publications

2025

1. 

   Consequences of drive on the evolution of genomes and species

   Logan T Edvalson and Amanda M Larracuente

   G3: Genes, Genomes, Genetics, Jun 2025

   Publisher: Oxford University Press (OUP)

   Abs DOI

   Meiotic drivers violate Mendelian principles by biasing their segregation to the next generation, often at a cost to the individual. This cost leads to a cyclical arms race between drivers and host genomes where drivers acquire modifications to cheat, and the rest of the genome evolves counter-drive mechanisms to restore fair segregation. Repeated bouts of innovation on both sides of the conflict can have consequences for genome and species evolution. Much of the foundational and recent work in this field has found its home in the Genetics Society of America journals. In this commentary, Edvalson and Larracuente highlight some recent work published in these journals that address key questions about the evolutionary consequences of meiotic drive.

2. 

   An innovation in host responses to escalating genomic conflicts

   Emiliano Martí and Amanda M. Larracuente

   Trends in Genetics, May 2025

   Publisher: Elsevier BV

   DOI

3. 

   Seeing the Forest Despite the Trees in Repeat‐Rich Genomic Regions

   Amanda M. Larracuente and John S. Sproul

   Molecular Ecology Resources, Jul 2025

   Publisher: Wiley

   DOI

2024

1. 

   Turnover of retroelements and satellite DNA drives centromere reorganization over short evolutionary timescales in Drosophila

   Cécile Courret, Lucas W. Hemmer, Xiaolu Wei, and 7 more authors

   PLOS Biology, Nov 2024

   Publisher: Public Library of Science (PLoS)

   Abs DOI

   Centromeres reside in rapidly evolving, repeat-rich genomic regions, despite their essential function in chromosome segregation. Across organisms, centromeres are rich in selfish genetic elements such as transposable elements and satellite DNAs that can bias their transmission through meiosis. However, these elements still need to cooperate at some level and contribute to, or avoid interfering with, centromere function. To gain insight into the balance between conflict and cooperation at centromeric DNA, we take advantage of the close evolutionary relationships within the Drosophila simulans clade—D. simulans, D. sechellia, and D. mauritiana—and their relative, D. melanogaster. Using chromatin profiling combined with high-resolution fluorescence in situ hybridization on stretched chromatin fibers, we characterize all centromeres across these species. We discovered dramatic centromere reorganization involving recurrent shifts between retroelements and satellite DNAs over short evolutionary timescales. We also reveal the recent origin (\textless240 Kya) of telocentric chromosomes in D. sechellia, where the X and fourth centromeres now sit on telomere-specific retroelements. Finally, the Y chromosome centromeres, which are the only chromosomes that do not experience female meiosis, do not show dynamic cycling between satDNA and TEs. The patterns of rapid centromere turnover in these species are consistent with genetic conflicts in the female germline and have implications for centromeric DNA function and karyotype evolution. Regardless of the evolutionary forces driving this turnover, the rapid reorganization of centromeric sequences over short evolutionary timescales highlights their potential as hotspots for evolutionary innovation.

2. 

   Transcription of a centromere-enriched retroelement and local retention of its RNA are significant features of the CENP-A chromatin landscape

   B. J. Chabot, R. Sun, A. Amjad, and 9 more authors

   Genome Biology, Nov 2024

   Publisher: Springer Science and Business Media LLC

   DOI

2023

1. High levels of intra-strain structural variation in \textitDrosophila simulans X pericentric heterochromatin

   Cécile Courret and Amanda M Larracuente

   GENETICS, Dec 2023

   Publisher: Oxford University Press (OUP)

   Abs DOI

   Abstract Large genome structural variations can impact genome regulation and integrity. Repeat-rich regions like pericentric heterochromatin are vulnerable to structural rearrangements although we know little about how often these rearrangements occur over evolutionary time. Repetitive genome regions are particularly difficult to study with genomic approaches, as they are missing from most genome assemblies. However, cytogenetic approaches offer a direct way to detect large rearrangements involving pericentric heterochromatin. Here, we use a cytogenetic approach to reveal large structural rearrangements associated with the X pericentromeric region of Drosophila simulans. These rearrangements involve large blocks of satellite DNA—the 500-bp and Rsp-like satellites—which colocalize in the X pericentromeric heterochromatin. We find that this region is polymorphic not only among different strains, but between isolates of the same strain from different labs, and even within individual isolates. On the one hand, our observations raise questions regarding the potential impact of such variation at the phenotypic level and our ability to control for such genetic variability. On the other hand, this highlights the very rapid turnover of the pericentric heterochromatin most likely associated with genomic instability of the X pericentromere. It represents a unique opportunity to study the dynamics of pericentric heterochromatin, the evolution of associated satellites on a very short time scale, and to better understand how structural variation arises.

2. New perspectives on the causes and consequences of male meiotic drive

   Cécile Courret, Xiaolu Wei, and Amanda M Larracuente

   Current Opinion in Genetics & Development, Dec 2023

   Publisher: Elsevier BV

   DOI
3. Meeting report: transposable elements at the crossroads of evolution, health and disease 2023

   Irina R. Arkhipova, Kathleen H. Burns, Katherine B. Chiappinelli, and 6 more authors

   Mobile DNA, Nov 2023

   Publisher: Springer Science and Business Media LLC

   Abs DOI

   AbstractThe conference “Transposable Elements at the Crossroads of Evolution, Health and Disease” was hosted by Keystone Symposia in Whistler, British Columbia, Canada, on September 3–6, 2023, and was organized by Kathleen Burns, Harmit Malik and Irina Arkhipova. The central theme of the meeting was the incredible diversity of ways in which transposable elements (TEs) interact with the host, from disrupting the existing genes and pathways to creating novel gene products and expression patterns, enhancing the repertoire of host functions, and ultimately driving host evolution. The meeting was organized into six plenary sessions and two afternoon workshops with a total of 50 invited and contributed talks, two poster sessions, and a career roundtable. The topics ranged from TE roles in normal and pathological processes to restricting and harnessing TE activity based on mechanistic insights gained from genetic, structural, and biochemical studies.

4. Genetic conflict and the origin of multigene families: implications for sex chromosome evolution

   Emiliano Martí and Amanda M. Larracuente

   Proceedings of the Royal Society B: Biological Sciences, Nov 2023

   Publisher: The Royal Society

   Abs DOI

   Sex chromosomes are havens for intragenomic conflicts. The absence of recombination between sex chromosomes creates the opportunity for the evolution of segregation distorters: selfish genetic elements that hijack different aspects of an individual’s reproduction to increase their own transmission. Biased (non-Mendelian) segregation, however, often occurs at a detriment to their host’s fitness, and therefore can trigger evolutionary arms races that can have major consequences for genome structure and regulation, gametogenesis, reproductive strategies and even speciation. Here, we review an emerging feature from comparative genomic and sex chromosome evolution studies suggesting that meiotic drive is pervasive: the recurrent evolution of paralogous sex-linked gene families. Sex chromosomes of several species independently acquire and co-amplify rapidly evolving gene families with spermatogenesis-related functions, consistent with a history of intragenomic conflict over transmission. We discuss Y chromosome features that might contribute to the tempo and mode of evolution of X/Y co-amplified gene families, as well as their implications for the evolution of complexity in the genome. Finally, we propose a framework that explores the conditions that might allow for recurrent bouts of fixation of drivers and suppressors, in a dosage-sensitive fashion, and therefore the co-amplification of multigene families on sex chromosomes.

5. The Evolutionary History of \textitDrosophila simulans Y Chromosomes Reveals Molecular Signatures of Resistance to Sex Ratio Meiotic Drive

   Cécile Courret, David Ogereau, Clément Gilbert, and 2 more authors

   Molecular Biology and Evolution, Jul 2023

   Publisher: Oxford University Press (OUP)

   Abs DOI

   Abstract The recent evolutionary history of the Y chromosome in Drosophila simulans, a worldwide species of Afrotropical origin, is closely linked to that of X-linked meiotic drivers (Paris system). The spread of the Paris drivers in natural populations has elicited the selection of drive-resistant Y chromosomes. To infer the evolutionary history of the Y chromosome in relation to the Paris drive, we sequenced 21 iso-Y lines, each carrying a Y chromosome from a different location. Among them, 13 lines carry a Y chromosome that is able to counteract the effect of the drivers. Despite their very different geographical origins, all sensitive Y’s are highly similar, suggesting that they share a recent common ancestor. The resistant Y chromosomes are more divergent and segregate in four distinct clusters. The phylogeny of the Y chromosome confirms that the resistant lineage predates the emergence of Paris drive. The ancestry of the resistant lineage is further supported by the examination of Y-linked sequences in the sister species of D. simulans, Drosophila sechellia and Drosophila mauritiana. We also characterized the variation in repeat content among Y chromosomes and identified multiple simple satellites associated with resistance. Altogether, the molecular polymorphism allows us to infer the demographic and evolutionary history of the Y chromosome and provides new insights on the genetic basis of resistance.

6. Analyses of 600+ insect genomes reveal repetitive element dynamics and highlight biodiversity-scale repeat annotation challenges

   John S. Sproul, Scott Hotaling, Jacqueline Heckenhauer, and 6 more authors

   Genome Research, Oct 2023

   Publisher: Cold Spring Harbor Laboratory

   Abs DOI

   Repetitive elements (REs) are integral to the composition, structure, and function of eukaryotic genomes, yet remain understudied in most taxonomic groups. We investigated REs across 601 insect species and report wide variation in RE dynamics across groups. Analysis of associations between REs and protein-coding genes revealed dynamic evolution at the interface between REs and coding regions across insects, including notably elevated RE–gene associations in lineages with abundant long interspersed nuclear elements (LINEs). We leveraged this large, empirical data set to quantify impacts of long-read technology on RE detection and investigate fundamental challenges to RE annotation in diverse groups. In long-read assemblies, we detected ∼36% more REs than short-read assemblies, with long terminal repeats (LTRs) showing 162% increased detection, whereas DNA transposons and LINEs showed less respective technology-related bias. In most insect lineages, 25%–85% of repetitive sequences were “unclassified” following automated annotation, compared with only ∼13% inDrosophilaspecies. Although the diversity of available insect genomes has rapidly expanded, we show the rate of community contributions to RE databases has not kept pace, preventing efficient annotation and high-resolution study of REs in most groups. We highlight the tremendous opportunity and need for the biodiversity genomics field to embrace REs and suggest collective steps for making progress toward this goal.

2022

1. Centromere-associated retroelement evolution in\textitDrosophila melanogasterreveals an underlying conflict

   Lucas W. Hemmer, Sherif Negm, Xuewen Geng, and 8 more authors

   Nov 2022

   Abs DOI

   ABSTRACTCentromeres are chromosomal regions essential for coordinating chromosome segregation during cell division. While centromeres are defined by the presence of a centromere-specific histone H3 variant rather than a particular DNA sequence, they are typically embedded in repeat-dense chromosomal genome regions. In many species, centromeres are associated with transposable elements, but it is unclear if these elements are selfish or if they play a role in centromere specification or function. Here we useDrosophila melanogasteras a model to understand the evolution of centromere-associated transposable elements.G2/Jockey-3is a non-LTR retroelement in theJockeyclade and the only sequence shared by all centromeres. We study the evolution ofG2/Jockey-3using short and long read population genomic data to infer insertion polymorphisms across the genome. We combine estimates of the age, frequency, and location of insertions to infer the evolutionary processes shapingG2/Jockey-3and its association with the centromeres. We find thatG2/Jockey-3is an active retroelement targeted by the piRNA pathway that is enriched in centromeres at least in part due to an insertion bias. We do not detect signatures of positive selection on anyG2/Jockey-3insertions that would suggest than individual copies are favored by natural selection. Instead, we infer that most insertions are neutral or weakly deleterious both inside and outside of the centromeres. Therefore,G2/Jockey-3evolution is consistent with it being a selfish genetic element that targets centromeres. We propose that targeting centromeres helps active retroelements escape host defenses, as the unique centromeric chromatin may prevent targeting by the host silencing machinery. At the same time, centromeric TEs insertions may be tolerated or even beneficial if they also contribute to the transcriptional and chromatin environment. Thus, we suspect centromere-associated retroelements likeG2/Jockey-3reflect a balance between conflict and cooperation at the centromeres.

2. When it comes to genetics, cheaters do prosper

   Stacey L. Hanlon and Amanda M. Larracuente

   Chromosome Research, Sep 2022

   Publisher: Springer Science and Business Media LLC

   DOI
3. Epistatic selection on a selfish Segregation Distorter supergene – drive, recombination, and genetic load

   Beatriz Navarro-Dominguez, Ching-Ho Chang, Cara L Brand, and 3 more authors

   eLife, Apr 2022

   Publisher: eLife Sciences Publications, Ltd

   Abs DOI

   Meiotic drive supergenes are complexes of alleles at linked loci that together subvert Mendelian segregation resulting in preferential transmission. In males, the most common mechanism of drive involves the disruption of sperm bearing one of a pair of alternative alleles. While at least two loci are important for male drive—the driver and the target—linked modifiers can enhance drive, creating selection pressure to suppress recombination. In this work, we investigate the evolution and genomic consequences of an autosomal, multilocus, male meiotic drive system, Segregation Distorter (SD) in the fruit fly, Drosophila melanogaster. In African populations, the predominant SD chromosome variant, SD-Mal, is characterized by two overlapping, paracentric inversions on chromosome arm 2R and nearly perfect (~100%) transmission. We study the SD-Mal system in detail, exploring its components, chromosomal structure, and evolutionary history. Our findings reveal a recent chromosome-scale selective sweep mediated by strong epistatic selection for haplotypes carrying Sd, the main driving allele, and one or more factors within the double inversion. While most SD-Mal chromosomes are homozygous lethal, SD-Mal haplotypes can recombine with other, complementing haplotypes via crossing over, and with wildtype chromosomes via gene conversion. SD-Mal chromosomes have nevertheless accumulated lethal mutations, excess non-synonymous mutations, and excess transposable element insertions. Therefore, SD-Mal haplotypes evolve as a small, semi-isolated subpopulation with a history of strong selection. These results may explain the evolutionary turnover of SD haplotypes in different populations around the world and have implications for supergene evolution broadly.

4. The nanoCUT&RUN technique visualizes telomeric chromatin in Drosophila

   Tao Chen, Xiaolu Wei, Cécile Courret, and 6 more authors

   PLOS Genetics, Sep 2022

   Publisher: Public Library of Science (PLoS)

   Abs DOI

   Advances in genomic technology led to a more focused pattern for the distribution of chromosomal proteins and a better understanding of their functions. The recent development of the CUT&RUN technique marks one of the important such advances. Here we develop a modified CUT&RUN technique that we termed nanoCUT&RUN, in which a high affinity nanobody to GFP is used to bring micrococcal nuclease to the binding sites of GFP-tagged chromatin proteins. Subsequent activation of the nuclease cleaves the chromatin, and sequencing of released DNA identifies binding sites. We show that nanoCUT&RUN efficiently produces high quality data for the TRL transcription factor in Drosophila embryos, and distinguishes binding sites specific between two TRL isoforms. We further show that nanoCUT&RUN dissects the distributions of the HipHop and HOAP telomere capping proteins, and uncovers unexpected binding of telomeric proteins at centromeres. nanoCUT&RUN can be readily applied to any system in which a chromatin protein of interest, or its isoforms, carries the GFP tag.

5. Unique structure and positive selection promote the rapid divergence of Drosophila Y chromosomes

   Ching-Ho Chang, Lauren E Gregory, Kathleen E Gordon, and 2 more authors

   eLife, Jan 2022

   Publisher: eLife Sciences Publications, Ltd

   Abs DOI

   Y chromosomes across diverse species convergently evolve a gene-poor, heterochromatic organization enriched for duplicated genes, LTR retrotransposons, and satellite DNA. Sexual antagonism and a loss of recombination play major roles in the degeneration of young Y chromosomes. However, the processes shaping the evolution of mature, already degenerated Y chromosomes are less well-understood. Because Y chromosomes evolve rapidly, comparisons between closely related species are particularly useful. We generated de novo long-read assemblies complemented with cytological validation to reveal Y chromosome organization in three closely related species of the Drosophila simulans complex, which diverged only 250,000 years ago and share \textgreater98% sequence identity. We find these Y chromosomes are divergent in their organization and repetitive DNA composition and discover new Y-linked gene families whose evolution is driven by both positive selection and gene conversion. These Y chromosomes are also enriched for large deletions, suggesting that the repair of double-strand breaks on Y chromosomes may be biased toward microhomology-mediated end joining over canonical non-homologous end-joining. We propose that this repair mechanism contributes to the convergent evolution of Y chromosome organization across organisms.

6. Genome size evolution in the diverse insect order Trichoptera

   Jacqueline Heckenhauer, Paul B Frandsen, John S Sproul, and 8 more authors

   GigaScience, Feb 2022

   Publisher: Oxford University Press (OUP)

   Abs DOI

   Abstract Background Genome size is implicated in the form, function, and ecological success of a species. Two principally different mechanisms are proposed as major drivers of eukaryotic genome evolution and diversity: polyploidy (i.e., whole-genome duplication) or smaller duplication events and bursts in the activity of repetitive elements. Here, we generated de novo genome assemblies of 17 caddisflies covering all major lineages of Trichoptera. Using these and previously sequenced genomes, we use caddisflies as a model for understanding genome size evolution in diverse insect lineages. Results We detect a ∼14-fold variation in genome size across the order Trichoptera. We find strong evidence that repetitive element expansions, particularly those of transposable elements (TEs), are important drivers of large caddisfly genome sizes. Using an innovative method to examine TEs associated with universal single-copy orthologs (i.e., BUSCO genes), we find that TE expansions have a major impact on protein-coding gene regions, with TE-gene associations showing a linear relationship with increasing genome size. Intriguingly, we find that expanded genomes preferentially evolved in caddisfly clades with a higher ecological diversity (i.e., various feeding modes, diversification in variable, less stable environments). Conclusion Our findings provide a platform to test hypotheses about the potential evolutionary roles of TE activity and TE-gene associations, particularly in groups with high species, ecological, and functional diversities.

2021

1. Heterochromatin-dependent transcription of satellite DNAs in the Drosophila melanogaster female germline

   Xiaolu Wei, Danna G Eickbush, Iain Speece, and 1 more author

   eLife, Jul 2021

   Publisher: eLife Sciences Publications, Ltd

   Abs DOI

   Large blocks of tandemly repeated DNAs—satellite DNAs (satDNAs)—play important roles in heterochromatin formation and chromosome segregation. We know little about how satDNAs are regulated; however, their misregulation is associated with genomic instability and human diseases. We use the Drosophila melanogaster germline as a model to study the regulation of satDNA transcription and chromatin. Here we show that complex satDNAs (\textgreater100-bp repeat units) are transcribed into long noncoding RNAs and processed into piRNAs (PIWI interacting RNAs). This satDNA piRNA production depends on the Rhino-Deadlock-Cutoff complex and the transcription factor Moonshiner—a previously described non-canonical pathway that licenses heterochromatin-dependent transcription of dual-strand piRNA clusters. We show that this pathway is important for establishing heterochromatin at satDNAs. Therefore, satDNAs are regulated by piRNAs originating from their own genomic loci. This novel mechanism of satDNA regulation provides insight into the role of piRNA pathways in heterochromatin formation and genome stability.

2. Distinct spermiogenic phenotypes underlie sperm elimination in the Segregation Distorter meiotic drive system

   Marion Herbette, Xiaolu Wei, Ching-Ho Chang, and 3 more authors

   PLOS Genetics, Jul 2021

   Publisher: Public Library of Science (PLoS)

   Abs DOI

   Segregation Distorter (SD) is a male meiotic drive system in Drosophila melanogaster. Males heterozygous for a selfish SD chromosome rarely transmit the homologous SD+ chromosome. It is well established that distortion results from an interaction between Sd, the primary distorting locus on the SD chromosome and its target, a satellite DNA called Rsp, on the SD+ chromosome. However, the molecular and cellular mechanisms leading to post-meiotic SD+ sperm elimination remain unclear. Here we show that SD/SD+ males of different genotypes but with similarly strong degrees of distortion have distinct spermiogenic phenotypes. In some genotypes, SD+ spermatids fail to fully incorporate protamines after the removal of histones, and degenerate during the individualization stage of spermiogenesis. In contrast, in other SD/SD+ genotypes, protamine incorporation appears less disturbed, yet spermatid nuclei are abnormally compacted, and mature sperm nuclei are eventually released in the seminal vesicle. Our analyses of different SD+ chromosomes suggest that the severity of the spermiogenic defects associates with the copy number of the Rsp satellite. We propose that when Rsp copy number is very high (\textgreater 2000), spermatid nuclear compaction defects reach a threshold that triggers a checkpoint controlling sperm chromatin quality to eliminate abnormal spermatids during individualization.

3. Long Reads Are Revolutionizing 20 Years of Insect Genome Sequencing

   Scott Hotaling, John S Sproul, Jacqueline Heckenhauer, and 5 more authors

   Genome Biology and Evolution, Aug 2021

   Publisher: Oxford University Press (OUP)

   Abs DOI

   Abstract The first insect genome assembly (Drosophila melanogaster) was published two decades ago. Today, nuclear genome assemblies are available for a staggering 601 insect species representing 20 orders. In this study, we analyzed the most-contiguous assembly for each species and provide a “state-of-the-field” perspective, emphasizing taxonomic representation, assembly quality, gene completeness, and sequencing technologies. Relative to species richness, genomic efforts have been biased toward four orders (Diptera, Hymenoptera, Collembola, and Phasmatodea), Coleoptera are underrepresented, and 11 orders still lack a publicly available genome assembly. The average insect genome assembly is 439.2 Mb in length with 87.5% of single-copy benchmarking genes intact. Most notable has been the impact of long-read sequencing; assemblies that incorporate long reads are ∼48× more contiguous than those that do not. We offer four recommendations as we collectively continue building insect genome resources: 1) seek better integration between independent research groups and consortia, 2) balance future sampling between filling taxonomic gaps and generating data for targeted questions, 3) take advantage of long-read sequencing technologies, and 4) expand and improve gene annotations.

4. Evolution of genome structure in the\textitDrosophila simulansspecies complex

   Mahul Chakraborty, Ching-Ho Chang, Danielle E. Khost, and 7 more authors

   Genome Research, Mar 2021

   Publisher: Cold Spring Harbor Laboratory

   Abs DOI

   The rapid evolution of repetitive DNA sequences, including satellite DNA, tandem duplications, and transposable elements, underlies phenotypic evolution and contributes to hybrid incompatibilities between species. However, repetitive genomic regions are fragmented and misassembled in most contemporary genome assemblies. We generated highly contiguous de novo reference genomes for theDrosophila simulansspecies complex (D. simulans,D. mauritiana, andD. sechellia), which speciated ∼250,000 yr ago. Our assemblies are comparable in contiguity and accuracy to the currentD. melanogastergenome, allowing us to directly compare repetitive sequences between these four species. We find that at least 15% of theD. simulanscomplex species genomes fail to align uniquely toD. melanogasterowing to structural divergence—twice the number of single-nucleotide substitutions. We also find rapid turnover of satellite DNA and extensive structural divergence in heterochromatic regions, whereas the euchromatic gene content is mostly conserved. Despite the overall preservation of gene synteny, euchromatin in each species has been shaped by clade- and species-specific inversions, transposable elements, expansions and contractions of satellite and tRNA tandem arrays, and gene duplications. We also find rapid divergence among Y-linked genes, including copy number variation and recent gene duplications from autosomes. Our assemblies provide a valuable resource for studying genome evolution and its consequences for phenotypic evolution in these genetic model species.

5. RepeatProfiler: A pipeline for visualization and comparative analysis of repetitive DNA profiles

   Sherif Negm, Anya Greenberg, Amanda M. Larracuente, and 1 more author

   Molecular Ecology Resources, Apr 2021

   Publisher: Wiley

   Abs DOI

   AbstractStudy of repetitive DNA elements in model organisms highlights the role of repetitive elements (REs) in many processes that drive genome evolution and phenotypic change. Because REs are much more dynamic than single‐copy DNA, repetitive sequences can reveal signals of evolutionary history over short time scales that may not be evident in sequences from slower‐evolving genomic regions. Many tools for studying REs are directed toward organisms with existing genomic resources, including genome assemblies and repeat libraries. However, signals in repeat variation may prove especially valuable in disentangling evolutionary histories in diverse non‐model groups, for which genomic resources are limited. Here, we introduce RepeatProfiler, a tool for generating, visualizing, and comparing repetitive element DNA profiles from low‐coverage, short‐read sequence data. RepeatProfiler automates the generation and visualization of RE coverage depth profiles (RE profiles) and allows for statistical comparison of profile shape across samples. In addition, RepeatProfiler facilitates comparison of profiles by extracting signal from sequence variants across profiles which can then be analysed as molecular morphological characters using phylogenetic analysis. We validate RepeatProfiler with data sets from ground beetles (Bembidion), flies (Drosophila), and tomatoes (Solanum). We highlight the potential of RE profiles as a high‐resolution data source for studies in species delimitation, comparative genomics, and repeat biology.

2020

1. Resistance to natural and synthetic gene drive systems

   Tom A. R. Price, Nikolai Windbichler, Robert L. Unckless, and 18 more authors

   Journal of Evolutionary Biology, Oct 2020

   Publisher: Oxford University Press (OUP)

   Abs DOI

   AbstractScientists are rapidly developing synthetic gene drive elements intended for release into natural populations. These are intended to control or eradicate disease vectors and pests, or to spread useful traits through wild populations for disease control or conservation purposes. However, a crucial problem for gene drives is the evolution of resistance against them, preventing their spread. Understanding the mechanisms by which populations might evolve resistance is essential for engineering effective gene drive systems. This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in general.

2. Dynamic Evolution of Euchromatic Satellites on the X Chromosome in Drosophila melanogaster and the simulans Clade

   John S Sproul, Danielle E Khost, Danna G Eickbush, and 4 more authors

   Molecular Biology and Evolution, Aug 2020

   Publisher: Oxford University Press (OUP)

   Abs DOI

   AbstractSatellite DNAs (satDNAs) are among the most dynamically evolving components of eukaryotic genomes and play important roles in genome regulation, genome evolution, and speciation. Despite their abundance and functional impact, we know little about the evolutionary dynamics and molecular mechanisms that shape satDNA distributions in genomes. Here, we use high-quality genome assemblies to study the evolutionary dynamics of two complex satDNAs, Rsp-like and 1.688 g/cm3, in Drosophila melanogaster and its three nearest relatives in the simulans clade. We show that large blocks of these repeats are highly dynamic in the heterochromatin, where their genomic location varies across species. We discovered that small blocks of satDNA that are abundant in X chromosome euchromatin are similarly dynamic, with repeats changing in abundance, location, and composition among species. We detail the proliferation of a rare satellite (Rsp-like) across the X chromosome in D. simulans and D. mauritiana. Rsp-like spread by inserting into existing clusters of the older, more abundant 1.688 satellite, in events likely facilitated by microhomology-mediated repair pathways. We show that Rsp-like is abundant on extrachromosomal circular DNA in D. simulans, which may have contributed to its dynamic evolution. Intralocus satDNA expansions via unequal exchange and the movement of higher order repeats also contribute to the fluidity of the repeat landscape. We find evidence that euchromatic satDNA repeats experience cycles of proliferation and diversification somewhat analogous to bursts of transposable element proliferation. Our study lays a foundation for mechanistic studies of satDNA proliferation and the functional and evolutionary consequences of satDNA movement.

2019

1. Meiotic drive mechanisms: lessons from\textitDrosophila

   Cécile Courret, Ching-Ho Chang, Kevin H.-C. Wei, and 2 more authors

   Proceedings of the Royal Society B: Biological Sciences, Oct 2019

   Publisher: The Royal Society

   Abs DOI

   Meiotic drivers are selfish genetic elements that bias their transmission into gametes, often to the detriment of the rest of the genome. The resulting intragenomic conflicts triggered by meiotic drive create evolutionary arms races and shape genome evolution. The phenomenon of meiotic drive is widespread across taxa but is particularly prominent in theDrosophilagenus. Recent studies inDrosophilahave provided insights into the genetic origins of drivers and their molecular mechanisms. Here, we review the current literature on mechanisms of drive with an emphasis on sperm killers inDrosophilaspecies. In these systems, meiotic drivers often evolve from gene duplications and targets are generally linked to heterochromatin. While dense in repetitive elements and difficult to study using traditional genetic and genomic approaches, recent work inDrosophilahas made progress on the heterochromatic compartment of the genome. Although we still understand little about precise drive mechanisms, studies of male drive systems are converging on common themes such as heterochromatin regulation, small RNA pathways, and nuclear transport pathways. Meiotic drive systems are therefore promising models for discovering fundamental features of gametogenesis.

2. Islands of retroelements are major components of Drosophila centromeres

   Ching-Ho Chang, Ankita Chavan, Jason Palladino, and 9 more authors

   PLOS Biology, May 2019

   Publisher: Public Library of Science (PLoS)

   DOI
3. Heterochromatin-Enriched Assemblies Reveal the Sequence and Organization of the\textitDrosophila melanogasterY Chromosome

   Ching-Ho Chang and Amanda M Larracuente

   Genetics, Jan 2019

   Publisher: Oxford University Press (OUP)

   Abs DOI

   AbstractHeterochromatic repeat-rich regions are often missing from even the best genome assemblies. Chang and Larracuente designed a de novo assembly strategy to improve the Drosophila melanogaster assembly in heterochromatin, extending the reference assembly by 11.9 Mb, including 10.6 Mb from the Y chromosome.....Heterochromatic regions of the genome are repeat-rich and poor in protein coding genes, and are therefore underrepresented in even the best genome assemblies. One of the most difficult regions of the genome to assemble are sex-limited chromosomes. The Drosophila melanogaster Y chromosome is entirely heterochromatic, yet has wide-ranging effects on male fertility, fitness, and genome-wide gene expression. The genetic basis of this phenotypic variation is difficult to study, in part because we do not know the detailed organization of the Y chromosome. To study Y chromosome organization in D. melanogaster, we develop an assembly strategy involving the in silico enrichment of heterochromatic long single-molecule reads and use these reads to create targeted de novo assemblies of heterochromatic sequences. We assigned contigs to the Y chromosome using Illumina reads to identify male-specific sequences. Our pipeline extends the D. melanogaster reference genome by 11.9 Mb, closes 43.8% of the gaps, and improves overall contiguity. The addition of 10.6 MB of Y-linked sequence permitted us to study the organization of repeats and genes along the Y chromosome. We detected a high rate of duplication to the pericentric regions of the Y chromosome from other regions in the genome. Most of these duplicated genes exist in multiple copies. We detail the evolutionary history of one sex-linked gene family, crystal-Stellate. While the Y chromosome does not undergo crossing over, we observed high gene conversion rates within and between members of the crystal-Stellate gene family, Su(Ste), and PCKR, compared to genome-wide estimates. Our results suggest that gene conversion and gene duplication play an important role in the evolution of Y-linked genes.

2018

1. Firefly genomes illuminate parallel origins of bioluminescence in beetles

   Timothy R Fallon, Sarah E Lower, Ching-Ho Chang, and 19 more authors

   eLife, Oct 2018

   Publisher: eLife Sciences Publications, Ltd

   Abs DOI

   Fireflies and their luminous courtships have inspired centuries of scientific study. Today firefly luciferase is widely used in biotechnology, but the evolutionary origin of bioluminescence within beetles remains unclear. To shed light on this long-standing question, we sequenced the genomes of two firefly species that diverged over 100 million-years-ago: the North AmericanPhotinus pyralisand JapaneseAquatica lateralis.To compare bioluminescent origins, we also sequenced the genome of a related click beetle, the CaribbeanIgnelater luminosus, with bioluminescent biochemistry near-identical to fireflies, but anatomically unique light organs, suggesting the intriguing hypothesis of parallel gains of bioluminescence. Our analyses support independent gains of bioluminescence in fireflies and click beetles, and provide new insights into the genes, chemical defenses, and symbionts that evolved alongside their luminous lifestyle.

2017

1. Single-molecule sequencing resolves the detailed structure of complex satellite DNA loci in \textitDrosophila melanogaster

   Daniel E. Khost, Danna G. Eickbush, and Amanda M. Larracuente

   Genome Research, May 2017

   Publisher: Cold Spring Harbor Laboratory

   Abs DOI

   Highly repetitive satellite DNA (satDNA) repeats are found in most eukaryotic genomes. SatDNAs are rapidly evolving and have roles in genome stability and chromosome segregation. Their repetitive nature poses a challenge for genome assembly and makes progress on the detailed study of satDNA structure difficult. Here, we use single-molecule sequencing long reads from Pacific Biosciences (PacBio) to determine the detailed structure of all major autosomal complex satDNA loci in Drosophila melanogaster, with a particular focus on the 260-bp and Responder satellites. We determine the optimal de novo assembly methods and parameter combinations required to produce a high-quality assembly of these previously unassembled satDNA loci and validate this assembly using molecular and computational approaches. We determined that the computationally intensive PBcR-BLASR assembly pipeline yielded better assemblies than the faster and more efficient pipelines based on the MHAP hashing algorithm, and it is essential to validate assemblies of repetitive loci. The assemblies reveal that satDNA repeats are organized into large arrays interrupted by transposable elements. The repeats in the center of the array tend to be homogenized in sequence, suggesting that gene conversion and unequal crossovers lead to repeat homogenization through concerted evolution, although the degree of unequal crossing over may differ among complex satellite loci. We find evidence for higher-order structure within satDNA arrays that suggest recent structural rearrangements. These assemblies provide a platform for the evolutionary and functional genomics of satDNAs in pericentric heterochromatin.

2. Genomic changes following the reversal of a Y chromosome to an autosome in\textitDrosophila pseudoobscura: Y CHROMOSOME REVERSAL IN\textitDROSOPHILA PSEUDOOBSCURA

   Ching-Ho Chang and Amanda M. Larracuente

   Evolution, May 2017

   Publisher: Wiley

   DOI

2016

1. Host–Symbiont Interactions: Male-Killers Exposed

   Amanda M. Larracuente and Victoria H. Meller

   Current Biology, May 2016

   Publisher: Elsevier BV

   DOI
2. The Ecology and Evolutionary Dynamics of Meiotic Drive

   Anna K. Lindholm, Kelly A. Dyer, Renée C. Firman, and 19 more authors

   Trends in Ecology & Evolution, Apr 2016

   Publisher: Elsevier BV

   DOI

2015

1. Genetics on the Fly: A Primer on the\textitDrosophilaModel System

   Karen G Hales, Christopher A Korey, Amanda M Larracuente, and 1 more author

   Genetics, Nov 2015

   Publisher: Oxford University Press (OUP)

   Abs DOI

   AbstractFruit flies of the genus Drosophila have been an attractive and effective genetic model organism since Thomas Hunt Morgan and colleagues made seminal discoveries with them a century ago. Work with Drosophila has enabled dramatic advances in cell and developmental biology, neurobiology and behavior, molecular biology, evolutionary and population genetics, and other fields. With more tissue types and observable behaviors than in other short-generation model organisms, and with vast genome data available for many species within the genus, the fly’s tractable complexity will continue to enable exciting opportunities to explore mechanisms of complex developmental programs, behaviors, and broader evolutionary questions. This primer describes the organism’s natural history, the features of sequenced genomes within the genus, the wide range of available genetic tools and online resources, the types of biological questions Drosophila can help address, and historical milestones.

2. Origin, evolution, and population genetics of the selfish\textitSegregation Distortergene duplication in European and African populations of\textitDrosophila melanogaster: EVOLUTION OF THE SELFISH\textitSDCOMPLEX

   Cara L. Brand, Amanda M. Larracuente, and Daven C. Presgraves

   Evolution, May 2015

   Publisher: Wiley

   DOI
3. Sex-Ratio Meiotic Drive and Y-Linked Resistance in \textitDrosophila affinis

   Robert L Unckless, Amanda M Larracuente, and Andrew G Clark

   Genetics, Mar 2015

   Publisher: Oxford University Press (OUP)

   Abs DOI

   Abstract Genetic elements that cheat Mendelian segregation by biasing transmission in their favor gain a significant fitness benefit. Several examples of sex-ratio meiotic drive, where one sex chromosome biases its own transmission at the cost of the opposite sex chromosome, exist in animals and plants. While the distorting sex chromosome gains a significant advantage by biasing sex ratio, the autosomes, and especially the opposite sex chromosome, experience strong selection to resist this transmission bias. In most well-studied sex-ratio meiotic drive systems, autosomal and/or Y-linked resistance has been identified. We specifically surveyed for Y-linked resistance to sex-ratio meiotic drive in Drosophila affinis by scoring the sex ratio of offspring sired by males with a driving X and one of several Y chromosomes. Two distinct types of resistance were identified: a restoration to 50/50 sex ratios and a complete reversal of sex ratio to all sons. We confirmed that fathers siring all sons lacked a Y chromosome, consistent with previously published work. Considerable variation in Y-chromosome morphology exists in D. affinis, but we showed that morphology does not appear to be associated with resistance to sex-ratio meiotic drive. We then used two X chromosomes (driving and standard) and three Y chromosomes (susceptible, resistant, and lacking) to examine fertility effects of all possible combinations. We find that both the driving X and resistant and lacking Y have significant fertility defects manifested in microscopic examination of testes and a 48-hr sperm depletion assay. Maintenance of variation in this sex-ratio meiotic drive system, including both the X-linked distorter and the Y-resistant effects, appear to be mediated by a complex interaction between fertility fitness and transmission dynamics.

4. Simple Method for Fluorescence DNA \textlessem\textgreaterIn Situ\textless/em\textgreater Hybridization to Squashed Chromosomes

   Amanda M. Larracuente and Patrick M. Ferree

   Journal of Visualized Experiments, Jan 2015

   Publisher: MyJove Corporation

   DOI

2014

1. The organization and evolution of the Responder satellite in species of the Drosophila melanogaster group: dynamic evolution of a target of meiotic drive

   Amanda M Larracuente

   BMC Evolutionary Biology, Dec 2014

   Publisher: Springer Science and Business Media LLC

   DOI
2. Recent Selection on the Y-to-Dot Translocation in Drosophila pseudoobscura

   Amanda M. Larracuente and Andrew G. Clark

   Molecular Biology and Evolution, Apr 2014

   Publisher: Oxford University Press (OUP)

   DOI

2013

1. Surprising Differences in the Variability of Y Chromosomes in African and Cosmopolitan Populations of\textitDrosophila melanogaster

   Amanda M Larracuente and Andrew G Clark

   Genetics, Jan 2013

   Publisher: Oxford University Press (OUP)

   Abs DOI

   AbstractThe nonrecombining Drosophila melanogaster Y chromosome is heterochromatic and has few genes. Despite these limitations, there remains ample opportunity for natural selection to act on the genes that are vital for male fertility and on Y factors that modulate gene expression elsewhere in the genome. Y chromosomes of many organisms have low levels of nucleotide variability, but a formal survey of D. melanogaster Y chromosome variation had yet to be performed. Here we surveyed Y-linked variation in six populations of D. melanogaster spread across the globe. We find surprisingly low levels of variability in African relative to Cosmopolitan (i.e., non-African) populations. While the low levels of Cosmopolitan Y chromosome polymorphism can be explained by the demographic histories of these populations, the staggeringly low polymorphism of African Y chromosomes cannot be explained by demographic history. An explanation that is entirely consistent with the data is that the Y chromosomes of Zimbabwe and Uganda populations have experienced recent selective sweeps. Interestingly, the Zimbabwe and Uganda Y chromosomes differ: in Zimbabwe, a European Y chromosome appears to have swept through the population.

2012

1. The Selfish\textitSegregation DistorterGene Complex of\textitDrosophila melanogaster

   Amanda M Larracuente and Daven C Presgraves

   Genetics, Sep 2012

   Publisher: Oxford University Press (OUP)

   Abs DOI

   AbstractSegregation Distorter (SD) is an autosomal meiotic drive gene complex found worldwide in natural populations of Drosophila melanogaster. During spermatogenesis, SD induces dysfunction of SD+ spermatids so that SD/SD+ males sire almost exclusively SD-bearing progeny rather than the expected 1:1 Mendelian ratio. SD is thus evolutionarily “selfish,” enhancing its own transmission at the expense of its bearers. Here we review the molecular and evolutionary genetics of SD. Genetic analyses show that the SD is a multilocus gene complex involving two key loci—the driver, Segregation distorter (Sd), and the target of drive, Responder (Rsp)—and at least three upward modifiers of distortion. Molecular analyses show that Sd encodes a truncated duplication of the gene RanGAP, whereas Rsp is a large pericentromeric block of satellite DNA. The Sd–RanGAP protein is enzymatically wild type but mislocalized within cells and, for reasons that remain unclear, appears to disrupt the histone-to-protamine transition in drive-sensitive spermatids bearing many Rsp satellite repeats but not drive-insensitive spermatids bearing few or no Rsp satellite repeats. Evolutionary analyses show that the Sd–RanGAP duplication arose recently within the D. melanogaster lineage, exploiting the preexisting and considerably older Rsp satellite locus. Once established, the SD haplotype collected enhancers of distortion and suppressors of recombination. Further dissection of the molecular genetic and cellular basis of SD-mediated distortion seems likely to provide insights into several important areas currently understudied, including the genetic control of spermatogenesis, the maintenance and evolution of satellite DNAs, the possible roles of small interfering RNAs in the germline, and the molecular population genetics of the interaction of genetic linkage and natural selection.

2010

1. Translocation of Y-Linked Genes to the Dot Chromosome in Drosophila pseudoobscura

   Amanda M. Larracuente, Mohamed A. F. Noor, and Andrew G. Clark

   Molecular Biology and Evolution, Jul 2010

   Publisher: Oxford University Press (OUP)

   DOI

2009

1. Comparative Genomics on the \textitDrosophila Phylogenetic Tree

   Nadia D. Singh, Amanda M. Larracuente, Timothy B. Sackton, and 1 more author

   Annual Review of Ecology, Evolution, and Systematics, Dec 2009

   Publisher: Annual Reviews

   Abs DOI

   With the sequencing of 12 complete euchromatic Drosophila genomes, the genus Drosophila is a leading model for comparative genomics. In this review, we discuss the novel insights into evolutionary processes afforded by the newly available genomic sequences when placed in the context of the phylogeny. We focus on three levels: insights into whole-genome content, such as changes in genome size and content across the phylogeny; insights into large-scale patterns of divergence and conservation, such as selective constraints on genes and chromosome-level evolution of sex chromosomes; and insights into finer-scale processes in individual lineages and genes, such as lineage-specific evolution in response to ecological context. As the field of comparative genomics is still young, we also discuss current challenges, such as the development of more sophisticated evolutionary models to capture nonequilibrium processes and the improvement of assembly and alignment algorithms to better capture uncertainty in the data.

2008

1. Evolution of protein-coding genes in Drosophila

   Amanda M. Larracuente, Timothy B. Sackton, Anthony J. Greenberg, and 6 more authors

   Trends in Genetics, Mar 2008

   Publisher: Elsevier BV

   DOI
2. Contrasting the Efficacy of Selection on the X and Autosomes in Drosophila

   N. D. Singh, A. M. Larracuente, and A. G. Clark

   Molecular Biology and Evolution, Jan 2008

   Publisher: Oxford University Press (OUP)

   DOI

2007

1. Evolution of genes and genomes on the Drosophila phylogeny

   Drosophila 12 Genomes Consortium

   Nature, Nov 2007

   Publisher: Springer Science and Business Media LLC

   DOI