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1.
Extremophiles ; 24(3): 433-446, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32296946

RESUMO

Glutamine synthetase is an essential enzyme in ammonium assimilation and glutamine biosynthesis. The Haloferax mediterranei genome has two other glnA-type genes (glnA2 and glnA3) in addition to the glutamine synthetase gene glnA. To determine whether the glnA2 and glnA3 genes can replace glnA in nitrogen metabolism, we generated deletion mutants of glnA. The glnA deletion mutants could not be generated in a medium without glutamine, and thus, glnA is an essential gene in H. mediterranei. The glnA deletion mutant was achieved by adding 40 mM glutamine to the selective medium. This conditional HM26-ΔglnA mutant was characterised with different approaches in the presence of distinct nitrogen sources and nitrogen starvation. Transcriptomic analysis was performed to compare the expression profiles of the strains HM26-ΔglnA and HM26 under different growth conditions. The glnA deletion did not affect the expression of glnA2, glnA3 and nitrogen assimilation genes under nitrogen starvation. Moreover, the results showed that glnA, glnA2 and glnA3 were not expressed under the same conditions. These results indicated that glnA is an essential gene for H. mediterranei and, therefore, glnA2 and glnA3 cannot replace glnA in the conditions analysed.


Assuntos
Haloferax mediterranei , Conversão Gênica , Glutamato-Amônia Ligase , Glutamina
2.
PLoS Genet ; 15(11): e1008493, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31703064

RESUMO

Genomic GC content varies widely among microbes for reasons unknown. While mutation bias partially explains this variation, prokaryotes near-universally have a higher GC content than predicted solely by this bias. Debate surrounds the relative importance of the remaining explanations of selection versus biased gene conversion favoring GC alleles. Some environments (e.g. soils) are associated with a high genomic GC content of their inhabitants, which implies that either high GC content is a selective adaptation to particular habitats, or that certain habitats favor increased rates of gene conversion. Here, we report a novel association between the presence of the non-homologous end joining DNA double-strand break repair pathway and GC content; this observation suggests that DNA damage may be a fundamental driver of GC content, leading in part to the many environmental patterns observed to-date. We discuss potential mechanisms accounting for the observed association, and provide preliminary evidence that sites experiencing higher rates of double-strand breaks are under selection for increased GC content relative to the genomic background.


Assuntos
Composição de Bases/genética , Evolução Molecular , Conversão Gênica/genética , Células Procarióticas , Quebras de DNA de Cadeia Dupla , Reparo do DNA por Junção de Extremidades/genética , Reparo do DNA/genética , Genoma/genética , Humanos
3.
Genes (Basel) ; 10(9)2019 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500388

RESUMO

Plant nucleotide-binding domain and leucine-rich repeat containing (NLR) genes provide some of the most extreme examples of polymorphism in eukaryotic genomes, rivalling even the vertebrate major histocompatibility complex. Surprisingly, this is also true in Arabidopsis thaliana, a predominantly selfing species with low heterozygosity. Here, we investigate how gene duplication and intergenic exchange contribute to this extraordinary variation. RPP8 is a three-locus system that is configured chromosomally as either a direct-repeat tandem duplication or as a single copy locus, plus a locus 2 Mb distant. We sequenced 48 RPP8 alleles from 37 accessions of A. thaliana and 12 RPP8 alleles from Arabidopsis lyrata to investigate the patterns of interlocus shared variation. The tandem duplicates display fixed differences and share less variation with each other than either shares with the distant paralog. A high level of shared polymorphism among alleles at one of the tandem duplicates, the single-copy locus and the distal locus, must involve both classical crossing over and intergenic gene conversion. Despite these polymorphism-enhancing mechanisms, the observed nucleotide diversity could not be replicated under neutral forward-in-time simulations. Only by adding balancing selection to the simulations do they approach the level of polymorphism observed at RPP8. In this NLR gene triad, genetic architecture, gene function and selection all combine to generate diversity.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Polimorfismo Genético , Evolução Molecular , Conversão Gênica , Duplicação Gênica
4.
Genomics Proteomics Bioinformatics ; 17(3): 305-310, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31437583

RESUMO

Published genomes frequently contain erroneous gene models that represent issues associated with identification of open reading frames, start sites, splice sites, and related structural features. The source of these inconsistencies is often traced back to integration across text file formats designed to describe long read alignments and predicted gene structures. In addition, the majority of gene prediction frameworks do not provide robust downstream filtering to remove problematic gene annotations, nor do they represent these annotations in a format consistent with current file standards. These frameworks also lack consideration for functional attributes, such as the presence or absence of protein domains that can be used for gene model validation. To provide oversight to the increasing number of published genome annotations, we present a software package, the Gene Filtering, Analysis, and Conversion (gFACs), to filter, analyze, and convert predicted gene models and alignments. The software operates across a wide range of alignment, analysis, and gene prediction files with a flexible framework for defining gene models with reliable structural and functional attributes. gFACs supports common downstream applications, including genome browsers, and generates extensive details on the filtering process, including distributions that can be visualized to further assess the proposed gene space. gFACs is freely available and implemented in Perl with support from BioPerl libraries at https://gitlab.com/PlantGenomicsLab/gFACs.


Assuntos
Conversão Gênica , Genoma , Genômica/métodos , Anotação de Sequência Molecular , Animais , Humanos , Fases de Leitura Aberta , Software , Especificidade da Espécie
5.
Nat Commun ; 10(1): 3900, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467277

RESUMO

During meiotic recombination, homologue-templated repair of programmed DNA double-strand breaks (DSBs) produces relatively few crossovers and many difficult-to-detect non-crossovers. By intercrossing two diverged mouse subspecies over five generations and deep-sequencing 119 offspring, we detect thousands of crossover and non-crossover events genome-wide with unprecedented power and spatial resolution. We find that both crossovers and non-crossovers are strongly depleted at DSB hotspots where the DSB-positioning protein PRDM9 fails to bind to the unbroken homologous chromosome, revealing that PRDM9 also functions to promote homologue-templated repair. Our results show that complex non-crossovers are much rarer in mice than humans, consistent with complex events arising from accumulated non-programmed DNA damage. Unexpectedly, we also find that GC-biased gene conversion is restricted to non-crossover tracts containing only one mismatch. These results demonstrate that local genetic diversity profoundly alters meiotic repair pathway decisions via at least two distinct mechanisms, impacting genome evolution and Prdm9-related hybrid infertility.


Assuntos
Quebras de DNA de Cadeia Dupla , Variação Genética , Recombinação Homóloga , Alelos , Animais , Proteínas de Ciclo Celular/genética , Cromossomos , Troca Genética , Dano ao DNA , Reparo de Erro de Pareamento de DNA , Feminino , Conversão Gênica , Histona-Lisina N-Metiltransferase/genética , Histonas/genética , Humanos , Hibridização Genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Genéticos , Proteínas de Ligação a Fosfato/genética , Polimorfismo de Nucleotídeo Único , Reparo de DNA por Recombinação
6.
Genetics ; 213(2): 665-683, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31371407

RESUMO

Loss of heterozygosity (LOH) is observed during vegetative growth and reproduction of diploid genotypes through mitotic crossovers, aneuploidy caused by nondisjunction, and gene conversion. We aimed to test the role that LOH plays during adaptation of two highly heterozygous Saccharomyces cerevisiae genotypes to multiple environments over a short time span in the laboratory. We hypothesized that adaptation would be observed through parallel LOH events across replicate populations. Using genome resequencing of 70 clones, we found that LOH was widespread with 5.2 LOH events per clone after ∼500 generations. The most common mode of LOH was gene conversion (51%) followed by crossing over consistent with either break-induced replication or double Holliday junction resolution. There was no evidence that LOH involved nondisjunction of whole chromosomes. We observed parallel LOH in both an environment-specific and environment-independent manner. LOH largely involved recombining existing variation between the parental genotypes, but also was observed after de novo, presumably beneficial, mutations occurred in the presence of canavanine, a toxic analog of arginine. One highly parallel LOH event involved the ENA salt efflux pump locus on chromosome IV, which showed repeated LOH to the allele from the European parent, an allele originally derived by introgression from S. paradoxus Using CRISPR-engineered LOH we showed that the fitness advantage provided by this single LOH event was 27%. Overall, we found extensive evidence that LOH could be adaptive and is likely to be a greater source of initial variation than de novo mutation for rapid evolution of diploid genotypes.


Assuntos
Cromossomos Fúngicos/genética , Evolução Clonal/genética , Perda de Heterozigosidade/genética , Saccharomyces cerevisiae/genética , Adaptação Fisiológica/genética , Alelos , Aneuploidia , Reparo do DNA/genética , Diploide , Conversão Gênica/genética , Heterozigoto , Recombinação Genética
7.
Mol Biol Evol ; 36(10): 2227-2237, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31362306

RESUMO

A key question in evolutionary biology concerns the relative importance of different sources of adaptive genetic variation, such as de novo mutations, standing variation, and introgressive hybridization. A corollary question concerns how allelic variants derived from these different sources may influence the molecular basis of phenotypic adaptation. Here, we use a protein-engineering approach to examine the phenotypic effect of putatively adaptive hemoglobin (Hb) mutations in the high-altitude Tibetan wolf that were selectively introgressed into the Tibetan mastiff, a high-altitude dog breed that is renowned for its hypoxia tolerance. Experiments revealed that the introgressed coding variants confer an increased Hb-O2 affinity in conjunction with an enhanced Bohr effect. We also document that affinity-enhancing mutations in the ß-globin gene of Tibetan wolf were originally derived via interparalog gene conversion from a tandemly linked ß-globin pseudogene. Thus, affinity-enhancing mutations were introduced into the ß-globin gene of Tibetan wolf via one form of intragenomic lateral transfer (ectopic gene conversion) and were subsequently introduced into the Tibetan mastiff genome via a second form of lateral transfer (introgression). Site-directed mutagenesis experiments revealed that the increased Hb-O2 affinity requires a specific two-site combination of amino acid replacements, suggesting that the molecular underpinnings of Hb adaptation in Tibetan mastiff (involving mutations that arose in a nonexpressed gene and which originally fixed in Tibetan wolf) may be qualitatively distinct from functionally similar changes in protein function that could have evolved via sequential fixation of de novo mutations during the breed's relatively short duration of residency at high altitude.


Assuntos
Aclimatação/genética , Altitude , Canidae/genética , Hemoglobinas/fisiologia , Substituição de Aminoácidos , Animais , Conversão Gênica , Modelos Moleculares , Mutação
8.
Biochem Soc Trans ; 47(3): 933-944, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31189733

RESUMO

All analyzed haloarachea are polyploid. In addition, haloarchaea contain more than one type of chromosome, and thus the gene dosage can be regulated independently on different replicons. Haloarchaea and several additional archaea have more than one replication origin on their major chromosome, in stark contrast with bacteria, which have a single replication origin. Two of these replication origins of Haloferax volcanii have been studied in detail and turned out to have very different properties. The chromosome copy number appears to be regulated in response to growth phases and environmental factors. Archaea typically contain about two Origin Recognition Complex (ORC) proteins, which are homologous to eukaryotic ORC proteins. However, haloarchaea are the only archaeal group that contains a multitude of ORC proteins. All 16 ORC protein paralogs from H. volcanii are involved in chromosome copy number regulation. Polyploidy has many evolutionary advantages for haloarchaea, e.g. a high resistance to desiccation, survival over geological times, and the relaxation of cell cycle-specific replication control. A further advantage is the ability to grow in the absence of external phosphate while using the many genome copies as internal phosphate storage polymers. Very efficient gene conversion operates in haloarchaea and results in the unification of genome copies. Taken together, haloarchaea are excellent models to study many aspects of genome biology in prokaryotes, exhibiting properties that have not been found in bacteria.


Assuntos
Archaea/genética , Evolução Molecular , Conversão Gênica , Genes Arqueais , Poliploidia , Cromossomos de Archaea , Origem de Replicação
9.
Mol Cell ; 75(2): 252-266.e8, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31202577

RESUMO

Topoisomerase II (TOP2) relieves torsional stress by forming transient cleavage complex intermediates (TOP2ccs) that contain TOP2-linked DNA breaks (DSBs). While TOP2ccs are normally reversible, they can be "trapped" by chemotherapeutic drugs such as etoposide and subsequently converted into irreversible TOP2-linked DSBs. Here, we have quantified etoposide-induced trapping of TOP2ccs, their conversion into irreversible TOP2-linked DSBs, and their processing during DNA repair genome-wide, as a function of time. We find that while TOP2 chromatin localization and trapping is independent of transcription, it requires pre-existing binding of cohesin to DNA. In contrast, the conversion of trapped TOP2ccs to irreversible DSBs during DNA repair is accelerated 2-fold at transcribed loci relative to non-transcribed loci. This conversion is dependent on proteasomal degradation and TDP2 phosphodiesterase activity. Quantitative modeling shows that only two features of pre-existing chromatin structure-namely, cohesin binding and transcriptional activity-can be used to predict the kinetics of TOP2-induced DSBs.


Assuntos
Quebras de DNA de Cadeia Dupla , DNA Topoisomerases Tipo II/química , DNA/genética , Complexos Multiproteicos/química , Proteínas de Ligação a Poli-ADP-Ribose/química , Quebra Cromossômica , Cromossomos/genética , DNA/química , Reparo do DNA/genética , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Etoposídeo/química , Conversão Gênica/genética , Células HCT116 , Humanos , Cinética , Complexos Multiproteicos/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia , Torção Mecânica , Transcrição Genética , Translocação Genética/genética
10.
Nat Med ; 25(6): 890-897, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31160821

RESUMO

Monogenic disorders occur at a high frequency in human populations and are commonly inherited through the germline. Unfortunately, once the mutation has been transmitted to a child, only limited treatment options are available in most cases. However, means of correcting disease-causing nuclear and mitochondrial DNA mutations in gametes or preimplantation embryos have now been developed and are commonly referred to as germline gene therapy (GGT). We will discuss these novel strategies and provide a path forward for safe, high-efficiency GGT that may provide a promising new paradigm for preventing the passage of deleterious genes from parent to child.


Assuntos
Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/terapia , Terapia Genética/métodos , Mutação em Linhagem Germinativa , Criança , Reparo do DNA , DNA Mitocondrial/genética , Feminino , Fertilização In Vitro , Conversão Gênica , Terapia Genética/ética , Terapia Genética/legislação & jurisprudência , Humanos , Masculino , Terapia de Substituição Mitocondrial , Gravidez , Diagnóstico Pré-Implantação , Segurança
11.
Genetics ; 212(4): 1101-1119, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152071

RESUMO

Meiotic recombination shuffles genetic variation and promotes correct segregation of chromosomes. Rates of recombination vary on several scales, both within genomes and between individuals, and this variation is affected by both genetic and environmental factors. Social insects have extremely high rates of recombination, although the evolutionary causes of this are not known. Here, we estimate rates of crossovers and gene conversions in 22 colonies of the honeybee, Apis mellifera, and 9 colonies of the bumblebee, Bombus terrestris, using direct sequencing of 299 haploid drone offspring. We confirm that both species have extremely elevated crossover rates, with higher rates measured in the highly eusocial honeybee than the primitively social bumblebee. There are also significant differences in recombination rate between subspecies of honeybee. There is substantial variation in genome-wide recombination rate between individuals of both A. mellifera and B. terrestris and the distribution of these rates overlap between species. A large proportion of interindividual variation in recombination rate is heritable, which indicates the presence of variation in trans-acting factors that influence recombination genome-wide. We infer that levels of crossover interference are significantly lower in honeybees compared to bumblebees, which may be one mechanism that contributes to higher recombination rates in honeybees. We also find a significant increase in recombination rate with distance from the centromere, mirrored by methylation differences. We detect a strong transmission bias due to GC-biased gene conversion associated with noncrossover gene conversions. Our results shed light on the mechanistic causes of extreme rates of recombination in social insects and the genetic architecture of recombination rate variation.


Assuntos
Abelhas/genética , Troca Genética , Conversão Gênica , Variação Genética , Animais , Evolução Molecular , Comportamento Social
12.
Genetics ; 212(4): 1321-1336, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31147380

RESUMO

As multi-individual population-scale data become available, more complex modeling strategies are needed to quantify genome-wide patterns of nucleotide usage and associated mechanisms of evolution. Recently, the multivariate neutral Moran model was proposed. However, it was shown insufficient to explain the distribution of alleles in great apes. Here, we propose a new model that includes allelic selection. Our theoretical results constitute the basis of a new Bayesian framework to estimate mutation rates and selection coefficients from population data. We apply the new framework to a great ape dataset, where we found patterns of allelic selection that match those of genome-wide GC-biased gene conversion (gBGC). In particular, we show that great apes have patterns of allelic selection that vary in intensity-a feature that we correlated with great apes' distinct demographies. We also demonstrate that the AT/GC toggling effect decreases the probability of a substitution, promoting more polymorphisms in the base composition of great ape genomes. We further assess the impact of GC-bias in molecular analysis, and find that mutation rates and genetic distances are estimated under bias when gBGC is not properly accounted for. Our results contribute to the discussion on the tempo and mode of gBGC evolution, while stressing the need for gBGC-aware models in population genetics and phylogenetics.


Assuntos
Conversão Gênica , Hominidae/genética , Modelos Genéticos , Animais , Sequência Rica em GC , Genoma , Polimorfismo Genético
13.
Genome Biol Evol ; 11(7): 1723-1729, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31209488

RESUMO

Nature has found many ways to utilize transposable elements (TEs) throughout evolution. Many molecular and cellular processes depend on DNA-binding proteins recognizing hundreds or thousands of similar DNA motifs dispersed throughout the genome that are often provided by TEs. It has been suggested that TEs play an important role in the evolution of such systems, in particular, the rewiring of gene regulatory networks. One mechanism that can further enhance the rewiring of regulatory networks is nonallelic gene conversion between copies of TEs. Here, we will first review evidence for nonallelic gene conversion in TEs. Then, we will illustrate the benefits nonallelic gene conversion provides in rewiring regulatory networks. For instance, nonallelic gene conversion between TE copies offers an alternative mechanism to spread beneficial mutations that improve the network, it allows multiple mutations to be combined and transferred together, and it allows natural selection to work efficiently in spreading beneficial mutations and removing disadvantageous mutations. Future studies examining the role of nonallelic gene conversion in the evolution of TEs should help us to better understand how TEs have contributed to evolution.


Assuntos
Elementos de DNA Transponíveis/genética , Conversão Gênica/genética , Conversão Gênica/fisiologia , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/fisiologia , Humanos , Mutação/genética
14.
ISME J ; 13(9): 2173-2182, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31053830

RESUMO

Sequenced archaeal genomes are mostly smaller and more streamlined than typical bacterial genomes; however, members of the Methanosarcina genus within the Euryarchaeaota are a significant exception, with M. acetivorans being the largest archaeal genome (5.8 Mbp) sequenced thus far. This finding is partially explained by extensive gene duplication within Methanosarcina spp. Significantly, the evolutionary pressures leading to gene duplication and subsequent genome expansion have not been well investigated, especially with respect to biological methane production (methanogenesis), which is the key biological trait of these environmentally important organisms. In this study, we address this question by specifically probing the functional evolution of two methylamine-specific methyltransferase paralogs in members of the Methanosarcina genus. Using the genetically tractable strain, M. acetivorans, we first show that the two paralogs have distinct cellular functions: one being required for methanogenesis from methylamine, the other for use of methylamine as a nitrogen source. Subsequently, through comparative sequence analyses, we show that functional divergence of paralogs is primarily mediated by divergent evolution of the 5' regulatory region, despite frequent gene conversion within the coding sequence. This unique evolutionary paradigm for functional divergence of genes post-duplication underscores a divergent role for an enzyme singularly associated with methanogenic metabolism in other aspects of cell physiology.


Assuntos
Proteínas Arqueais/metabolismo , Conversão Gênica , Methanosarcina/enzimologia , Methanosarcina/genética , Metilaminas/metabolismo , Metiltransferases/metabolismo , Proteínas Arqueais/genética , Genoma Arqueal , Methanosarcina/metabolismo , Metiltransferases/genética
15.
PLoS Genet ; 15(4): e1007786, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30946740

RESUMO

At the molecular level, the evolution of new traits can be broadly divided between changes in gene expression and changes in protein-coding sequence. For proteins, the evolution of novel functions is generally thought to proceed through sequential point mutations or recombination of whole functional units. In Saccharomyces, the uptake of the sugar maltotriose into the cell is the primary limiting factor in its utilization, but maltotriose transporters are relatively rare, except in brewing strains. No known wild strains of Saccharomyces eubayanus, the cold-tolerant parent of hybrid lager-brewing yeasts (Saccharomyces cerevisiae x S. eubayanus), are able to consume maltotriose, which limits their ability to fully ferment malt extract. In one strain of S. eubayanus, we found a gene closely related to a known maltotriose transporter and were able to confer maltotriose consumption by overexpressing this gene or by passaging the strain on maltose. Even so, most wild strains of S. eubayanus lack native maltotriose transporters. To determine how this rare trait could evolve in naive genetic backgrounds, we performed an adaptive evolution experiment for maltotriose consumption, which yielded a single strain of S. eubayanus able to grow on maltotriose. We mapped the causative locus to a gene encoding a novel chimeric transporter that was formed by an ectopic recombination event between two genes encoding transporters that are unable to import maltotriose. In contrast to classic models of the evolution of novel protein functions, the recombination breakpoints occurred within a single functional domain. Thus, the ability of the new protein to carry maltotriose was likely acquired through epistatic interactions between independently evolved substitutions. By acquiring multiple mutations at once, the transporter rapidly gained a novel function, while bypassing potentially deleterious intermediate steps. This study provides an illuminating example of how recombination between paralogs can establish novel interactions among substitutions to create adaptive functions.


Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces/genética , Saccharomyces/metabolismo , Trissacarídeos/metabolismo , Sequência de Aminoácidos , Cerveja/microbiologia , Proteínas de Transporte/química , Evolução Molecular Direcionada , Fermentação , Proteínas Fúngicas/química , Conversão Gênica , Genes Fúngicos , Hibridização Genética , Proteínas de Transporte de Monossacarídeos/química , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , Filogenia , Proteínas Recombinantes de Fusão/química , Saccharomyces/crescimento & desenvolvimento , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Simportadores/química , Simportadores/genética , Simportadores/metabolismo
16.
Mol Biol Evol ; 36(6): 1201-1214, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30991417

RESUMO

Natural selection works best when the two alleles in a diploid organism are transmitted to offspring at equal frequencies. Despite this, selfish loci known as meiotic drivers that bias their own transmission into gametes are found throughout eukaryotes. Drive is thought to be a powerful evolutionary force, but empirical evolutionary analyses of drive systems are limited by low numbers of identified meiotic drive genes. Here, we analyze the evolution of the wtf gene family of Schizosaccharomyces pombe that contains both killer meiotic drive genes and suppressors of drive. We completed assemblies of all wtf genes for two S. pombe isolates, as well as a subset of wtf genes from over 50 isolates. We find that wtf copy number can vary greatly between isolates and that amino acid substitutions, expansions and contractions of DNA sequence repeats, and nonallelic gene conversion between family members all contribute to dynamic wtf gene evolution. This work demonstrates the power of meiotic drive to foster rapid evolution and identifies a recombination mechanism through which transposons can indirectly mobilize meiotic drivers.


Assuntos
Evolução Molecular , Conversão Gênica , Schizosaccharomyces/genética , Genes Fúngicos , Padrões de Herança , Meiose , Anotação de Sequência Molecular , Família Multigênica , Sequências Repetitivas de Ácido Nucleico
17.
Genome Biol ; 20(1): 69, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30982471

RESUMO

BACKGROUND: Sequence exchange between homologous chromosomes through crossing over and gene conversion is highly conserved among eukaryotes, contributing to genome stability and genetic diversity. A lack of recombination limits breeding efforts in crops; therefore, increasing recombination rates can reduce linkage drag and generate new genetic combinations. RESULTS: We use computational analysis of 13 recombinant inbred mapping populations to assess crossover and gene conversion frequency in the hexaploid genome of wheat (Triticum aestivum). We observe that high-frequency crossover sites are shared between populations and that closely related parents lead to populations with more similar crossover patterns. We demonstrate that gene conversion is more prevalent and covers more of the genome in wheat than in other plants, making it a critical process in the generation of new haplotypes, particularly in centromeric regions where crossovers are rare. We identify quantitative trait loci for altered gene conversion and crossover frequency and confirm functionality for a novel RecQ helicase gene that belongs to an ancient clade that is missing in some plant lineages including Arabidopsis. CONCLUSIONS: This is the first gene to be demonstrated to be involved in gene conversion in wheat. Harnessing the RecQ helicase has the potential to break linkage drag utilizing widespread gene conversions.


Assuntos
Troca Genética , Conversão Gênica , Triticum/genética , Genoma de Planta , Poliploidia , Sequenciamento Completo do Genoma
18.
Life Sci Alliance ; 2(2)2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31023833

RESUMO

Meiotic recombination has strong, but poorly understood effects on short tandem repeat (STR) instability. Here, we screened thousands of single recombinant products with sperm typing to characterize the role of polymorphic poly-A repeats at a human recombination hotspot in terms of hotspot activity and STR evolution. We show that the length asymmetry between heterozygous poly-A's strongly influences the recombination outcome: a heterology of 10 A's (9A/19A) reduces the number of crossovers and elevates the frequency of non-crossovers, complex recombination products, and long conversion tracts. Moreover, the length of the heterology also influences the STR transmission during meiotic repair with a strong and significant insertion bias for the short heterology (6A/7A) and a deletion bias for the long heterology (9A/19A). In spite of this opposing insertion-/deletion-biased gene conversion, we find that poly-A's are enriched at human recombination hotspots that could have important consequences in hotspot activation.


Assuntos
Troca Genética/genética , Heterozigoto , Meiose/genética , Repetições de Microssatélites/genética , Poli A/genética , Alelos , Conversão Gênica/genética , Genótipo , Haplótipos/genética , Humanos , Masculino , Instabilidade de Microssatélites , Taxa de Mutação , Polimorfismo de Nucleotídeo Único/genética , Espermatozoides/citologia , Doadores de Tecidos
19.
Mol Biol Evol ; 36(6): 1134-1147, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30828717

RESUMO

As limits on O2 availability during submergence impose severe constraints on aerobic respiration, the oxygen binding globin proteins of marine mammals are expected to have evolved under strong evolutionary pressures during their land-to-sea transition. Here, we address this question for the order Sirenia by retrieving, annotating, and performing detailed selection analyses on the globin repertoire of the extinct Steller's sea cow (Hydrodamalis gigas), dugong (Dugong dugon), and Florida manatee (Trichechus manatus latirostris) in relation to their closest living terrestrial relatives (elephants and hyraxes). These analyses indicate most loci experienced elevated nucleotide substitution rates during their transition to a fully aquatic lifestyle. While most of these genes evolved under neutrality or strong purifying selection, the rate of nonsynonymous/synonymous replacements increased in two genes (Hbz-T1 and Hba-T1) that encode the α-type chains of hemoglobin (Hb) during each stage of life. Notably, the relaxed evolution of Hba-T1 is temporally coupled with the emergence of a chimeric pseudogene (Hba-T2/Hbq-ps) that contributed to the tandemly linked Hba-T1 of stem sirenians via interparalog gene conversion. Functional tests on recombinant Hb proteins from extant and ancestral sirenians further revealed that the molecular remodeling of Hba-T1 coincided with increased Hb-O2 affinity in early sirenians. Available evidence suggests that this trait evolved to maximize O2 extraction from finite lung stores and suppress tissue O2 offloading, thereby facilitating the low metabolic intensities of extant sirenians. In contrast, the derived reduction in Hb-O2 affinity in (sub)Arctic Steller's sea cows is consistent with fueling increased thermogenesis by these once colossal marine herbivores.


Assuntos
Adaptação Biológica , Evolução Molecular , Globinas/genética , Pseudogenes , Sirênios/genética , Animais , Conversão Gênica , Globinas/metabolismo , Masculino , Família Multigênica , Proteínas Mutantes Quiméricas , Oxigênio/metabolismo , Seleção Genética , Sirênios/metabolismo
20.
Genome Biol ; 20(1): 38, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30791939

RESUMO

BACKGROUND: The sharp increase of plant genome and transcriptome data provide valuable resources to investigate evolutionary consequences of gene duplication in a range of taxa, and unravel common principles underlying duplicate gene retention. RESULTS: We survey 141 sequenced plant genomes to elucidate consequences of gene and genome duplication, processes central to the evolution of biodiversity. We develop a pipeline named DupGen_finder to identify different modes of gene duplication in plants. Genes derived from whole-genome, tandem, proximal, transposed, or dispersed duplication differ in abundance, selection pressure, expression divergence, and gene conversion rate among genomes. The number of WGD-derived duplicate genes decreases exponentially with increasing age of duplication events-transposed duplication- and dispersed duplication-derived genes declined in parallel. In contrast, the frequency of tandem and proximal duplications showed no significant decrease over time, providing a continuous supply of variants available for adaptation to continuously changing environments. Moreover, tandem and proximal duplicates experienced stronger selective pressure than genes formed by other modes and evolved toward biased functional roles involved in plant self-defense. The rate of gene conversion among WGD-derived gene pairs declined over time, peaking shortly after polyploidization. To provide a platform for accessing duplicated gene pairs in different plants, we constructed the Plant Duplicate Gene Database. CONCLUSIONS: We identify a comprehensive landscape of different modes of gene duplication across the plant kingdom by comparing 141 genomes, which provides a solid foundation for further investigation of the dynamic evolution of duplicate genes.


Assuntos
Evolução Biológica , Duplicação Gênica , Genoma de Planta , Plantas/genética , Poliploidia , Bases de Dados como Assunto , Conversão Gênica , Expressão Gênica , Família Multigênica , Seleção Genética , Software
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