Population genomic evidence of selection on structural variants in a natural hybrid zone

Structural variants (SVs) can promote speciation by directly causing reproductive isolation or by suppressing recombination across large genomic regions. Whereas examples of each mechanism have been documented, systematic tests of the role of SVs in speciation are lacking. Here, we take advantage of long-read (Oxford nanopore) whole-genome sequencing and a hybrid zone between two Lycaeides butterfly taxa (L. melissa and Jackson Hole Lycaeides) to comprehensively evaluate genome-wide patterns of introgression for SVs and relate these patterns to hypotheses about speciation. We found >100,000 SVs segregating within or between the two hybridizing species. SVs and SNPs exhibited similar levels of genetic differentiation between species, with the exception of inversions, which were more differentiated. We detected credible variation in patterns of introgression among SV loci in the hybrid zone, with 562 of 1419 ancestry-informative SVs exhibiting genomic clines that deviating from null expectations based on genome-average ancestry. Overall, hybrids exhibited a directional shift towards Jackson Hole Lycaeides ancestry at SV loci, consistent with the hypothesis that these loci experienced more selection on average then SNP loci. Surprisingly, we found that deletions, rather than inversions, showed the highest skew towards excess introgression from Jackson Hole Lycaeides. Excess Jackson Hole Lycaeides ancestry in hybrids was also especially pronounced for Z-linked SVs and inversions containing many genes. In conclusion, our results show that SVs are ubiquitous and suggest that SVs in general, but especially deletions, might contribute disproportionately to hybrid fitness and thus (partial) reproductive isolation.

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Multi-locus interactions and the build-up of reproductive isolation

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2019.0543 ◽

2020 ◽

Vol 375 (1806) ◽

pp. 20190543 ◽

Cited By ~ 2

Author(s):

I. Satokangas ◽

S. H. Martin ◽

H. Helanterä ◽

J. Saramäki ◽

J. Kulmuni

Keyword(s):

Reproductive Isolation ◽

Empirical Work ◽

Hybrid Fitness ◽

Epistatic Interactions ◽

Genome Scans ◽

Theoretical Approaches ◽

Genome Wide ◽

Experimental Approaches ◽

Polymorphism Data

All genes interact with other genes, and their additive effects and epistatic interactions affect an organism's phenotype and fitness. Recent theoretical and empirical work has advanced our understanding of the role of multi-locus interactions in speciation. However, relating different models to one another and to empirical observations is challenging. This review focuses on multi-locus interactions that lead to reproductive isolation (RI) through reduced hybrid fitness. We first review theoretical approaches and show how recent work incorporating a mechanistic understanding of multi-locus interactions recapitulates earlier models, but also makes novel predictions concerning the build-up of RI. These include high variance in the build-up rate of RI among taxa, the emergence of strong incompatibilities producing localized barriers to introgression, and an effect of population size on the build-up of RI. We then review recent experimental approaches to detect multi-locus interactions underlying RI using genomic data. We argue that future studies would benefit from overlapping methods like ancestry disequilibrium scans, genome scans of differentiation and analyses of hybrid gene expression. Finally, we highlight a need for further overlap between theoretical and empirical work, and approaches that predict what kind of patterns multi-locus interactions resulting in incompatibilities will leave in genome-wide polymorphism data. This article is part of the theme issue ‘Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers’.

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Long read sequencing of 3,622 Icelanders provides insight into the role of structural variants in human diseases and other traits

10.1101/848366 ◽

2019 ◽

Cited By ~ 14

Author(s):

Doruk Beyter ◽

Helga Ingimundardottir ◽

Asmundur Oddsson ◽

Hannes P. Eggertsson ◽

Eythor Bjornsson ◽

...

Keyword(s):

Sequence Data ◽

P Value ◽

Repeat Region ◽

Structural Variants ◽

Genome Wide ◽

Population Average ◽

Long Reads ◽

Oxford Nanopore ◽

A Genome ◽

Long Read

Long-read sequencing (LRS) promises to improve characterization of structural variants (SVs), a major source of genetic diversity. We generated LRS data on 3,622 Icelanders using Oxford Nanopore Technologies, and identified a median of 22,636 SVs per individual (a median of 13,353 insertions and 9,474 deletions), spanning a median of 10 Mb per haploid genome. We discovered a set of 133,886 reliably genotyped SV alleles and imputed them into 166,281 individuals to explore their effects on diseases and other traits. We discovered an association with a rare (AF = 0.037%) deletion of the first exon of PCSK9. Carriers of this deletion have 0.93 mmol/L (1.31 SD) lower LDL cholesterol levels than the population average (p-value = 7.0·10−20). We also discovered an association with a multi-allelic SV inside a large repeat region, contained within single long reads, in an exon of ACAN. Within this repeat region we found 11 alleles that differ in the number of a 57 bp-motif repeat, and observed a linear relationship (0.016 SD per motif inserted, p = 6.2·10−18) between the number of repeats carried and height. These results show that SVs can be accurately characterized at population scale using long read sequence data in a genome-wide non-targeted approach and demonstrate how SVs impact phenotypes.

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Mapping and phasing of structural variation in patient genomes using nanopore sequencing

10.1101/129379 ◽

2017 ◽

Cited By ~ 4

Author(s):

Mircea Cretu Stancu ◽

Markus J. van Roosmalen ◽

Ivo Renkens ◽

Marleen Nieboer ◽

Sjors Middelkamp ◽

...

Keyword(s):

Single Molecule ◽

De Novo ◽

Structural Variants ◽

Human Genetic Disease ◽

Structural Genomic ◽

Short Read ◽

Sequencing Technologies ◽

Genome Wide ◽

Long Read ◽

Complex Structural

AbstractStructural genomic variants form a common type of genetic alteration underlying human genetic disease and phenotypic variation. Despite major improvements in genome sequencing technology and data analysis, the detection of structural variants still poses challenges, particularly when variants are of high complexity. Emerging long-read single-molecule sequencing technologies provide new opportunities for detection of structural variants. Here, we demonstrate sequencing of the genomes of two patients with congenital abnormalities using the ONT MinION at 11x and 16x mean coverage, respectively. We developed a bioinformatic pipeline - NanoSV - to efficiently map genomic structural variants (SVs) from the long-read data. We demonstrate that the nanopore data are superior to corresponding short-read data with regard to detection of de novo rearrangements originating from complex chromothripsis events in the patients. Additionally, genome-wide surveillance of SVs, revealed 3,253 (33%) novel variants that were missed in short-read data of the same sample, the majority of which are duplications < 200bp in size. Long sequencing reads enabled efficient phasing of genetic variations, allowing the construction of genome-wide maps of phased SVs and SNVs. We employed read-based phasing to show that all de novo chromothripsis breakpoints occurred on paternal chromosomes and we resolved the long-range structure of the chromothripsis. This work demonstrates the value of long-read sequencing for screening whole genomes of patients for complex structural variants.

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Limited intrinsic postzygotic reproductive isolation despite chromosomal rearrangements between closely related sympatric species of small ermine moths (Lepidoptera: Yponomeutidae)

Biological Journal of the Linnean Society ◽

10.1093/biolinnean/blz090 ◽

2019 ◽

Vol 128 (1) ◽

pp. 44-58 ◽

Cited By ~ 3

Author(s):

Katerina H Hora ◽

František Marec ◽

Peter Roessingh ◽

Steph B J Menken

Keyword(s):

Reproductive Isolation ◽

Parental Species ◽

Meiotic Chromosome ◽

Chromosomal Rearrangements ◽

Sympatric Species ◽

Hybrid Fitness ◽

New Host ◽

Closely Related Species ◽

Postzygotic Reproductive Isolation

Abstract In evolutionarily young species and sympatric host races of phytophagous insects, postzygotic incompatibility is often not yet fully developed, but reduced fitness of hybrids is thought to facilitate further divergence. However, empirical evidence supporting this hypothesis is limited. To assess the role of reduced hybrid fitness, we studied meiosis and fertility in hybrids of two closely related small ermine moths, Yponomeuta padella and Yponomeuta cagnagella, and determined the extent of intrinsic postzygotic reproductive isolation. We found extensive rearrangements between the karyotypes of the two species and irregularities in meiotic chromosome pairing in their hybrids. The fertility of reciprocal F1 and, surprisingly, also of backcrosses with both parental species was not significantly decreased compared with intraspecific offspring. The results indicate that intrinsic postzygotic reproductive isolation between these closely related species is limited. We conclude that the observed chromosomal rearrangements are probably not the result of an accumulation of postzygotic incompatibilities preventing hybridization. Alternative explanations, such as adaptation to new host plants, are discussed.

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Incomplete Reproductive Isolation in the Blue Mussel (Mytilus edulis and M. trossulus) Hybrid Zone in the Northwest Atlantic: Role of Gamete Interactions and Larval Viability

Biological Bulletin ◽

10.1086/bblv218n3p266 ◽

2010 ◽

Vol 218 (3) ◽

pp. 266-281 ◽

Cited By ~ 14

Author(s):

Marcelo B. B. Miranda ◽

David J. Innes ◽

Raymond J. Thompson

Keyword(s):

Reproductive Isolation ◽

Mytilus Edulis ◽

Hybrid Zone ◽

Blue Mussel ◽

Northwest Atlantic ◽

Gamete Interactions ◽

Incomplete Reproductive Isolation

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Phylogenomics provides new insight into evolutionary relationships and genealogical discordance in the reef-building coral genus Acropora

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2016.2182 ◽

2017 ◽

Vol 284 (1846) ◽

pp. 20162182 ◽

Cited By ~ 17

Author(s):

Natalie L. Rosser ◽

Luke Thomas ◽

Sean Stankowski ◽

Zoe T. Richards ◽

W. Jason Kennington ◽

...

Keyword(s):

Reproductive Isolation ◽

Future Research ◽

Nucleotide Polymorphisms ◽

Coral Genus ◽

Genome Wide ◽

A Genome ◽

Different Seasons ◽

Genetic Clusters ◽

Genome Level ◽

Genomic Regions

Understanding the genetic basis of reproductive isolation is a long-standing goal of speciation research. In recently diverged populations, genealogical discordance may reveal genes and genomic regions that contribute to the speciation process. Previous work has shown that conspecific colonies of Acropora that spawn in different seasons (spring and autumn) are associated with highly diverged lineages of the phylogenetic marker PaxC . Here, we used 10 034 single-nucleotide polymorphisms to generate a genome-wide phylogeny and compared it with gene genealogies from the PaxC intron and the mtDNA Control Region in 20 species of Acropora , including three species with spring- and autumn-spawning cohorts. The PaxC phylogeny separated conspecific autumn and spring spawners into different genetic clusters in all three species; however, this pattern was not supported in two of the three species at the genome level, suggesting a selective connection between PaxC and reproductive timing in Acropora corals. This genome-wide phylogeny provides an improved foundation for resolving phylogenetic relationships in Acropora and, combined with PaxC , provides a fascinating platform for future research into regions of the genome that influence reproductive isolation and speciation in corals.

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SvABA: Genome-wide detection of structural variants and indels by local assembly

10.1101/105080 ◽

2017 ◽

Cited By ~ 9

Author(s):

Jeremiah Wala ◽

Pratiti Bandopadhayay ◽

Noah Greenwald ◽

Ryan O’Rourke ◽

Ted Sharpe ◽

...

Keyword(s):

Variant Calling ◽

Accurate Method ◽

Structural Variants ◽

Sequencing Data ◽

Cancer Driver ◽

Insertion And Deletion ◽

Genome Wide ◽

Cancer Genomes ◽

Local Assembly ◽

Genomic Regions

AbstractStructural variants (SVs), including small insertion and deletion variants (indels), are challenging to detect through standard alignment-based variant calling methods. Sequence assembly offers a powerful approach to identifying SVs, but is difficult to apply at-scale genome-wide for SV detection due to its computational complexity and the difficulty of extracting SVs from assembly contigs. We describe SvABA, an efficient and accurate method for detecting SVs from short-read sequencing data using genome-wide local assembly with low memory and computing requirements. We evaluated SvABA’s performance on the NA12878 human genome and in simulated and real cancer genomes. SvABA demonstrates superior sensitivity and specificity across a large spectrum of SVs, and substantially improved detection performance for variants in the 20-300 bp range, compared with existing methods. SvABA also identifies complex somatic rearrangements with chains of short (< 1,000 bp) templated-sequence insertions copied from distant genomic regions. We applied SvABA to 344 cancer genomes from 11 cancer types, and found that templated-sequence insertions occur in ~4% of all somatic rearrangements. Finally, we demonstrate that SvABA can identify sites of viral integration and cancer driver alterations containing medium-sized SVs.

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Population Differentiation at the HLA Genes

10.1101/214668 ◽

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.

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Genome reorganization in F 1 hybrids uncovers the role of retrotransposons in reproductive isolation

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2014.2874 ◽

2015 ◽

Vol 282 (1804) ◽

pp. 20142874 ◽

Cited By ~ 31

Author(s):

Natacha Senerchia ◽

François Felber ◽

Christian Parisod

Keyword(s):

Reproductive Isolation ◽

Long Terminal Repeat Retrotransposons ◽

Plant Genome ◽

Species Boundaries ◽

Key To Species ◽

Differential Survival ◽

Genome Reorganization ◽

Genome Wide ◽

New Interactions

Interspecific hybridization leads to new interactions among divergent genomes, revealing the nature of genetic incompatibilities having accumulated during and after the origin of species. Conflicts associated with misregulation of transposable elements (TEs) in hybrids expectedly result in their activation and genome-wide changes that may be key to species boundaries. Repetitive genomes of wild wheats have diverged under differential dynamics of specific long terminal repeat retrotransposons (LTR-RTs), offering unparalleled opportunities to address the underpinnings of plant genome reorganization by selfish sequences. Using reciprocal F 1 hybrids between three Aegilops species, restructuring and epigenetic repatterning was assessed at random and LTR-RT sequences with amplified fragment length polymorphism and sequence-specific amplified polymorphisms as well as their methylation-sensitive counterparts, respectively. Asymmetrical reorganization of LTR-RT families predicted to cause conflicting interactions matched differential survival of F 1 hybrids. Consistent with the genome shock model, increasing divergence of merged LTR-RTs yielded higher levels of changes in corresponding genome fractions and lead to repeated reorganization of LTR-RT sequences in F 1 hybrids. Such non-random reorganization of hybrid genomes is coherent with the necessary repression of incompatible TE loci in support of hybrid viability and indicates that TE-driven genomic conflicts may represent an overlooked factor supporting reproductive isolation.

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