Going beyond SNPs: The role of structural genomic variants in adaptive evolution and species diversification

Citations Over TimeTop 1% of 2019 papers

Abstract

Although single-nucleotide polymorphism (SNPs) were initially thought to make-up the majority of selectable variation (Morin, Luikart, & Wayne, 2004; Sachidanandam et al., 2001), it is becoming increasingly recognized that structural variation represents a significant, yet often poorly understood, source of genetic variation. It is only within the past 10 years, aided by the development of genomic technologies such as high throughput and later third generation sequencing, that the extent of intra- and interspecific structural variation has been investigated in a number of nonmodel species (Chain & Feulner, 2014; Fan & Meyer, 2014). The term structural variation is used to define a region of DNA that shows a change in copy number (deletions, insertions and duplications), orientation (inversions), or chromosomal location (translocations, fusions) between individuals. Structural variation may occur both in coding and noncoding gene region of the genome, including in highly repetitive elements, such as transposons. In other words, structural variants can be balanced and show no specific loss or gain of DNA information, such as inversions of a genetic fragment or translocations of a stretch of DNA within or between chromosomes, or they can be unbalanced, where a part of the genome is lost (insertions/deletions) or duplicated (duplications), which is termed copy number variation (CNV). This Special Issue in Molecular Ecology provides a platform to showcase and highlight the very recent progress in understanding the role of genomic structural variants in adaptive evolution and species diversification. The contributions are varied, covering both animals and plants, and range from comparison of different kind of structural variants in the genome to bioinformatic approaches that can be used to characterize structural variants, experimental approaches that test the role of structural variants in adaptation and diversification to population-level studies that document the ecological determinants of structural variants and their adaptive significance in nature. The history of structural variants goes back to the beginning of this century, many years before scientists even had an understanding of what DNA was. It all started with the discovery of inversions, DNA regions that are flipped in orientation, which leads to the suppression of recombination in inversion heterozygotes (Butlin, 2005; Dobzhansky & Sturtevant, 1938). The discovery of inverted chromosomal regions was made when Alfred Sturtevant compared the chromosome maps of Drosophila melanogaster with those of D. simulans, a closely related species that he had described earlier (Sturtevant, 1913). He found that the interspecies chromosome maps were similar, except for a genomic region on the third chromosome, where one large part of the sequence was inverted (Sturtevant, 1921). In the years to follow, Sturtevant was able to obtain a sufficient numbers of mutants with the various inversion-containing chromosomes of D. melanogaster to establish that the dominant crossover suppressors were indeed inversions (Sturtevant & Mather, 1938). Afterwards, additional structural variants were discovered in a variety of species, with the notable discovery of transposable elements in maize (e.g., McClintock, 1931, McClintock, 1950). McClintock's work was revolutionary in that it suggested that an organism's genome is not a stationary entity, but rather is subject to alteration and rearrangement and changed the way scientists think about genetic patterns of inheritance. At the time the concept was met with criticism from the scientific community; however, the role of transposons eventually became widely appreciated and the community started to accept that genomic replication does not always follow a consistent pattern. McClintock was awarded the Nobel Prize in 1983 in recognition of this and her many other contributions to the field of genetics (Ravindran, 2012). Yet, starting in the 1970s, this rich literature largely sank from view with the rise of molecular genetics and the development of other markers, including microsatellites, amplified fragment length polymorphism (AFLPs) and more recently SNPs. In particular, the latest techniques provide cheap, high throughput methods for genotyping many SNP markers (e.g., Elshire et al., 2011), leading to studies of genetic variation being largely dominated by SNP variation. However, structural variants are present at significant frequencies in many populations and may contribute to important processes. For example, evidence is accumulating that gene dosage can be heavily affected by CNV with a profound effect on the functionality and the resulting evolutionary trajectories (Ha, Kim, & Chen, 2009). Yet, CNVs go mostly undetected by standard SNP genotyping methods. Likewise, young inversions may go undetected in sequencing analyses, because merely the linear order of DNA bases is changed initially and only the breakpoints carry SNP variants; however, the consequences on recombination in a species can be pronounced and have long-term effects on the fitness of specific inversion genotypes (Wellenreuther & Bernatchez, 2018). The study of the structural variation of the genome has recently gained momentum as we are currently witnessing major advances in the field of computational genomics with increasingly high quality whole-genome data and assemblies becoming available for nonmodel species. Furthermore, advances in long-read sequencing, optical mapping and novel assembly algorithms now provide incredible resolution to study the presence and absence of a variety of structural variants (Chakraborty et al., 2018; Lee et al., 2016). This is accompanied by simultaneous fast improvements in computational and statistical tools that together allow the extraction of reliable information of the location and effect of structural variants on the phenotype (e.g., Boetzer & Pirovano, 2014; Koren & Phillippy, 2015; Koren et al., 2017). Using these genomic and bioinformatics advances we can now dissect the nucleotide variation contained within these structural variants as well as their ecological and evolutionary significance with unprecedented detail. As a consequence of these discoveries, a growing number of geneticists and evolutionary biologists have recently shifted their attention from SNP markers towards bigger and more complex alterations in the genomic architecture thus going back to some of the oldest genetic markers. For example, we have recently witnessed a dramatic increase in the number of studies reporting the involvement of complex structural variants in several genomic disorders (Sanchis-Juan et al., 2018; Xia et al., 2017). The 24 articles in this Special Issue of Molecular Ecology, which embody a diverse collection of approaches and study systems, offer valuable lessons about the role of structural genomic variation in adaptation and species diversification. The contribution by Catanach, Deng, Charles, Bernatchez, and Wellenreuther (2019) highlights the frequent nature of structural variants and their nonrandom distribution in the genome, thus underscoring the emergent tenet that structural variants offer important sources of genetic fuel for evolutionary processes. Specifically, they use replicate genome assemblies of the Australasian snapper Chrysophrys auratus to quantify the locations and prevalence of SNPs and structural variants of varied sizes, and showed that while SNPs were most common, that the number of base pairs affected by structural variants was almost three times higher compared to SNPs. The high number of structural variants indicates that some may have an impact on the phenotype and this was further supported by the finding that a sizeable portion of the structural variants were located in regions under putative selection, and that a third intersected in some way with genes. The prevalence of genome-wide structural variants was also investigated by Lucek, Gompert, and Nosil (2019) using a mate-pair sequencing and a population genomics framework in the stick insect Timema cristinae. The authors were able to describe numerous inversions, deletions, duplications throughout the genome. Although not detected by the mate-pair approach, the study also considers one large structural variant that has formerly been described, which shows reduced recombination and harbours genes controlling colour-pattern and therewith leads to an accentuated differentiation between ecotypes. This study is a prime example of the need to go beyond the mere measure of SNPs when studying evolutionary processes and that knowledge of structural variants can be relevant to understand variation at the intraspecific level or during early divergence. They also highlight that while not all structural variants would be expected a priori to be involved in ecotype differentiation, that some variant characteristics, such as large size and being able to protect regions from gene flow (e.g., inversions) would increase the likelihood of them being involved in adaptive processes compared to others. Many inversions fulfil these criteria and this is partly the reason why inversions have seen a surge in popularity over the last decade due to their clear association with adaptive phenotypes, behaviour, mating strategies and speciation (Wellenreuther & Bernatchez, 2018). The first contribution on inversions by Cheng and Kirkpatrick (2019) investigates the intriguing observation in varied taxa that inversions fix at a faster rate on the X chromosome compared to autosomes. Using the Drosophila system they show that X-linked inversions are often larger than their autosomal counterparts and capture a staggering 67% more genes than autosomal inversions. They combine this empirical result with a population genetic model showing that the same conditions that favour higher fixation rates of inversion on the X chromosome also favour larger inversions. Together these results indicate that inversions on the X chromosome may strongly influence the evolution of sex chromosomes. Hooper, Griffith, and Price (2019) also explore inversions on sex chromosomes by studying two subspecies of long-tailed finches and integrating population genomics with phenotype data associated with fitness differences, such as bill colour. With this, they are able to detail Z-linked inversion related differentiation between the two subspecies; however, they also find that the frequency cline does not coincide with the autosome nor bill colour; a major phenotypic difference between the subspecies. They integrate these findings to argue that inversions on the sex chromosome could serve as good candidates for structural variants that are tightly linked to reproductive isolation. In their contribution to this special issue, Kapun and Flatt (2019) revisit the species where inversions where first described, the vinegar fruitfly Drosophila melanogaster. Since the original discovery, significant advances in the field have come from the same system and they provide an indepth and thorough review of the rich work until today. In particular, they also include a meta-analysis of the geographic distribution of four major cosmopolitan inversions, and worldwide patterns of clinality. The evidence that they put together suggests that large cosmopolitan inversions in this species have an adaptive significance and are under balancing selection. Fuller, Koury, Phadnis, and Schaeffer (2019) provide a complementary review on the history of inversion research in D. pseudoobscura and D. persimilis, notably going also over the details by which recombination is suppressed in inversion heterozygotes. By summarizing the large body of work on the inversions both at the intraspecific and interspecific level, the review concludes that inversions often underlie adaptation to heterogeneous environments, are governed by balancing selection, and how this can transition to fixed differences between species. Korunes and Noor (2019) work on the same species pair to measure noncrossover gene conversion rates in intra- and interspecific crosses. They detect that the gene conversion rate can be high within inversions, and this holds true, even near breakpoints. However, conversion rate is considerably lower in regions of high divergence, yet the rate is still higher than in similar regions of collinear genome. Korunes and Noor (2019) claim that these findings force us to rethink the extent that recombination is reduced in inversions and how this may affect the build-up of divergence. Specifically, they argue for a more nuanced view as some exchange is still occurring, even at the interspecific level. That being said, the extent of homogenisation remains limited because the length of the fragments homogenized by gene conversion is still very short compared to the size of the overall rearrangement, or compared to the extent of genetic exchange due to true crossovers. Puig Giribets et al. (2019) examine the role of inversions in the evolutionary responses to heat shock variation in Drosophila subobscura to understand why flies homokaryotypic for the warm-climate chromosomal arrangement exhibit basal Hsp70 protein levels after a heat shock treatment similar to those attained by their cold-climate counterpart. They detected a mostly common pattern of cytological location, number of cis-regulatory elements and gene copies among these inversions and found that they evolve in concert through gene conversion. The pattern of concerted evolution, however, is strongly structured and idiosyncratic across lineages as expected from the barriers to interchromosomal genetic exchange. This finding points to a previously unrealized link between inversions and concerted evolution, with potentially major implications for understanding genome evolution. Newly inversions could patterns of concerted evolution the orientation and between which may on their location, and inversions could be for they specific adaptive patterns of concerted evolution through their interchromosomal recombination suppression with many inversion is that the genes under the inversion are to because the regions shows study by et al. (2019) to this issue, and a to dissect the genes an inversion of the They this by for within and on the individuals. By they are able to characterize the putative of adaptation to and provide a for an original to characterize the link and the genetic of adaptation within a and (2019) the phenotypic effects of an inversion to between and of the In particular, they the that to adaptation the as by the recombination suppression & test this, they for history that between and a more collinear species. they found a chromosomal region at two adaptive that were associated with history in the absence of the With this, the contribution by and (2019) provides one of the where empirical for the recombination suppression could be found to when inversions system has been the of the inversion breakpoints. et al. (2019) study the inversion breakpoints with a of long-read and in the By inversions associated with high and populations they found that the were well that inversions are and associated with adaptation to and detected an additional rearrangement on the same The detected breakpoints were mostly of and transposable elements, in with a that is governed by et al. (2019) yet in inversion that is the discovery and reporting of structural variants because only the major inversions are which it to their prevalence and in evolutionary Using a on which the of recombination in and patterns of in the et al. detected no than in the of these showed variation in frequency between of a role in Although the does not allow to that these are indeed inversions, it represents an to detect structural variants at a It be however, that the association between inversions and is not always that to not in species by large population size and high gene such as the et al. (2019) test the that chromosomal inversions are an important for reproductive between in the of gene They found that frequencies of the inversions between the but they could not these differences to reproductive leading them to that thus other processes to reproductive in this This contribution highlights the need to use more approaches to study and that are one of many together to divergence. and (2019) provide example ecotype with an inversion polymorphism by studying the complex in the and of the this, they and and detected that the chromosomal inversion on many genes over and were present at different frequencies between in and those that had to a This indicates that the inversion is associated with the phenotype and but also that the link is not genomic regions are associated with and (2019) the large associated with in the where are by a or The of this species by inversions, but it is not yet clear inversions are a or consequence of the of results that between in the of mating gene flow from the to the As this study that variants may and of the mating system which influence the population in this species. are also in this Special and et al. (2019) investigates the chromosomal between chromosomes and which is in some are intriguing because they can to inversions and the rate of recombination in some crosses. They use populations in the of the to the genetic contribution of SNPs the chromosomal to the genetic between They overall population using SNPs and to a between the two However, when patterns of variation of the chromosomal they found high reduced in the and between the and the population on was times compared to the variation and the frequency of the was associated with This association strongly that this rearrangement may contribute adaptation This indicates that adaptive of major may be more important than processes for common structural variant is CNVs and their role in the of evolution from their effect on gene dosage and by gene The contribution by et al. (2019) the role of gene CNV in adaptation of the and provides empirical evidence that copy number variants of this are associated with that are under selection. work suggests that and a novel system for the molecular of gene et al. (2019) use genomic sequence data from the to a to detect CNV of coding regions in the closely related genome and to that variation to several They used from two from and and found CNV in of the genes and of the CNVs as significant to or They the significant variation to for to in the and to in the this work represents an important in genomic of intraspecific structural both by that CNV is more common than previously expected of coding and by and ecological for several of the variants that can to the generation of duplicated is by transposable elements that are present in all and that can from one location in the genome to sequencing methods have the to study population at the genome-wide most of the studies the of a limited number of et al. (2019) the genome-wide distribution of insertions in a young and species and using a genome from They used this data to test the contribution of in evolutionary The data that the copy numbers in the that they have within a transposons to be to repetitive regions of the genome that to it to or genome-wide can the in the et al. (2019) of the Drosophila population genomics sequencing data to document the of in a large of Drosophila melanogaster This them to show that while the is population no clear was for transposable or divergence. Yet, they several that were present at high frequencies and located in genomic regions with a high recombination which could be of selection. their results patterns of association between the frequency of insertions and some and variation between and further that at some of the they could a role in adaptation across and (2019) investigated the Drosophila cline in by populations of D. melanogaster and populations of D. from across The authors find a of in D. melanogaster to D. simulans, but no effect of on or frequencies in species. the absence of the authors argue that this does not a limited role for in adaptation and a complex between the presence of recombination rate and that for further The work by and (2019) on further the in which they can contribute to adaptation and by the molecular by which the genetic They also how the are affected by which be relevant in understanding how or species to and (2019) study the to test to what extent the of in regions their by and the presence of can the recombination this, they measure how and recombination at a chromosomes. The detected of to in length and found that a majority of these were in genes related to relevant such as responses to or This is consistent with evidence of at a through frequency or results are consistent with the that recombination and thus with in of linked adaptive in a study by et al. (2019) provides an important contribution to understand how genetic elements may and to reproductive isolation. They show that between and maps to a gene a protein and gene test that of at two evidence for a role of transposons in the generation of The that structural genomic variants provide genetic that provides a to fuel important evolutionary from mating to adaptation and is the way that dissect and the genomic of species. structural variants were previously to be they are now recognized as the source of genetic variation that can affect more bases than number and other genetic The contributions in this Special Issue highlight that the of structural variants in evolutionary genetics and molecular provide a more view of the role of genetic variants in adaptation and diversification. one an number of studies show that inversions are in species et al., that they may the of several et al., et al., et al., and can adaptive et al., & Puig Giribets et al., the other these studies also highlight that the link between structural variants and adaptation is not always studies in this special also show that while inversions have an overall in recombination gene conversion is still a force that be for & studying all structural variants or different and of structural variants such as deletions, duplications and inversions) the evidence for a link with adaptation can indeed be et al., et al., et al., et al., with some in adaptive regions and of variants in the genome. remains to be about their evolutionary role in it is becoming increasingly clear that structural variants are important to when studying genetic and genome evolution, and as they can no be improvements in structural variant and be a to the impact of these of variants on evolution, that increasingly with improvements and of long-read sequencing methods are at breakpoints at a it to the that to variant which is a to understand the processes that to the evolution and of structural evidence points towards a role of large inversions in but this is because of a or because they a larger number of potentially adaptive genes is still and some the to structural variants would allow for a population genetic framework that can use of frequency to the evolutionary similar to the framework used for SNPs. these can now be for structural variants, which allow us to gain knowledge of their ecological and evolutionary the first of the all authors the

Related Papers

• → Dynamics and adaptive benefits of modular protein evolution(2013)110 cited
• → Human evolution: When admixture met selection(2023)1 cited
• → Advances on molecular mechanism of the adaptive evolution of Chiroptera (bats).(2015)
• → SYNDACTYLUS PHYLOGENIES: THE ROLE OF GENE EXCHANGE IN ADAPTIVE EVOLUTION(2008)
• → Megaevolutionary dynamics in reptiles and the role of adaptive radiations in evolutionary innovation(2020)