Negative heterosis for meiotic recombination rate in spermatocytes of the domestic chicken Gallus gallus

Benefits and costs of meiotic recombination are a matter of discussion. Because recombination breaks allele combinations already tested by natural selection and generates new ones of unpredictable fitness, a high recombination rate is generally beneficial for the populations living in a fluctuating or a rapidly changing environment and costly in a stable environment. Besides genetic benefits and costs, there are cytological effects of recombination, both positive and negative. Recombination is necessary for chromosome synapsis and segregation. However, it involves a massive generation of double-strand DNA breaks, erroneous repair of which may lead to germ cell death or various mutations and chromosome rearrangements. Thus, the benefits of recombination (generation of new allele combinations) would prevail over its costs (occurrence of deleterious mutations) as long as the population remains sufficiently heterogeneous. Using immunolocalization of MLH1, a mismatch repair protein, at the synaptonemal complexes, we examined the number and distribution of recombination nodules in spermatocytes of two chicken breeds with high (Pervomai) and low (Russian Crested) recombination rates and their F1 hybrids and backcrosses. We detected negative heterosis for recombination rate in the F1 hybrids. Backcrosses to the Pervomai breed were rather homogenous and showed an intermediate recombination rate. The differences in overall recombination rate between the breeds, hybrids and backcrosses were mainly determined by the differences in the crossing over number in the seven largest macrochromosomes. The decrease in recombination rate in F1 is probably determined by difficulties in homology matching between the DNA sequences of genetically divergent breeds. The suppression of recombination in the hybrids may impede gene flow between parapatric populations and therefore accelerate their genetic divergence.

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Immunocytological Analysis of Meiotic Recombination in the Gray Goose (Anser anser)

Cytogenetic and Genome Research ◽

10.1159/000458741 ◽

2017 ◽

Vol 151 (1) ◽

pp. 27-35 ◽

Cited By ~ 9

Author(s):

Anna A. Torgasheva ◽

Pavel M. Borodin

Keyword(s):

Recombination Rate ◽

Interspecific Variation ◽

Male Meiosis ◽

Recombination Rates ◽

Anser Anser ◽

Recombination Nodules ◽

Repair Protein ◽

Protein Marking ◽

Mlh1 Foci ◽

Mismatch Repair Protein

Studies on mammals demonstrate wide interspecific variation in the number and distribution of recombination events along chromosomes. Birds represent an interesting model group for comparative analysis of cytological and ecological drivers of recombination rate evolution. Yet, data on variation in recombination rates in birds are limited to a dozen of species. In this study, we used immunolocalization of MLH1, a mismatch repair protein marking mature recombination nodules, to estimate the overall recombination rate and distribution of crossovers along macrochromosomes in female and male meiosis of the gray goose (Anser anser). The average number of MLH1 foci was significantly higher in oocytes than in spermatocytes (73.6 ± 7.8 and 58.9 ± 7.6, respectively). MLH1 foci distribution along individual macrobivalents showed subtelomeric peaks, which were more pronounced in males. Analysis of distances between neighboring MLH1 foci on macrobivalents revealed stronger crossover interference in male meiosis. These data create a framework for future genetic and physical mapping of the gray goose.

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Male Meiotic Recombination in the Steppe Agama, Trapelus sanguinolentus (Agamidae, Iguania, Reptilia)

Cytogenetic and Genome Research ◽

10.1159/000496078 ◽

2019 ◽

Vol 157 (1-2) ◽

pp. 107-114 ◽

Cited By ~ 3

Author(s):

Artem P. Lisachov ◽

Katerina V. Tishakova ◽

Yakov A. Tsepilov ◽

Pavel M. Borodin

Keyword(s):

Meiotic Recombination ◽

Mammalian Species ◽

Recombination Rates ◽

Mlh1 Focus ◽

Closely Related Species ◽

Lateral Element ◽

Recombination Nodules ◽

Repair Protein ◽

Mlh1 Foci ◽

Mismatch Repair Protein

Meiotic recombination rates and patterns of crossover distributions along the chromosomes vary considerably even between closely related species. The adaptive significance of these differences is still unclear due to the paucity of empirical data. Most data on recombination come from mammalian species, while other vertebrate clades are poorly explored. Using immunolocalization of the protein of the lateral element of the synaptonemal complex (SYCP3) and the mismatch-repair protein MLH1, which marks mature recombination nodules, we analyzed recombination rates and crossover distribution in meiotic prophase chromosomes of the steppe agama (Trapelus sanguinolentus, Agamidae, Acrodonta, Iguania) and compared them with data obtained for the genus Anolis (Dactyloidae, Pleurodonta, Iguania). We found that, despite a smaller genome size, the total SC length and the MLH1 focus number per cell are much higher in the agama than in the anoles. The distributions of the MLH1 foci in the agama are multimodal in larger chromosomes and bimodal in smaller chromosomes without a significant centromere effect, resembling the patterns known for birds. A possible relationship between karyotype remodeling and the evolution of recombination in Iguania is discussed.

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Fine-Structure Mapping of Meiosis-Specific Double-Strand DNA Breaks at a Recombination Hotspot Associated With an Insertion of Telomeric Sequences Upstream of the HIS4 Locus in Yeast

Genetics ◽

10.1093/genetics/143.3.1115 ◽

1996 ◽

Vol 143 (3) ◽

pp. 1115-1125 ◽

Cited By ~ 3

Author(s):

Fei Xu ◽

Thomas D Petes

Keyword(s):

Meiotic Recombination ◽

Hydroxyl Groups ◽

Sequence Specificity ◽

Structure Mapping ◽

Dna Breaks ◽

Exonuclease Iii ◽

Recombination Hotspot ◽

Telomeric Sequences ◽

Double Strand Dna Breaks ◽

Double Strand Dna

Abstract Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upstream of HIS4. We found that the breaks have no obvious sequence specificity and localize to a region of ~50 bp adjacent to the telomeric insertion. By mapping the breaks and by studies of the exonuclease III sensitivity of the broken ends, we conclude that most of the broken DNA molecules have blunt ends with 3′-hydroxyl groups.

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Competition Between Adjacent Meiotic Recombination Hotspots in the Yeast Saccharomyces cerevisiae

Genetics ◽

10.1093/genetics/145.3.661 ◽

1997 ◽

Vol 145 (3) ◽

pp. 661-670 ◽

Cited By ~ 1

Author(s):

Qing-Qing Fan ◽

Fei Xu ◽

Michael A White ◽

Thomas D Petes

Keyword(s):

Saccharomyces Cerevisiae ◽

Meiotic Recombination ◽

Telomeric Sequence ◽

Coding Region ◽

Dna Breaks ◽

Local Formation ◽

Yeast Saccharomyces Cerevisiae ◽

Recombination Hotspots ◽

Double Strand Dna Breaks ◽

His4 Gene

In a wild-type strain of Saccharomyces cerevisiae, a hotspot for meiotic recombination is located upstream of the HIS4 gene. An insertion of a 49-bp telomeric sequence into the coding region of HIS4 strongly stimulates meiotic recombination and the local formation of meiosis-specific double-strand DNA breaks (DSBs). When strains are constructed in which both hotspots are heterozygous, hotspot activity is substantially less when the hotspots are on the same chromosome than when they are on opposite chromosomes.

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Changes in protein composition of meiotic nodules during mammalian meiosis

Journal of Cell Science ◽

10.1242/jcs.111.4.413 ◽

1998 ◽

Vol 111 (4) ◽

pp. 413-423 ◽

Cited By ~ 13

Author(s):

A.W. Plug ◽

A.H. Peters ◽

K.S. Keegan ◽

M.F. Hoekstra ◽

P. de Boer ◽

...

Keyword(s):

Dna Sequences ◽

Protein A ◽

Reca Protein ◽

Protein Composition ◽

Homologous Chromosomes ◽

E Coli ◽

Recombination Nodules ◽

Chromosome Synapsis ◽

Repair Protein ◽

Mismatch Repair Protein

Homologous chromosome synapsis and meiotic recombination are facilitated by several meiosis-specific structures: the synaptonemal complex (SC), and two types of meiotic nodules: (1) early meiotic nodules (MNs), also called zygotene nodules or early recombination nodules, and (2) late recombination nodules (RNs). The former are thought to be nucleoprotein complexes involved in the check for homology preceding, or accompanying synapsis, while the latter have been shown to be involved in reciprocal recombination. We have examined by immunocytochemistry the meiotic localization of a series of proteins at sites along the asynapsed axial elements prior to homologous synapsis and at sites along the SCs following synapsis. Several of the proteins examined have been implicated in repair/recombination and include RAD51, a mammalian homolog of the Escherichia coli RecA protein; Replication Protein-A (RPA), a single-strand DNA binding protein; and MLH1, a mismatch repair protein which is a homolog of the E. coli MutL protein. In addition two proteins were examined that have been implicated in meiotic checkpoints: ATM, the protein mutated in the human disease Ataxia Telangiectasia, and ATR, another member of the same family of PIK kinases. We present evidence that these proteins are all components of meiotic nodules and document changes in protein composition of these structures during zygonema and pachynema of meiotic prophase in mouse spermatocytes. These studies support the supposition that a subset of MNs are converted into RNs. However, our data also demonstrate changes in protein composition within the context of early MNs, suggesting a differentiation of these nodules during the process of synapsis. The same changes in protein composition occurred on both the normal X axis, which has no homologous pairing partner in spermatocytes, and on the axes of aberrant chromosomes that nonhomologously synapse during synaptic adjustment. These findings suggest that DNA sequences associated with MNs still must undergo an obligatory processing, even in the absence of interactions between homologous chromosomes.

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A missense in HSF2BP causing Primary Ovarian Insufficiency affects meiotic recombination by its novel interactor C19ORF57/MIDAP

10.1101/2020.03.05.978007 ◽

2020 ◽

Cited By ~ 1

Author(s):

Natalia Felipe-Medina ◽

Sandrine Caburet ◽

Fernando Sánchez-Sáez ◽

Yazmine B. Condezo ◽

Dirk de Rooij ◽

...

Keyword(s):

Missense Variant ◽

Primary Ovarian Insufficiency ◽

Dna Breaks ◽

Ovarian Insufficiency ◽

Knock Out ◽

Recombination Nodules ◽

Meiotic Gene ◽

Double Strand Dna Breaks ◽

Gene Functional Analysis

AbstractPrimary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with 3 cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse, compared to a new HSF2BP knock-out mouse showed that it behaves as a hypomorphic allele. HSF2BP-S167L females show reduced fertility with small litter sizes. To obtain mechanistic insights, we identified C19ORF57/MIDAP as a strong interactor and stabilizer of HSF2BP by forming a higher-order macromolecular structure involving BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L mutation showed a strongly decreased expression of both MIDAP and HSF2BP at the recombination nodules. Although HSF2BP-S167L does not affect heterodimerization between HSF2BP and MIDAP, it promotes a lower expression of both proteins and a less proficient activity in replacing RPA by the recombinases RAD51/DMC1, thus leading to a lower frequency of cross-overs. Our results provide insights into the molecular mechanism of two novel actors of meiosis underlying non-syndromic ovarian insufficiency.SummaryFelipe-Medina et al. describe a missense variant in the meiotic gene HSF2BP in a consanguineous family with Premature Ovarian Insufficiency, and characterize it as an hypormorphic allele, that in vivo impairs its dimerization with a novel meiotic actor, MIDAP/ C19ORF57, and affect recombination at double-strand DNA breaks.

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Caenorhabditis elegans DSB-3 reveals conservation and divergence among protein complexes promoting meiotic double-strand breaks

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2109306118 ◽

2021 ◽

Vol 118 (33) ◽

pp. e2109306118

Author(s):

Albert W. Hinman ◽

Hsin-Yi Yeh ◽

Baptiste Roelens ◽

Kei Yamaya ◽

Alexander Woglar ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Meiotic Recombination ◽

Protein Complexes ◽

Meiotic Chromosome ◽

Structured Illumination ◽

Dna Breaks ◽

Structured Illumination Microscopy ◽

Strand Breaks ◽

Double Strand Dna Breaks ◽

Essential Components

Meiotic recombination plays dual roles in the evolution and stable inheritance of genomes: Recombination promotes genetic diversity by reassorting variants, and it establishes temporary connections between pairs of homologous chromosomes that ensure their future segregation. Meiotic recombination is initiated by generation of double-strand DNA breaks (DSBs) by the conserved topoisomerase-like protein Spo11. Despite strong conservation of Spo11 across eukaryotic kingdoms, auxiliary complexes that interact with Spo11 complexes to promote DSB formation are poorly conserved. Here, we identify DSB-3 as a DSB-promoting protein in the nematode Caenorhabditis elegans. Mutants lacking DSB-3 are proficient for homolog pairing and synapsis but fail to form crossovers. Lack of crossovers in dsb-3 mutants reflects a requirement for DSB-3 in meiotic DSB formation. DSB-3 concentrates in meiotic nuclei with timing similar to DSB-1 and DSB-2 (predicted homologs of yeast/mammalian Rec114/REC114), and DSB-1, DSB-2, and DSB-3 are interdependent for this localization. Bioinformatics analysis and interactions among the DSB proteins support the identity of DSB-3 as a homolog of MEI4 in conserved DSB-promoting complexes. This identification is reinforced by colocalization of pairwise combinations of DSB-1, DSB-2, and DSB-3 foci in structured illumination microscopy images of spread nuclei. However, unlike yeast Rec114, DSB-1 can interact directly with SPO-11, and in contrast to mouse REC114 and MEI4, DSB-1, DSB-2, and DSB-3 are not concentrated predominantly at meiotic chromosome axes. We speculate that variations in the meiotic program that have coevolved with distinct reproductive strategies in diverse organisms may contribute to and/or enable diversification of essential components of the meiotic machinery.

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Role of cis, trans, and inbreeding effects on meiotic recombination in Saccharomyces cerevisiae

10.1101/361428 ◽

2018 ◽

Author(s):

Xavier Raffoux ◽

Mickael Bourge ◽

Fabrice Dumas ◽

Olivier C. Martin ◽

Matthieu Falque

Keyword(s):

Saccharomyces Cerevisiae ◽

High Throughput ◽

Meiotic Recombination ◽

Recombination Rate ◽

Combining Ability ◽

Sequence Similarity ◽

Genetic Material ◽

Recombination Rates ◽

Important Species ◽

High Throughput Method

ABSTRACTMeiotic recombination is a major driver of genome evolution by creating new genetic combinations. To probe the factors driving variability of meiotic recombination, we used a high-throughput method to measure recombination rates in 26 S. cerevisiae strains from different geographic origins and habitats. Fourteen intervals were monitored for each strain, covering chromosomes VI and XI entirely, and part of chromosome I. We found an average number of crossovers per chromosome ranging between 1.0 and 9.5 across strains (“domesticated” or not), which is higher than the average between 0.5 and 1.5 found in most organisms. In the different intervals analyzed, recombination showed up to 9-fold variation across strains but global recombination landscapes along chromosomes varied less. We also built an incomplete diallel experiment to measure recombination rates in one region of chromosome XI in 10 different crosses involving five parental strains. Our overall results indicate that recombination rate is increasingly positively correlated with sequence similarity between homologs (i) in DSB rich regions within intervals, (ii) in entire intervals, and (iii) at the whole genome scale. Therefore, these correlations cannot be explained by cis-effects only. In addition, by using a quantitative genetics analysis, we identified an inbreeding effect that reduces recombination rate in homozygous genotypes while other interaction effects (specific combining ability) or additive effects (general combining ability) are found to be weak. Finally, we measured significant crossover interference in some strains, and interference intensity was positively correlated with crossover number.Author SummaryMeiosis is a key process for sexually reproducing organisms by producing gametes with a halved set of genetic material. An essential step of meiosis is the formation of crossovers which are reciprocal exchanges of genetic material between chromosomes inherited from both parents. Crossovers ensure proper chromosome segregation and thus viable gametes. They also create novel genetic diversity which contributes to evolution and permits genetic improvement of agriculturally important species. Most living organisms produce between one and three crossovers per chromosome, and tight regulatory mechanisms control the number of crossovers and their distribution along chromosomes. In spite of their potential importance for biotechnological applications, such mechanisms are still poorly understood.Using a high throughput method based on fluorescent markers, we investigated the diversity of recombination in the budding yeast Saccharomyces cerevisiae. We observed up to 9-fold differences in numbers of crossovers across hybrids obtained by crossing different strains with a common tester, and this variation was correlated with the degree of DNA sequence similarity between homologous chromosomes. By also investigating homozygotes, we conclude that on the one hand too much sequence divergence impairs recombination in distantly-related hybrids, and on the other hand complete homozygosity is also associated with lower numbers of crossovers.

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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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Mer2 binds directly to both nucleosomes and axial proteins as the keystone of meiotic recombination

10.1101/2020.07.30.228908 ◽

2020 ◽

Author(s):

Dorota Rousova ◽

Saskia K. Funk ◽

Heidi Reichle ◽

John R. Weir

Keyword(s):

Sexual Reproduction ◽

Meiotic Recombination ◽

Dna Breaks ◽

Homologous Chromosomes ◽

Protein Biochemistry ◽

Double Strand Dna Breaks ◽

Domain Protein ◽

Meiosis I ◽

Double Strand Dna

One of the defining features of sexual reproduction is the recombination events that take place during meiosis I. Recombination is both evolutionarily advantageous, but also mechanistically necessary to form the crossovers that link homologous chromosomes. Meiotic recombination is initiated through the placement of programmed double-strand DNA breaks (DSBs) mediated by the protein Spo11. The timing, number, and physical placement of DSBs are carefully controlled through a variety of protein machinery. Previous work has implicated Mer2(IHO1 in mammals) to be involved in both the placement of breaks, and their timing. In this study we use a combination of protein biochemistry and biophysics to extensively characterise various roles of the Mer2. We gain further insights into the details of Mer2 interaction with the PHD protein Spp1, reveal that Mer2 is a novel nucleosome binder, and suggest how Mer2’s interaction with the HORMA domain protein Hop1 (HORMAD1/2 in mammals) is controlled.

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