Transposable elements (TEs) are mobile genetic elements that parasitize genomes by semi-autonomously increasing their own copy number within the host genome. While TEs are important for genome evolution, appropriate methods for performing unbiased genome-wide surveys of TE variation in natural populations have been lacking. Here, we describe a novel and cost-effective approach for estimating population frequencies of TE insertions using paired-end Illumina reads from a pooled population sample. Importantly, the method treats insertions present in and absent from the reference genome identically, allowing unbiased TE population frequency estimates. We apply this method to data from a natural Drosophila melanogaster population from Portugal. Consistent with previous reports, we show that low recombining genomic regions harbor more TE insertions and maintain insertions at higher frequencies than do high recombining regions. We conservatively estimate that there are almost twice as many “novel” TE insertion sites as sites known from the reference sequence in our population sample (6,824 novel versus 3,639 reference sites, with on average a 31-fold coverage per insertion site). Different families of transposable elements show large differences in their insertion densities and population frequencies. Our analyses suggest that the history of TE activity significantly contributes to this pattern, with recently active families segregating at lower frequencies than those active in the more distant past. Finally, using our high-resolution TE abundance measurements, we identified 13 candidate positively selected TE insertions based on their high population frequencies and on low Tajima's D values in their neighborhoods.
Meiosis is a potentially important source of germline mutations, as sites of meiotic recombination experience recurrent double-strand breaks (DSBs). However, evidence for a local mutagenic effect of recombination from population sequence data has been equivocal, likely because mutation is only one of several forces shaping sequence variation. By sequencing large numbers of single crossover molecules obtained from human sperm for two recombination hotspots, we find direct evidence that recombination is mutagenic: Crossovers carry more de novo mutations than nonrecombinant DNA molecules analyzed for the same donors and hotspots. The observed mutations were primarily CG to TA transitions, with a higher frequency of transitions at CpG than non-CpGs sites. This enrichment of mutations at CpG sites at hotspots could predominate in methylated regions involving frequent single-stranded DNA processing as part of DSB repair. In addition, our data set provides evidence that GC alleles are preferentially transmitted during crossing over, opposing mutation, and shows that GC-biased gene conversion (gBGC) predominates over mutation in the sequence evolution of hotspots. These findings are consistent with the idea that gBGC could be an adaptation to counteract the mutational load of recombination. meiotic recombination | crossover | sequence evolution | biased gene conversion | mutation M eiotic recombination, localized in recombination hotspots, not only increases genetic diversity via the formation of new haplotypes but is also an important driver of sequence evolution. The binding sites used by the human recombination machinery involving PRDM9 (PR domain containing 9) are more eroded in humans than the same sequences in chimps, given that PRDM9 in chimps uses different binding sites (1). Moreover, regions in close vicinity to these PRDM9 binding sites also showed a significant enrichment of polymorphisms in humans (2). In addition, within-and between-species sequence diversity positively correlates with regions of high recombination activity in humans (3-7) and other eukaryotes (reviewed in refs. 8-10).One process recognized as a major evolutionary force reshaping the genomic nucleotide landscape at recombination hotspots, as shown in humans (6), chimpanzees (6, 11), mice (12), yeast (13), and metazoans (14), is GC-biased gene conversion (gBGC). In gBGC, the repair of heteroduplex tracts formed during meiotic recombination leads to the nonMendelian segregation of alleles favoring GC over AT variants. The precise molecular mechanisms leading to gBGC have yet to be unraveled, but experimental evidence has shown that in crossovers (COs) of fission yeast, GC alleles can be overtransmitted within ∼1-2 kb in length of the double-strand break (DSB) region (13), implicating mismatch repair (15).However, it is also plausible that the higher sequence variation observed at recombination hotspots is a result of a mutagenic effect of recombination: meiotic recombination is initiated by DSBs, which are associated with an increased mutati...
Various approaches can be applied to uncover the genetic basis of natural phenotypic variation, each with their specific strengths and limitations. Here, we use a replicated genome-wide association approach (Pool-GWAS) to fine-scale map genomic regions contributing to natural variation in female abdominal pigmentation in Drosophila melanogaster, a trait that is highly variable in natural populations and highly heritable in the laboratory. We examined abdominal pigmentation phenotypes in approximately 8000 female European D. melanogaster, isolating 1000 individuals with extreme phenotypes. We then used whole-genome Illumina sequencing to identify single nucleotide polymorphisms (SNPs) segregating in our sample, and tested these for associations with pigmentation by contrasting allele frequencies between replicate pools of light and dark individuals. We identify two small regions near the pigmentation genes tan and bric-à-brac 1, both corresponding to known cis-regulatory regions, which contain SNPs showing significant associations with pigmentation variation. While the Pool-GWAS approach suffers some limitations, its cost advantage facilitates replication and it can be applied to any non-model system with an available reference genome.
Population genetic theory shows that the efficacy of natural selection is limited by linkage-selection at one site interferes with selection at linked sites. Such interference slows adaptation in asexual genomes and may explain the evolutionary advantage of sex. Here, we test for two signatures of constraint caused by linkage in a sexual genome, by using sequence data from 255 Drosophila melanogaster and Drosophila simulans loci. We find that (i) the rate of protein adaptation is reduced in regions of low recombination, and (ii) evolution at strongly selected amino acid sites interferes with optimal codon usage at weakly selected, tightly linked synonymous sites. Together these findings suggest that linkage limits the rate and degree of adaptation even in recombining genomes. N atural selection is imperfect. To become fixed, beneficial mutations must overcome both stochastic loss and interference from selection at linked loci. In asexual genomes, where linkage is complete, two kinds of interference compromise adaptation. The first, ''ruby-in-the-rubbish'' interference, occurs because beneficial mutations often appear on genetic backgrounds loaded with segregating deleterious mutations. Since deleterious mutations are, on average, probably more strongly selected than favorable ones, adaptation is mostly limited to those lucky few beneficial mutations that arise on unloaded backgrounds (1-4). The second form of interference, ''clonal'' interference, is caused by competition among multiple segregating beneficial mutations (1, 5-7). Because only one asexual genome can be fixed at a time, adaptive substitutions are forced to be nearly sequential. Both kinds of interference limit the rate of adaptation in asexuals (8-10).The effects of both kinds of interference can be thought of as a reduction in the effective population size (N e ) caused by selection at linked loci (11-13). Recombination, by alleviating interference between linked sites, alleviates this reduction in N e . Consequently, genomic regions that differ in recombination rate also differ in effective size-indeed, this is the basis of the well-known correlation between recombination rate and levels of neutral polymorphism (4N e times the neutral mutation rate) seen in the genomes of Drosophila, humans, and others (14-18). That variation in linkage affects levels of neutral polymorphism suggests that it may also affect rates of nonneutral substitution. In particular, adaptive evolution may be limited in regions of low recombination (i.e., where N e is reduced) or in situations of extreme linkage (e.g., among sites within the same gene).Here we ask whether linkage systematically constrains adaptation in the Drosophila genome. We use divergence estimates from 255 Drosophila melanogaster and Drosophila simulans loci. These data are unique in that they include a large number of rapidly evolving genes, many of which are candidate male accessory gland proteins (Acps) and thus likely targets of sexual selection (19-21). We have reason to believe a priori not only t...
The P-element is one of the best understood eukaryotic transposable elements. It invaded Drosophila melanogaster populations within a few decades but was thought to be absent from close relatives, including Drosophila simulans. Five decades after the spread in D. melanogaster, we provide evidence that the P-element has also invaded D. simulans. P-elements in D. simulans appear to have been acquired recently from D. melanogaster probably via a single horizontal transfer event. Expression data indicate that the P-element is processed in the germ line of D. simulans, and genomic data show an enrichment of P-element insertions in putative origins of replication, similar to that seen in D. melanogaster. This ongoing spread of the P-element in natural populations provides a unique opportunity to understand the dynamics of transposable element spread and the associated piwi-interacting RNAs defense mechanisms.T he P-element, one of the best understood eukaryotic transposable elements (TEs), was originally discovered as the causal factor for a syndrome of abnormal phenotypes in Drosophila melanogaster. Crosses in which males derived from newly collected strains were mated with females from long established laboratory stocks produced offspring with spontaneous male recombination, high rates of sterility, and malformed gonadsthat is, "hybrid dysgenesis" (1-4). Eventually it was discovered that hybrid dysgenesis was due to the presence of a TE, the P-element (5, 6), which rapidly became the workhorse of Drosophila transgenesis (5, 7-9). Surveys of strains collected over 70 y show that the P-element spread rapidly in natural D. melanogaster populations, between 1950 and 1990 (10-12), and surveys of other Drosophila species revealed that the P-element had been horizontally transferred (HT) from a distantly related species, Drosophila willistoni (13). As there could be a considerable lag time between the initial transmission of a TE and its invasion of worldwide populations, it is unclear exactly when the P-element first entered D. melanogaster. However, the initial HT event likely occurred somewhere between the spread of D. melanogaster populations into the habitat of D. willistoni, around 1800 (14), and the onset of the worldwide invasion of D. melanogaster populations, around 1950 (10). In any case, the P-element had not been found in close relatives of D. melanogaster, including Drosophila simulans (13-18). The failure of the P-element to invade D. simulans is surprising, as both species are cosmopolitan, are mostly sympatric, and share insertions from many TE families via horizontal transfer (19,20). Furthermore, when artificially injected, the P-element can transpose in D. simulans, albeit at a reduced rate (21, 22). Results and DiscussionThe Recent Invasion of D. simulans Populations. Here, we show that the P-element has recently invaded natural D. simulans populations. We sequenced D. simulans collected from South Africa (in 2012) and from Florida (in 2010) as pools (Pool-seq) (23) and analyzed TE insertions in these ...
Genetic recombination associated with sexual reproduction is expected to have important consequences for the effectiveness of natural selection. These effects may be evident within genomes, in the form of contrasting patterns of molecular variation and evolution in regions with different levels of recombination. Previous work reveals patterns that are consistent with a benefit of recombination for adaptation at the level of protein sequence: both positive selection for adaptive variants and purifying selection against deleterious ones appear to be compromised in regions of low recombination [1-11]. Here, we re-examine these patterns by using polymorphism and divergence data from the Drosophila dot chromosome, which has a long history of reduced recombination. To avoid confounding selection and demographic effects, we collected these data from a species with an apparently stable demographic history, Drosophila americana. We find that D. americana dot loci show several signatures of ineffective purifying and positive selection, including an increase in the rate of protein evolution, an increase in protein polymorphism, and a reduction in the proportion of amino acid substitutions attributable to positive selection.
Around the new or full moon, during a few specific hours surrounding low tide, millions of non-biting midges of the species C. marinus emerge from the sea to perform their nuptial dance. Adults live for only a few hours, during which they mate and oviposit. They must therefore emerge synchronously and-given that embryonic, larval and pupal development take place in the sea-at a time when the most extreme tides reliably expose the larval habitat. The lowest low tides occur predictably during specific days of the lunar month at a specific time of day. Consequently, adult emergence in C. marinus is under the control of circalunar and circadian clocks 1,2 . Notably, although the lowest low tides recur invariably at a given location, their timing differs between geographic locations 3 . Consequently, C. marinus strains from different locations (Extended Data Fig. 1a) show local adaptation in circadian and circalunar emergence times (Extended Data Fig. 1b, c). Crosses between the Jean and Por strains showed that the differences in circadian and circalunar timing are genetically determined 4,5 and largely explained by two circadian and two circalunar quantitative trait loci (QTLs) 6 . Studies on timing variation or chronotypes in animals and humans have often focused on candidate genes from the circadian transcriptiontranslational oscillator. In D. melanogaster, polymorphisms in the core circadian clock genes period, timeless and cryptochrome are associated with adaptive differences in temperature compensation 7 , photo-responsiveness of the circadian clock 8 and emergence rhythms 9 . While these studies offer insights into the evolution of known circadianclock molecules, genome-wide association studies 10,11 and other forward genetic approaches (reviewed in ref. 12) are essential to provide a comprehensive, unbiased assessment of natural timing variation, for instance underlying human sleep-phase disorders. While the adaptive nature of human chronotypes remains unclear, the chronotypes of C. marinus represent evolutionary adaptations to their habitat.Our study aimed to identify the genetic basis of C. marinus adaptation to its specific ecological 'timing niche' . In addition, the genetic dissection of adaptive natural variants of non-circadian rhythms 13 , as also present in C. marinus, may provide an entry point into their unknown molecular mechanisms.As a starting point for these analyses, we sequenced, assembled, mapped and annotated a C. marinus reference genome. The Clunio genome and QTLs for timingOur reference genome CLUMA_1.0 of the Jean laboratory strain contained 85.6 Mb of sequence (Table 1), close to the previous flowcytometry-based estimate of 95 Mb 6 , underlining that chironomids generally have small genomes [14][15][16] . The final assembly has a scaffold N50 of 1.9 Mb. Genome-wide genotyping of a mapping family with restriction-site associated DNA sequencing allowed 92% of the reference sequence to be consistently anchored along a genetic linkage map (Fig. 1a and Extended Data Fig. 2 Table 2). The C. ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.