scholarly journals Background selection as baseline for nucleotide variation across the Drosophila genome

2014 ◽  
Author(s):  
Josep M Comeron
Keyword(s):  
Balancing Selection ◽  
Genetic Maps ◽  
Drosophila Genome ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Entire Genome ◽  
Genome Wide ◽  
Intergenic Regions ◽  
Selection Parameters ◽  
Genomic Regions

The constant removal of deleterious mutations by natural selection causes a reduction in neutral diversity and efficacy of selection at genetically linked sites (a process called Background Selection, BGS). Population genetic studies, however, often ignore BGS effects when investigating demographic events or the presence of other types of selection. To obtain a more realistic evolutionary expectation that incorporates the unavoidable consequences of deleterious mutations, we generated high-resolution landscapes of variation across the Drosophila melanogaster genome under a BGS scenario independent of polymorphism data. We find that BGS plays a significant role in shaping levels of variation across the entire genome, including long introns and intergenic regions distant from annotated genes. We also find that a very large percentage of the observed variation in diversity across autosomes can be explained by BGS alone, up to 70% across individual chromosome arms, thus indicating that BGS predictions can be used as baseline to infer additional types of selection and demographic events. This approach allows detecting several outlier regions with signal of recent adaptive events and selective sweeps. The use of a BGS baseline, however, is particularly appropriate to investigate the presence of balancing selection and our study exposes numerous genomic regions with the predicted signature of higher polymorphism than expected when a BGS context is taken into account. Importantly, we show that these conclusions are robust to the mutation and selection parameters of the BGS model. Finally, analyses of protein evolution together with previous comparisons of genetic maps between Drosophila species, suggest temporally variable recombination landscapes and thus, local BGS effects that may differ between extant and past phases. Because genome-wide BGS and temporal changes in linkage effects can skew approaches to estimate demographic and selective events, future analyses should incorporate BGS predictions and capture local recombination variation across genomes and along lineages.

scholarly journals Transition from background selection to associative overdominance promotes diversity in regions of low recombination

2019 ◽  
Author(s):  
Kimberly J. Gilbert ◽  
Fanny Pouyet ◽  
Laurent Excoffier ◽  
Stephan Peischl
Keyword(s):  
Genetic Diversity ◽  
Balancing Selection ◽  
Purifying Selection ◽  
Heterozygote Advantage ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Recombination Rates ◽  
Locus Model ◽  
Genome Wide ◽  
Linked Selection

SummaryLinked selection is a major driver of genetic diversity. Selection against deleterious mutations removes linked neutral diversity (background selection, BGS, Charlesworth et al. 1993), creating a positive correlation between recombination rates and genetic diversity. Purifying selection against recessive variants, however, can also lead to associative overdominance (AOD, Ohta 1971, Zhao & Charlesworth, 2016), due to an apparent heterozygote advantage at linked neutral loci that opposes the loss of neutral diversity by BGS. Zhao & Charlesworth (2016) identified the conditions when AOD should dominate over BGS in a single-locus model and suggested that the effect of AOD could become stronger if multiple linked deleterious variants co-segregate. We present a model describing how and under which conditions multi-locus dynamics can amplify the effects of AOD. We derive the conditions for a transition from BGS to AOD due to pseudo-overdominance (Ohta & Kimura 1970), i.e. a form of balancing selection that maintains complementary deleterious haplotypes that mask the effect of recessive deleterious mutations. Simulations confirm these findings and show that multi-locus AOD can increase diversity in low recombination regions much more strongly than previously appreciated. While BGS is known to drive genome-wide diversity in humans (Pouyet et al. 2018), the observation of a resurgence of genetic diversity in regions of very low recombination is indicative of AOD. We identify 21 such regions in the human genome showing clear signals of multi-locus AOD. Our results demonstrate that AOD may play an important role in the evolution of low recombination regions of many species.

scholarly journals Defining the functional significance of intergenic transcribed regions

2017 ◽  
Author(s):  
John P. Lloyd ◽  
Zing Tsung-Yeh Tsai ◽  
Rosalie P. Sowers ◽  
Nicholas L. Panchy ◽  
Shin-Han Shiu
Keyword(s):  
Flowering Plant ◽  
Sequence Structure ◽  
Transcriptional Noise ◽  
Novel Genes ◽  
Protein Coding ◽  
Genome Wide ◽  
Intergenic Regions ◽  
Flowering Plant Species ◽  
Genomic Regions ◽  
Rna Genes

ABSTRACTWith advances in transcript profiling, the presence of transcriptional activities in intergenic regions has been well established. However, whether intergenic expression reflects transcriptional noise or activity of novel genes remains unclear. We identified intergenic transcribed regions (ITRs) in 15 diverse flowering plant species and found that the amount of intergenic expression correlates with genome size, a pattern that could be expected if intergenic expression is largely nonfunctional. To further assess the functionality of ITRs, we first built machine learning classifiers using Arabidopsis thaliana as a model that accurately distinguish functional sequences (phenotype genes) and likely nonfunctional ones (pseudogenes and unexpressed intergenic regions) by integrating 93 biochemical, evolutionary, and sequence-structure features. Next, by applying the models genome-wide, we found that 4,427 ITRs (38%) and 796 annotated ncRNAs (44%) had features significantly similar to benchmark protein-coding or RNA genes and thus were likely parts of functional genes. Approximately 60% of ITRs and ncRNAs were more similar to nonfunctional sequences and were likely transcriptional noise. The predictive framework established here provides not only a comprehensive look at how functional, genic sequences are distinct from likely nonfunctional ones, but also a new way to differentiate novel genes from genomic regions with noisy transcriptional activities.

scholarly journals Widespread selection and gene flow shape the genomic landscape during a radiation of monkeyflowers

2018 ◽  
Author(s):  
Sean Stankowski ◽  
Madeline A. Chase ◽  
Allison M. Fuiten ◽  
Murillo F. Rodrigues ◽  
Peter L. Ralph ◽  
...  
Keyword(s):  
Gene Flow ◽  
Local Density ◽  
Background Selection ◽  
Deleterious Mutations ◽  
Evolutionary Processes ◽  
Genome Wide ◽  
Genomic Landscape ◽  
Genome Features ◽  
Genomic Studies ◽  
Genomic Basis

AbstractSpeciation genomic studies aim to interpret patterns of genome-wide variation in light of the processes that give rise to new species. However, interpreting the genomic ‘landscape’ of speciation is difficult, because many evolutionary processes can impact levels of variation. Facilitated by the first chromosome-level assembly for the group, we use whole-genome sequencing and simulations to shed light on the processes that have shaped the genomic landscape during a recent radiation of monkeyflowers. After inferring the phylogenetic relationships among the nine taxa in this radiation, we show that highly similar diversity (π) and differentiation (FST) landscapes have emerged across the group. Variation in these landscapes was strongly predicted by the local density of functional elements and the recombination rate, suggesting that the landscapes have been shaped by widespread natural selection. Using the varying divergence times between pairs of taxa, we show that the correlations between FST and genome features arose almost immediately after a population split and have become stronger over time. Simulations of genomic landscape evolution suggest that background selection (i.e., selection against deleterious mutations) alone is too subtle to generate the observed patterns, but scenarios that involve positive selection and genetic incompatibilities are plausible alternative explanations. Finally, tests for introgression among these taxa reveal widespread evidence of heterogeneous selection against gene flow during this radiation. Thus, combined with existing evidence for adaptation in this system, we conclude that the correlation in FST among these taxa informs us about the genomic basis of adaptation and speciation in this system.Author summaryWhat can patterns of genome-wide variation tell us about the speciation process? The answer to this question depends upon our ability to infer the evolutionary processes underlying these patterns. This, however, is difficult, because many processes can leave similar footprints, but some have nothing to do with speciation per se. For example, many studies have found highly heterogeneous levels of genetic differentiation when comparing the genomes of emerging species. These patterns are often referred to as differentiation ‘landscapes’ because they appear as a rugged topography of ‘peaks’ and ‘valleys’ as one scans across the genome. It has often been argued that selection against deleterious mutations, a process referred to as background selection, is primarily responsible for shaping differentiation landscapes early in speciation. If this hypothesis is correct, then it is unlikely that patterns of differentiation will reveal much about the genomic basis of speciation. However, using genome sequences from nine emerging species of monkeyflower coupled with simulations of genomic divergence, we show that it is unlikely that background selection is the primary architect of these landscapes. Rather, differentiation landscapes have probably been shaped by adaptation and gene flow, which are processes that are central to our understanding of speciation. Therefore, our work has important implications for our understanding of what patterns of differentiation can tell us about the genetic basis of adaptation and speciation.

scholarly journals Population Differentiation at the HLA Genes

2017 ◽  
Author(s):  
Débora Y. C. Brandt ◽  
Jônatas César ◽  
Jérôme Goudet ◽  
Diogo Meyer
Keyword(s):  
Population Differentiation ◽  
Balancing Selection ◽  
Global Scale ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Hla Genes ◽  
Genome Wide ◽  
Different Populations ◽  
Genomic Regions

ABSTRACTBalancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by FST. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle this issue, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. However, this result depends on accounting for the differences in allele frequency between selected and putatively neutral sites. Our finding of reduced differentiation at SNPs within HLA genes suggests a predominant role of shared selective pressures among populations at a global scale. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. This pattern was reproduced in simulations of overdominant selection. We conclude that population differentiation at the HLA genes is generally lower than genome-wide, but it may be higher for recently diverged population pairs, and that this pattern can be explained by a simple overdominance regime.

scholarly journals Elevated levels of expression associated with regions of the Drosophila genome that lack crossing over

2008 ◽  
Vol 4 (6) ◽  
pp. 758-761 ◽  
Author(s):  
Penelope R Haddrill ◽  
Fergal M Waldron ◽  
Brian Charlesworth
Keyword(s):  
Gene Expression ◽  
Drosophila Melanogaster ◽  
Molecular Evolution ◽  
Translational Efficiency ◽  
Crossing Over ◽  
Drosophila Genome ◽  
Deleterious Mutations ◽  
Fourth Chromosome ◽  
Genome Wide ◽  
Control Of Expression

The recombinational environment influences patterns of molecular evolution through the effects of Hill–Robertson interference. Here, we examine genome-wide patterns of gene expression with respect to recombinational environment in Drosophila melanogaster . We find that regions of the genome lacking crossing over exhibit elevated levels of expression, and this is most pronounced for genes on the entirely non-crossing over fourth chromosome. We find no evidence for differences in the patterns of gene expression between regions of high, intermediate and low crossover frequencies. These results suggest that, in the absence of crossing over, selection to maintain control of expression may be compromised, perhaps due to the accumulation of deleterious mutations in regulatory regions. Alternatively, higher gene expression may be evolving to compensate for defective protein products or reduced translational efficiency.

scholarly journals Mapping Quantitative Trait Loci onto Chromosome-Scale Pseudomolecules in Flax

2020 ◽  
Vol 3 (2) ◽  
pp. 28 ◽  
Author(s):  
Frank M. You ◽  
Sylvie Cloutier
Keyword(s):  
Quantitative Trait Loci ◽  
Candidate Genes ◽  
Quantitative Trait ◽  
Quantitative Traits ◽  
Snp Markers ◽  
Genetic Maps ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Trait Loci ◽  
Genomic Regions

Quantitative trait loci (QTL) are genomic regions associated with phenotype variation of quantitative traits. To date, a total of 313 QTL for 31 quantitative traits have been reported in 14 studies on flax. Of these, 200 QTL from 12 studies were identified based on genetic maps, the scaffold sequences, or the pre-released chromosome-scale pseudomolecules. Molecular markers for QTL identification differed across studies but the most used ones were simple sequence repeats (SSRs) or single nucleotide polymorphisms (SNPs). To uniquely map the SSR and SNP markers from different references onto the recently released chromosome-scale pseudomolecules, methods with several scripts and database files were developed to locate PCR- and SNP-based markers onto the same reference, co-locate QTL, and scan genome-wide candidate genes. Using these methods, 195 out of 200 QTL were successfully sorted onto the 15 flax chromosomes and grouped into 133 co-located QTL clusters; the candidate genes that co-located with these QTL clusters were also predicted. The methods and tools presented in this article facilitate marker re-mapping to a new reference, genome-wide QTL analysis, candidate gene scanning, and breeding applications in flax and other crops.

scholarly journals The Sheltered Genetic Load Linked to the S Locus in Plants: New Insights From Theoretical and Empirical Approaches in Sporophytic Self-Incompatibility

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 1105-1118 ◽  
Author(s):  
Violaine Llaurens ◽  
Lucy Gonthier ◽  
Sylvain Billiard
Keyword(s):  
Inbreeding Depression ◽  
Balancing Selection ◽  
Genetic Load ◽  
Relative Fitness ◽  
Self Incompatibility ◽  
Deleterious Mutations ◽  
Gas Treatment ◽  
Genomic Inbreeding ◽  
Genomic Regions ◽  
Empirical Approaches

Inbreeding depression and mating systems evolution are closely linked, because the purging of deleterious mutations and the fitness of individuals may depend on outcrossing vs. selfing rates. Further, the accumulation of deleterious mutations may vary among genomic regions, especially for genes closely linked to loci under balancing selection. Sporophytic self-incompatibility (SSI) is a common genetic mechanism in angiosperm that enables hermaphrodite plants to avoid selfing and promote outcrossing. The SSI phenotype is determined by the S locus and may depend on dominance relationships among alleles. Since most individuals are heterozygous at the S locus and recombination is suppressed in the S-locus region, it has been suggested that deleterious mutations could accumulate at genes linked to the S locus, generating a “sheltered load.” In this article, we first theoretically investigate the conditions generating sheltered load in SSI. We show that deleterious mutations can accumulate in linkage with specific S alleles, and particularly if those S alleles are dominant. Second, we looked for the presence of sheltered load in Arabidopsis halleri using CO2 gas treatment to overcome self-incompatibility. By examining the segregation of S alleles and measuring the relative fitness of progeny, we found significant sheltered load associated with the most dominant S allele (S15) of three S alleles tested. This sheltered load seems to be expressed at several stages of the life cycle and to have a larger effect than genomic inbreeding depression.

scholarly journals Highly structured homolog pairing reflects functional organization of the Drosophila genome

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jumana AlHaj Abed ◽  
Jelena Erceg ◽  
Anton Goloborodko ◽  
Son C. Nguyen ◽  
Ruth B. McCole ◽  
...  
Keyword(s):  
Functional Organization ◽  
Diploid Cell ◽  
Global Changes ◽  
Drosophila Genome ◽  
Detailed Structure ◽  
Active Chromatin ◽  
Homolog Pairing ◽  
Genome Wide ◽  
Diploid Cell Line ◽  
Genomic Regions

Abstract Trans-homolog interactions have been studied extensively in Drosophila, where homologs are paired in somatic cells and transvection is prevalent. Nevertheless, the detailed structure of pairing and its functional impact have not been thoroughly investigated. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, showing that homologs pair with varying precision genome-wide, in addition to establishing trans-homolog domains and compartments. We also elucidate the structure of pairing with unprecedented detail, observing significant variation across the genome and revealing at least two forms of pairing: tight pairing, spanning contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional implication genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing, including the disruption of some interaction peaks.

scholarly journals Recombination suppression and selection affect local ancestries in genomes of a migratory songbird

2021 ◽  
Author(s):  
Jun Ishigohoka ◽  
Karen Bascón-Cardozo ◽  
Andrea Bours ◽  
Janina Fuß ◽  
Arang Rhie ◽  
...  
Keyword(s):  
Zebra Finch ◽  
Genetic Relatedness ◽  
De Novo ◽  
Balancing Selection ◽  
Genomic Region ◽  
Genomic Islands ◽  
Background Selection ◽  
Recombination Suppression ◽  
Migratory Songbird ◽  
Genomic Regions

The patterns of genetic relatedness among individuals vary along the genome, representing fluctuation of local ancestry. The factors responsible for this variation have not been well studied in wild animals with ecological and behavioural relevance. Here, we characterise the genomic architecture of genetic relatedness in the Eurasian blackcap, an iconic songbird species in ecology and quantitative genetics of migratory behaviour. We identify 23 genomic regions with deviated local relatedness patterns, using a chromosome-level de novo assembly of the blackcap genome and whole-genome resequencing data of 179 individuals from nine populations with diverse migratory phenotypes. Five genomic regions show local relatedness patterns of polymorphic inversions, three of which are syntenic to polymorphic inversions known in the zebra finch. Phylogenetic analysis reveals these three polymorphic inversions evolved independently in the blackcap and zebra finch indicating convergence of polymorphic inversions. Population genetic analyses in these three inversions in the blackcap suggest balancing selection between two haplotypes in one locus and background selection in the other two loci. One genomic region with deviated local relatedness is under selection against gene flow by population-specific reduction in recombination rate. Other genomic islands including 11 pericentromeric regions consist of evolutionarily conserved and non-conserved recombination cold-spots under background selection. Two of these regions with non-conserved recombination suppression are known to be associated with population-specific migratory phenotypes, where local relatedness patterns support additional effects of population-specific selection. These results highlight how different forms of recombination suppression and selection jointly affect heterogeneous genomic landscape of local ancestries.

scholarly journals Time makes histone H3 modifications drift

2021 ◽  
Author(s):  
Roman Hillje ◽  
Lucilla Luzi ◽  
Stefano Amatori ◽  
Mirco Fanelli ◽  
Pier Giuseppe Pelicci ◽  
...  
Keyword(s):  
Caloric Restriction ◽  
Histone Modifications ◽  
Histone H3 ◽  
Transcription Start ◽  
Transcription Start Sites ◽  
Genome Wide ◽  
Restriction Diet ◽  
Intergenic Regions ◽  
Genomic Regions ◽  
Methylated Lysine

Abstract To disclose the epigenetic drift of time passing, we determined the genome-wide distributions of mono- and tri-methylated lysine 4 and acetylated and tri-methylated lysine 27 of histone H3 in the livers of healthy 3, 6 and 12 months old C57BL/6 mice. The comparison of different age profiles of histone H3 marks revealed global redistribution of histone H3 modifications with time, in particular in intergenic regions and near transcription start sites, as well as altered correlation between the profiles of different histone modifications. Moreover, feeding mice with caloric restriction diet, a treatment known to retard aging, preserved younger state of histone H3 in these genomic regions.

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