, the Prdm9 gene, intersubspecific homeology of Mus musculus musculus and Mus musculus domesticus autosomes, and the X-linked Hstx2 locus. Hstx2 modulates the extent of Prdm9-dependent meiotic arrest and harbors two additional factors responsible for intersubspecific introgression-induced oligospermia (Hstx1) and meiotic recombination rate (Meir1). To facilitate positional cloning and to overcome the recombination suppression within the 4.3 Mb encompassing the Hstx2 locus, we designed Hstx2-CRISPR and SPO11/Cas9 transgenes aimed to induce DNA double-strand breaks specifically within the Hstx2 locus. The resulting recombinant reduced the Hstx2 locus to 2.70 Mb (chromosome X: 66.51-69.21 Mb). The newly defined Hstx2 locus still operates as the major X-linked factor of the F1 hybrid sterility, and controls meiotic chromosome synapsis and meiotic recombination rate. Despite extensive further crosses, the 2.70 Mb Hstx2 interval behaved as a recombination cold spot with reduced PRDM9-mediated H3K4me3 hotspots and absence of DMC1-defined DNA double-strand-break hotspots. To search for structural anomalies as a possible cause of recombination suppression, we used optical mapping and observed high incidence of subspecies-specific structural variants along the X chromosome, with a striking copy number polymorphism of the microRNA Mir465 cluster. This observation together with the absence of a strong sterility phenotype in Fmr1 neighbor (Fmr1nb) null mutants support the role of microRNA as a likely candidate for Hstx2.

Recombination-Aware Phylogenomics Reveals the Structured Genomic Landscape of Hybridizing Cat Species.

Current phylogenomic approaches implicitly assume that the predominant phylogenetic signal within a genome reflects the true evolutionary history of organisms, without assessing the confounding effects of postspeciation gene flow that can produce a mosaic of phylogenetic signals that interact with recombinational variation. Here, we tested the validity of this assumption with a phylogenomic analysis of 27 species of the cat family, assessing local effects of recombination rate on species tree inference and divergence time estimation across their genomes. We found that the prevailing phylogenetic signal within the autosomes is not always representative of the most probable speciation history, due to ancient hybridization throughout felid evolution. Instead, phylogenetic signal was concentrated within regions of low recombination, and notably enriched within large X chromosome recombination cold spots that exhibited recurrent patterns of strong genetic differentiation and selective sweeps across mammalian orders. By contrast, regions of high recombination were enriched for signatures of ancient gene flow, and these sequences inflated crown-lineage divergence times by ∼40%. We conclude that existing phylogenomic approaches to infer the Tree of Life may be highly misleading without considering the genomic architecture of phylogenetic signal relative to recombination rate and its interplay with historical hybridization.

Cloning of a COBL gene determining brittleness in diploid wheat using a MapRseq approach

Plant tissue brittleness is related to cellular structure and lodging. MED0031 is a mutant identified previously from ethyl methane sulfonate treatment of diploid wheat accession TA2726, showing brittleness in both stem and leaf. In microscopic and histological observations, the mutant was found to have less large vascular bundles per unit area, a thinner sclerenchyma cell wall, and a broader parenchyma, compared with the wild type. The mutated gene, TmBr1, was mapped to a 0.056 cM interval on chromosome 5Am. This gene was cloned using a MapRseq approach that searched the candidate gene through combination of the prior target gene mapping information with SNP calling and discovery of differentially expressed genes from RNA_seq data of the wild type and a BC3F2 bulk showing the mutant phenotype. TmBr1 encodes a COBL protein and a nonsense mutation within the region coding for the conserved COBRA domain caused premature translation termination. Introduction of TmBr1 to Arabidopsis AtCOBL4 mutant rescued the phenotype, demonstrating their functional conservation. Apart from the effect on cellulose content, the TmBr1 mutation might modulate synthesis of noncellulosic polysaccharide pectin as well. Application of the MapRseq approach to isolation of genes present in recombination cold spots and complicated genomes was discussed.

A common genomic code for chromatin architecture and recombination landscape.

Recent findings established a link between DNA sequence composition and interphase chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse conformation capture and recombination rate data to study the relationship between chromatin architecture and recombination landscape of human and mouse genomes. The results reveal that: (1) low recombination domains and blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhoods; (2) double strand break (DSB) and recombination frequencies increase in the short loops of GC-rich TADs, whereas recombination cold spots are typical of LADs and (3) the binding and loading of proteins, which are critical for DSB and meiotic recombination (SPO11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated with compositional and epigenetic features (genomic code) that influence DNA stiffness/flexibility and appear to be similar to those guiding the chromatin architecture in the interphase nucleus of pre-leptotene cells.

Forward genetics using radiation hybrids (deletion mutants) in plants

Identification of the QTL/genes associated with traits of interest determines the successful application of those genes for crop improvement. After identification of QTL, fine mapping and cloning of important QTL can also enhance our understanding of the genetic structure of the underlying genes responsible for the phenotypic variation. Genetic or recombination mapping is the most common approach used to identify, map and clone QTL or genes in plants. However, genetic mapping approach for fine mapping or map-based cloning is associated with many drawbacks including the need of developing a homogenous and large population, the availability of polymorphic markers, and the poor recombination in certain chromosomal regions. In this article, we describe an alternative approach, called radiation hybrid (RH) mapping, for forward genetic studies in plants. This approach has been extensively used in animal system and offer greater prospects for forward genetic studies in plants as well. The RH mapping uses radiation induced chromosomal breaks to map markers, and thus offers many advantages compared to traditionally used genetic mapping approach, particularly for loci located in recombination cold spots and for the traits which lack genetic diversity. Here, we reviewed the progress made in application of RH approach for forward genetics in plants.

IRSpot-Pse6NC: Identifying recombination spots in Saccharomyces cerevisiae by incorporating hexamer composition into general PseKNC.

Meiotic recombination caused by meiotic double-strand DNA breaks. In some regions the frequency of DNA recombination is relatively higher, while in other regions the frequency is lower: the former is usually called “recombination hotspot”, while the latter the “recombination coldspot”. Information of the hot and cold spots may provide important clues for understanding the mechanism of genome revolution. Therefore, it is important to accurately predict these spots. In this study, we rebuilt the benchmark dataset by unifying its samples with a same length (131 bp). Based on such a foundation and using SVM (Support Vector Machine) classifier, a new predictor called “iRSpot-Pse6NC” was developed by incorporating the key hexamer features into the general PseKNC (Pseudo K-tuple Nucleotide Composition) via the binomial distribution approach. It has been observed via rigorous cross-validations that the proposed predictor is superior to its counterparts in overall accuracy, stability, sensitivity and specificity. For the convenience of most experimental scientists, the web-server for iRSpot-Pse6NC has been established at http://lin-group.cn/server/iRSpot-Pse6NC, by which users can easily obtain their desired result without the need to go through the detailed mathematical equations involved.

IRSpotH-TNCPseAAC: Identifying Recombination Spots in Human by Using Pseudo Trinucleotide Composition With an Ensemble of Support Vector Machine Classifiers

Background: For the formation of human gametes, meiotic recombination is crucial. Meanwhile, it has played an important role in the process that generates genetic diversity for that it is a defining event in the formation of human sperm and eggs. However, the recombination isn't a random occurrence across a genome, it usually occurs in some genomic regions, the so-called “hotspots”, with higher probability, while in the so-called “coldspots” with lower probability. Research has shown that new combinations of genetic variations can be provided by recombination. Therefore, the useful insights for in-depth studying of the genome evolution process and the mechanism of recombination would be provided based on the information of the coldspots and hotspots. Currently, the recombination regions would be determined by experiments, but it's a tedious job, which generally requires precious instruments and takes a long time. So in the study the work is starting to be studied by computational predicting models to address the above problems. Method: In this paper, a new predictor, called ‘iRSpotH-TNCPseAAC’ was developed to identify the human recombination coldspots and hotspots. In the new discrete predictive model, a feature vector called ‘pseudo trinucleotide composition’ or PseTNC is proposed to formulate the given DNA segment with its sequence-order information as complete as possible. Results: In this study, based on the rigorous jackknife test the overall success rate obtained by iRSpotH- TNCPseAAC is higher than 93% in identifying human’s recombination spots, and with mean success rate is 76.07% of the concerned 18 chromosomes. It means that our predictor can become a useful complementary tool in this area. Not only that, the PseTNC method can be used to further explore many other DNA-related problems. Finally, a web- server called iRSpotH-TNCPseAAC, which has the advantages of easy operation and convenient for using, is built and freely accessible at http://www.jci-bioinfo.cn/iRSpotH-TNCPseAAC. Conclusion: To timely acquire the information of recombination spots in DNA sequence is very significant to make in-depth study on epigenetic inheritance and analyze human diseases. Furthermore, it will facilitate drug development. A certain conclusion is that the iRSpotH-TNCPseAAC predictor may become a very practical online predictive high throughput tools in identifying recombination spots. Keywords: Pseudo amino acid composition, support vector machine, web-server, iRSpotH-TNCPseAAC, meiosis, coldspots, hotspots.

Comparative High-Density Linkage Mapping Reveals Conserved Genome Structure but Variation in Levels of Heterochiasmy and Location of Recombination Cold Spots in the Common Frog.

By combining 7077 SNPs and 61 microsatellites, we present the first linkage map for some of the early diverged lineages of the common frog, Rana temporaria, and the densest linkage map to date for this species. We found high homology with the published linkage maps of the Eastern and Western lineages but with differences in the order of some markers. Homology was also strong with the genome of the Tibetan frog Nanorana parkeri and we found high synteny with the clawed frog Xenopus tropicalis. We confirmed marked heterochiasmy between sexes and detected nonrecombining regions in several groups of the male linkage map. Contrary to the expectations set by the male heterogamety of the common frog, we did not find male heterozygosity excess in the chromosome previously shown to be linked to sex determination. Finally, we found blocks of loci showing strong transmission ratio distortion. These distorted genomic regions might be related to genetic incompatibilities between the parental populations, and are promising candidates for further investigation into the genetic basis of speciation and adaptation in the common frog.

The phylogenetic and recombinational analysis of beak and feather disease virus Taiwan isolates.

Beak and feather disease virus (BFDV) is an avian circovirus, and it has a single-stranded DNA genome. It causes a fatal disease in parrots called psittacine beak and feather disease (PBFD). After screening of samples collected from Taiwan using PCR, complete genome sequences of isolates from 21 samples from various species of parrot were obtained. The nucleotide sequences of the replication-associated protein gene (rep) and the amino acid sequences of the replication-associated protein (Rep) were more conserved than the nucleotide sequences of the capsid protein gene (cp) and the amino acid sequences of the capsid protein (CP). In Bayesian phylogenetic analysis, the topology of the complete genome sequence was similar to that of the rep gene alone. Recombination events were identified in Taiwan isolates. Recombination hot spots were mainly located in the intergenic region between the 3' ends of the rep and cp genes and at the 5' end of the cp gene. The 5' end and the middle of the rep gene were found to be recombination cold spots. Despite the overall negative selection that was observed for the rep and cp genes, one and 18 positive selected sites were found for the rep and cp gene, respectively.

Recombination Hotspot/Coldspot Identification Combining Three Different Pseudocomponents via an Ensemble Learning Approach.

Recombination presents a nonuniform distribution across the genome. Genomic regions that present relatively higher frequencies of recombination are called hotspots while those with relatively lower frequencies of recombination are recombination coldspots. Therefore, the identification of hotspots/coldspots could provide useful information for the study of the mechanism of recombination. In this study, a new computational predictor called SVM-EL was proposed to identify hotspots/coldspots across the yeast genome. It combined Support Vector Machines (SVMs) and Ensemble Learning (EL) based on three features including basic kmer (Kmer), dinucleotide-based auto-cross covariance (DACC), and pseudo dinucleotide composition (PseDNC). These features are able to incorporate the nucleic acid composition and their order information into the predictor. The proposed SVM-EL achieves an accuracy of 82.89% on a widely used benchmark dataset, which outperforms some related methods.

Phylogenomic evidence for ancient hybridization in the genomes of living cats (Felidae).

Inter-species hybridization has been recently recognized as potentially common in wild animals, but the extent to which it shapes modern genomes is still poorly understood. Distinguishing historical hybridization events from other processes leading to phylogenetic discordance among different markers requires a well-resolved species tree that considers all modes of inheritance and overcomes systematic problems due to rapid lineage diversification by sampling large genomic character sets. Here, we assessed genome-wide phylogenetic variation across a diverse mammalian family, Felidae (cats). We combined genotypes from a genome-wide SNP array with additional autosomal, X- and Y-linked variants to sample ∼150 kb of nuclear sequence, in addition to complete mitochondrial genomes generated using light-coverage Illumina sequencing. We present the first robust felid time tree that accounts for unique maternal, paternal, and biparental evolutionary histories. Signatures of phylogenetic discordance were abundant in the genomes of modern cats, in many cases indicating hybridization as the most likely cause. Comparison of big cat whole-genome sequences revealed a substantial reduction of X-linked divergence times across several large recombination cold spots, which were highly enriched for signatures of selection-driven post-divergence hybridization between the ancestors of the snow leopard and lion lineages. These results highlight the mosaic origin of modern felid genomes and the influence of sex chromosomes and sex-biased dispersal in post-speciation gene flow. A complete resolution of the tree of life will require comprehensive genomic sampling of biparental and sex-limited genetic variation to identify and control for phylogenetic conflict caused by ancient admixture and sex-biased differences in genomic transmission.