Search bioRxiv⌕ Search

SEARCH · Search bioRxiv

Results for “Genetics”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
bioRxiv2022

A Theory for High-Throughput Genetic Interaction Screening

Systematic, genome-scale genetic screens have been instrumental for elucidating genotype-phenotype relationships, but approaches for probing genetic interactions have been limited to at most [~]100 pre-selected gene combinations in mammalian cells. Here, we introduce a theory for high-throughput genetic interaction screens. The theory extends our recently developed Multiplexing using Spectral Imaging and Combinatorics (MuSIC) approach to propose [~]105 spectrally unique, genetically-encoded MuSIC barcodes from 18 currently available fluorescent proteins. Simulation studies based on constraints imposed by spectral flow cytometry equipment suggest that genetic interaction screens at the human genome-scale may be possible if MuSIC barcodes can be paired to guide RNAs. While experimental testing of this theory awaits, it offers transformative potential for genetic perturbation technology and knowledge of genetic function. More broadly, the availability of a genome-scale spectral barcode library for non-destructive identification of single-cells could find more widespread applications such as traditional genetic screening and high-dimensional lineage tracing.

biochemistry↗
bioRxiv2022

Hybrid Breakdown in Male Reproduction Between Recently-Diverged Drosophila melanogaster Populations Has a Complex and Variable Genetic Architecture

Populations no longer experiencing a sufficient rate of gene flow will accumulate genetic differences over time. One potential consequence of divergence between natural populations is hybrid breakdown, which can occur during secondary contact when untested allelic combinations in hybrids beyond the F1 generation are maladaptive and restrict gene flow. Hybrid breakdown is an important process in the development and maintenance of species boundaries, and has largely been studied between populations that are completely or nearly completely isolated. Here, we leverage the recent worldwide expansion of Drosophila melanogaster to investigate signatures of hybrid breakdown between populations that diverged within approximately the last 13,000 years. We did not find clear evidence for hybrid breakdown in viability or female reproductive performance. In contrast, we found that many but not all between-population crosses yielded an elevated fraction of second generation male offspring that were unable to reproduce. The frequency of non-reproducing F2 males varied among different crosses involving the same southern African and European populations, as did the qualitative effect of cross direction, implying a genetically variable basis of hybrid breakdown and a role for uniparentally inherited factors. The levels of male reproductive failure observed in F2 hybrids were not recapitulated in backcrossed individuals, suggesting the existence of incompatibilities with at least three partners. These results suggest that some of the very first steps toward reproductive isolation may involve incompatibilities with complex and variable genetic architectures, and they support the prediction that hybrid breakdown affects the heterogametic sex first. Collectively, our findings on polymorphic incompatibilities within D. melanogaster emphasize this systems potential for future studies on the genetic and organismal basis of early-stage reproductive isolation. IMPACT SUMMARYThe biological diversity that exists around the world is an emergent property of the generation of forms, which are commonly grouped into units we call species. The rate at which new species form can be influenced by the evolution of reproductive isolation, the inability of groups to interbreed. When reproductive isolation is studied in its nascent stages, researchers can gain critical insights into the genetic architectures and evolutionary forces underlying the earliest steps toward speciation. One process that may contribute to early-stage reproductive isolation is hybrid breakdown, when genetic incompatibilities in the offspring of hybrid individuals reduce their fitness. Here, we illuminate a complex pattern of hybrid breakdown among natural populations of Drosophila flies that diverged within the past 13,000 years. We find signals of hybrid breakdown involving male reproduction, between some but not all population pairs, whereas we find no clear evidence for hybrid breakdown impacting female reproduction or developmental survival. These findings are in agreement with Haldanes Rule, which posits that hybrid incompatibilities are more likely to affect the sex that carries distinct sex chromosomes (here, XY males). From certain crosses between African and European fly strains, we find strongly elevated rates of reproductive failure in second generation hybrid males, but outcomes vary dramatically depending on the individual strains crossed. We also provide evidence of incompatibilities underlying male reproductive failure that involve three or more genes, including uniparental factors such as the Y chromosome or mitochondrial genome. Our results highlight a complex and variable basis of hybrid breakdown during the earliest stages of reproductive isolation, in contrast to commonly envisioned scenarios that focus on two-locus incompatibilities caused by fixed genetic differences between groups. These findings also suggest that recently diverged populations of D. melanogaster provide notable opportunities for future studies of the genetic basis of early-stage reproductive isolation.

evolutionary biology↗
bioRxiv2022

Strong selection is poorly aligned with genetic variation in Ipomoea hederacea: implications for divergence and constraint

The multivariate evolution of populations is the result of the interactions between natural selection, drift, and the underlying genetic structure of the traits involved. Covariances among traits bias responses to selection, and the multivariate axis which describes the greatest genetic variation is expected to be aligned with patterns of divergence across populations. An exception to this expectation is when selection acts on trait combinations lacking genetic variance, which limits evolutionary change. Here we used a common garden field experiment of individuals from 57 populations of Ipomoea hederacea to characterize linear and nonlinear selection on five quantitative traits in the field. We then formally compare patterns of selection to previous estimates of within population genetic covariance structure (the G-matrix) and population divergence in these traits. We found that selection is poorly aligned with previous estimates of genetic covariance structure and population divergence. In addition, the trait combinations favoured by selection were generally lacking genetic variation, possessing approximately 15- 30% as much genetic variation as the most variable combination of traits. Our results suggest that patterns of population divergence are likely the result of the interplay between adaptive responses, correlated response, and selection favoring traits lacking genetic variation.

evolutionary biology↗
bioRxiv2022

Standing genetic variation and chromosome differences drove rapid ecotype formation in a major malaria vector

Species distributed across heterogeneous environments often evolve locally adapted ecotypes, but understanding of the genetic mechanisms involved in their formation and maintenance in the face of gene flow is incomplete. In Burkina Faso, the major African malaria mosquito Anopheles funestus comprises two strictly sympatric and morphologically indistinguishable yet karyotypically differentiated forms reported to differ in ecology and behavior. However, knowledge of the genetic basis and environmental determinants of An. funestus diversification was impeded by lack of modern genomic resources. Here, we applied deep whole-genome sequencing and analysis to test the hypothesis that these two forms are ecotypes differentially adapted to breeding in natural swamps versus irrigated rice fields. We demonstrate genome-wide differentiation despite extensive microsympatry, synchronicity, and ongoing hybridization. Demographic inference supports a split only ~1,300 years ago, closely following the massive expansion of domesticated African rice cultivation ~1,850 years ago. Regions of highest divergence, concentrated in chromosomal inversions, were under selection during lineage splitting, consistent with local adaptation. The origin of nearly all variation implicated in adaptation, including chromosomal inversions, substantially predates the ecotype split, suggesting that rapid adaptation was fueled mainly by standing genetic variation. Sharp inversion frequency differences likely facilitated adaptive divergence between ecotypes, both by suppressing recombination between opposing chromosomal orientations of the two ecotypes, and by maximizing recombination within the structurally monomorphic rice ecotype. Our results align with growing evidence from diverse taxa that rapid ecological diversification can arise from evolutionarily old structural genetic variants that modify genetic recombination. Significance StatementLocal adaptation to heterogeneous environments is pervasive, but its underlying genetic basis is incompletely understood. Within a major African malaria vector, An. funestus, are two chromosomally differentiated groups that are co-localized, morphologically indistinguishable, and reported to differ both in ecology and behavior relevant to malaria transmission and control. Progress in understanding the genetic basis and environmental determinants of vector diversification was impeded by the lack of modern genomic resources. Here we perform deep whole-genome sequencing on individuals from these groups, establishing that they are differentiated genome-wide in a manner consistent with recent ecotype formation associated with the exploitation of a new anthropogenic larval habitat. Such rapid malaria vector diversification was facilitated by standing genetic variation, including evolutionarily old chromosomal rearrangements.

evolutionary biology↗
bioRxiv2023

A prebiotic genetic alphabet as an early Darwinian ancestor for pre-RNA evolution

RNA-based genetic code is thought to be central to lifes emergence due to its dual ability for information transfer and catalysis. Nonetheless, the genetic code of early life was potentially not restricted to canonical genetic alphabets alone. The presence of an extensive repertoire of modified nucleobases in extant biology as signatures of the past, highlights the relevance of non-canonical alphabets, ably strengthened by experiments demonstrating their ready conversion into nucleosides and nucleotides. All these strongly support a pre-RNA World, wherein informational molecules are posited to have contained alternate genetic alphabets. Nevertheless, understanding pre-RNA molecules capacity to acquire emergent function has remained less prevalent. Further, the steps involved in their transition to a canonical RNA World has not been systematically studied in the origins of life framework. In this study, we report the synthesis of a prebiotically relevant genetic alphabet containing the non-canonical nucleobase, barbituric acid. We demonstrate for the first instance the enzymatic incorporation of this prebiotically plausible alphabet (BaTP) into an RNA, using proteinaceous T7 RNA polymerase. Pertinently, the incorporation of this genetic alphabet into a baby spinach aptamer did not affect its overall secondary structure, while also allowing it to retain its aptameric function. Furthermore, we demonstrate the faithful transfer of genetic information from pre-RNA-containing barbitudine nucleotides to DNA, using a high-fidelity RNA-dependent DNA polymerase. These findings allude to a putative pathway for the early molecular evolution of the genetic code of extant life.

biochemistry↗
bioRxiv2023

Genetic variation in Loudetia simplex supports the presence of ancient grasslands in Madagascar

O_LIResearch Aims -- The extent of Madagascars grasslands prior to human colonization is unresolved. We used population genetic analyses of a broadly dominant C4 fire-adapted grass, Loudetia simplex, as a proxy for estimating grassland change through time. We carefully examined the utility of target-enrichment data for population genetics to make recommendations for conservation genetics. We explored the potential of estimating individual ploidy levels from target-enrichment data and how assumptions about ploidy could affect analyses. C_LIO_LIMethods -- We developed a novel bioinformatic pipeline to estimate ploidy and genotypes from target-enrichment data. We estimated standard population genetic summary statistics in addition to species trees and population structure. Extended Bayesian skyline plots provided estimates of population size through time for empirical and simulated data. C_LIO_LIKey Result -- All Malagasy Loudetia simplex individuals sampled in this study formed a clade and possibly indicated an ancestral Central Highland distribution of 800m in altitude and above. Demographic models suggested grassland expansions occurred prior to the Last Interglacial Period and supported extensive grasslands prior to human colonization. Though there are limitations to target-enrichment data for population genetic studies, we find that analyses of population structure are reliable. C_LIO_LIKey Point --Genetic variation in Loudetia simplex supports widespread grasslands in Madagascar prior to the more recent periods of notable paleoclimatic change. However, the methods explored here could not differentiate between paleoclimatic change near the Last Glacial Maximum and anthropogenic effects. Target-enrichment data can be a valuable tool for analyses of population structure in the absence a reference genome. C_LI Societal Impact StatementRecognizing Loudetia dominated grasslands were widespread prior to human colonization highlights that open ecosystems were and continue to be an important component of Madagascars biodiversity. Urgently required are biodiversity inventories and integrative taxonomic treatments of grassland flora and fauna to asses risks to understudied ecosystems historically regarded as wastelands. Substantial financial and logistical barriers exist to implementing conservation studies using contemporary genomic tools. We ameliorated some of the challenges for population genetic analyses of non-model polyploids lacking reference genomes by developing computational resources to leverage a cost-effective data generation strategy that requires no prior genetic knowledge of the target species. ResumeO_LILes objectifs de la recherche -- Letendue des ecosystemes ouverts de Madagascar avant la colonisation humaine reste a eclaircir. Nous avons utilise une analyse de la population genetique dune graminee C4 adaptee au feu, largement dominante, Loudetia simplex, comme reference pour estimer les changements au niveau de ces biomes au fil du temps. Nous avons examine attentivement lutilite des donnees denrichissement cible pour la genetique de population afin de formuler des recommandations pour la conservation genetique. Nous avons explore le potentiel de lestimation du niveau des ploidies individuelles a partir des donnees denrichissement cible et comment les hypotheses a propos de ces ploidies pourraient affecter les analyses. C_LIO_LILes methodes -- Nous avons developpe un nouveau canal bioinformatique pour estimer les ploidies et les genotypes a partir des donnees denrichissement cible. Nous avons estime les statistiques standard de la population genetique, en plus des arbres des especes et de la structure de la population. Lutilisation des traces etendus du ciel bayesien a fourni une estimation de la taille de la population au fil du temps pour des donnees empiriques et simulees. C_LIO_LIResultat cle -- Tous les individus Malagasy de Loudetia simplex echantillonnes dans cette etude ont forme un clade, indiquant une eventuelle ancienne distribution dans les hauts plateaux. Les modeles demographiques suggerent une expansion des prairies bien avant la derniere periode interglaciaire et soutiennent lexistence dune vaste distribution avant la colonisation humaine. Bien quil y ait des limites a lenrichissement des donnees cibles pour letude de la genetique des populations, nous constatons que lanalyse des structures des populations est fiable. C_LIO_LILes points cles -- La variation genetique de Loudetia simplex soutient lexistence de vastes prairies a Madagascar avant les periodes plus recentes de changements paleoclimatiques notables. Cependant, les methodes explorees ici nont pas permis de faire la difference entre les changements paleoclimatiques pres du dernier maximum glaciaire et les effets anthropogenes. Les donnees denrichissement cible peuvent etre un outil precieux pour les analyses de la structure des populations en labsence dun genome de reference. C_LI Declaration dimpact societalReconnaitre que les prairies dominees par Loudetia etaient repandues avant la colonisation humaine souligne que les ecosystemes ouverts etaient et continuent detre un composant important de la biodiversite de Madagascar. Il est urgent de realiser des inventaires de la biodiversite et une taxonomie integree pour le traitement de la flore et de la faune des ecosystemes ouverts afin devaluer les risques pour les ecosystemes sous-etudies consideres historiquement comme des terres en friches. Des barrieres financieres et logistiques existent pour mettre en uvre letude de la conservation en utilisant les outils genomiques contemporains. Nous avons ameliore certains des defis lies aux analyses genetiques de populations de polyploides non modeles, sans genomes de reference, en developpant des ressources informatiques pour exploiter une strategie pouvant generer des donnees rentables ne necessitant aucune connaissance genetique prealable de lespece cible. FamintinanaO_LINy tanjonny fikarohana -- Mbola tsy fantatra mazava tsara ny fivelaranny hivoka teto Madagasikara talohanny fahatongavany olombelona. Mba ahafantarana ny fihovana nitranga nandritra ny fotoana naharitra teo aminireo hivoka ireo dia nanao famakafakahana ara-genetika aminny ahitra C4 miompana aminny afo iray antsoina Loudetia simplex ara-tsiantifika na Berambo na Hara aminny teny malagasy izahay. Nandinika tsara ny maha-zava-dehibe ny fampitomboana ny antotan-kevitra mba ahafahana manolo-kevitra momba ny fiarovana ny fototarazo genetika. Nandinika ny mety mampiavaka ny fanombanana anny ploidy tsirairay aminny fampitomboana antotan-kevitra sy ny mety ho fiantraikanny fiheverana momba ireo ploidy ireo aminny fikarohana. C_LIO_LIFomba Fiasa -- Namorona fantsona bioinformatika vaovao mba ahafahana manombana ny ploidy sy ny << genotypes >> avy aminny antotan-kevitra nokendrena izahay. Notombanana ny antontanisa famintinana ny fototarazo ara-genetikanireo vondronahitra ireo, miampy ny karazana hazo sy ny firafitry ny vondrona na koa hoe mponina. Nanome tombantombana ny habenny mponina aminny alalanny fotoana ny antontan-kevitra voavinavina azo taminny fikarohana. Fikarohana izay azo taminny alalanny << Bayesina Skuline Plots >>. C_LIO_LIVokam-pikarohana fototra -- Ny vondrona Loudetia simplex eto Madagasikara izay niasana dia namorona << clade >> na fikambanana iray, izay manondro ny mety maha ela netezana sy tranainy anio ahitra io eny aminny faritra avo. Ny modely demografika dia manoro hevitra aminny naha be velarana ny hivoka izay efa ela talohanny vanim-potoana << interglacial >> farany ary manohana ny fivelarana midadasika anireo kijana ireo alohanny fonenanny olombelona. Na dia misy fetrany aza ny fampitomboana ny antotan-kevitra kendrena aminny fandalinana ny fototarazo genetika mombanny mponina, dia hita fa azo itokisana ny fikarohana natao mombanny firafitry ny mponina. C_LIO_LIHevi-dehibe -- Ny fahasamihafana ara-genetika ao aminny Loudetia simplex dia manohana ny fisianny hivoka na kijana midadasika eto Madagasikara talohanny vanim-potoananny fiovana paleoclimatika nisongadina. Na izany aza, ny fombam-pikarohana nampiasana teto dia tsy nahavita nanavaka ny fiovanny paleoclimatika akaikinny vanim-potoana lehibe nangatsiaka farany sy ny vokatry ny fitrandrahana nataonny olombelona. Mety ho fitaovana manan-danja aminny famakafakana ny firafitry ny mponina ny antotan-kevitra nampitombona na dia tsy misy fitaovana genomika iangaina aza. C_LI Fanambarana fiantraika ara-tsosialyNy fanekena fa niely patrana ny hivoka itoeranny Loudetia talohanny fanjanahanny olombelona dia manamarika fa ireo hivoka ireo dia singa manan-danja aminny zavamananaina eto Madagasikara. Ilaina maika ny fahafantarana ara biolojika sy taxononomique ny zavamaniry sy ny biby aminny hivoka mba hanombanana ny loza mety hitranga aminny hivoka izay tsy ananana fahalalana maro sady heverina ho tany maina. Misy sakana ara-bola sy ara-pitaovana aminny fampiharana ny fandalinana momba ny fiarovana izay nampiasana fitaovana genomika ankehitriny. Nohatsarainay ny sasany aminireo fanamby mifandraika aminny famakafakana ara-genetika ny mponina manana ploidy maro tsy modely, izay tsy misy fitaovana genomika iaingana, aminny alalanny fampivoarana loharanon-kevitra kajy mba hitrandrahana paikady izay mety hiteraka angon-drakitra mahomby tsy mitaky fahalalana mahakasika ny fototarazo ara-genetika ny zava-maniry izay tiana karohina.

evolutionary biology↗
bioRxiv2023

Considerable genetic diversity and structure despite endemism and limited ecological specialization in the Hayden's ringlet, Coenonympha haydenii

Understanding the processes that underlie the development of population genetic structure is central to the study of evolution. Patterns of genetic structure, in turn, can reveal signatures of local adaptation, barriers to gene flow, or even the genesis of speciation. However, it is unclear whether the processes that dominate the development of genetic structure differ in populations with a severely restricted range relative to widespread species. For example, in narrowly endemic species, is population structure likely to be adaptive in nature (e.g., via niche specialization), or rather the result of genetic drift (e.g., isolation by distance)? In this study, we investigated patterns of genetic diversity and structure in the narrow endemic Haydens ringlet butterfly. Specifically, we asked to what degree genetic structure in the Haydens ringlet can be explained by isolation by distance, barriers to gene flow, and host association. We employed a genotyping-by-sequencing (GBS) approach coupled with host preference assays, Bayesian modeling, and population genomic analyses to answer these questions. Our results suggest that despite their restricted range, levels of genetic diversity in the Haydens ringlet are comparable to those seen in non-endemic butterfly species. Haydens ringlets showed a strong preference for feeding on grasses vs. sedges, but neither host preference nor potential host availability at sampling sites correlated with genetic structure. We conclude that geography, in the form of barriers to migration and simple isolation by distance, were the major drivers of differentiation in this endemic species.

evolutionary biology↗
bioRxiv2023

Influenza A genomic diversity during human infections underscores the strength of genetic drift and the existence of tight transmission bottlenecks

Influenza infections result in considerable public health and economic impacts each year. One of the contributing factors to the high annual incidence of human influenza is the viruss ability to evade acquired immunity through continual antigenic evolution. Understanding the evolutionary forces that act within and between hosts is therefore critical to interpreting past trends in influenza virus evolution and in predicting future ones. Several studies have analyzed the longitudinal patterns of influenza A virus genetic diversity in natural human infections to assess the relative contributions of selection and genetic drift on within-host evolution. However, in these natural infections, within-host viral populations harbor very few single nucleotide variants, limiting our resolution in understanding the forces acting on these populations in vivo. Further, low levels of within host viral genetic diversity limit the ability to infer the extent of drift across transmission events. Here, we propose to use influenza virus genomic diversity as an alternative signal to better understand within and between host patterns of viral evolution. Specifically, we focus on the dynamics of defective viral genomes (DVGs) which harbor large internal deletions in one or more of influenza viruss eight gene segments. Our longitudinal analyses of DVGs show that influenza A virus populations are highly dynamic within hosts, corroborating previous findings based on viral genetic diversity that point towards the importance of genetic drift in driving within-host viral evolution. Further, our analysis of DVG populations across transmission pairs indicate that DVGs rarely appeared to be shared, consistent with previous findings indicating the presence of tight transmission bottlenecks. Our analyses demonstrate that viral genomic diversity can be used to complement analyses based on viral genetic diversity to reveal processes that drive viral evolution within and between hosts. Author summaryDuring viral replication within infected individuals, different types of mutation can occur. Point mutations introduce genetic diversity, with some sites in the viral genome becoming polymorphic at the viral population level. Structural mutations that result in deletions in the viral genome can also occur, contributing to genomic diversity in the viral population. Defective viral genomes (DVGs) are a particular type of this genomic diversity that are incapable of establishing productive infection on their own, but persist during infection through cellular coinfection with infectious virus. Here, we first identify DVGs in deep sequencing data from natural infections of influenza A virus subtype H3N2 and then use these DVGs to inform our understanding of within-host viral evolution and transmission dynamics. By analyzing DVG populations over time within infected individuals and between transmission pairs, we find that influenza A virus populations are shaped by genetic drift and tight transmission bottlenecks. Our results add to our understanding of influenza genomic diversity within-and between-hosts and demonstrate the possibility of considering the full suite of viral diversity to understand drivers of viral evolution.

evolutionary biology↗
bioRxiv2023

A robust association test leveraging unknown genetic interactions: Application to cystic brosis lung disease

For complex traits such as lung disease in Cystic Fibrosis (CF), Gene x Gene or Gene x Environment interactions can impact disease severity but these remain largely unknown. Unaccounted-for genetic interactions introduce a distributional shift in the quantitative trait across the genotypic groups. Joint location and scale tests, or full distributional differences across genotype groups can account for unknown genetic interactions and increase power for gene identification compared with the conventional association test. Here we propose a new joint location and scale test (JLS), a quantile regression-basd JLS (qJLS), that addresses previous limitations. Specifically, qJLS is free of distributional assumptions, thus applies to non-Gaussian traits; is as powerful as the existing JLS tests under Gaussian traits; and is computationally efficient for genome-wide association studies (GWAS). Our simulation studies, which model unknown genetic interactions, demonstrate that qJLS is robust to skewed and heavy-tailed error distributions and is as powerful as other JLS tests in the literature under normality. Without any unknown genetic interaction, qJLS shows a large increase in power with non-Gaussian traits over conventional association tests and is slightly less powerful under normality. We apply the qJLS method to the Canadian CF Gene Modifier Study (n=1,997) and identified a genome-wide significant variant, rs9513900 on chromosome 13, that had not previously been reported to contribute to CF lung disease. qJLS provides a powerful alternative to conventional genetic association tests, where interactions my contribute to a quantitative trait. Author summaryCystic fibrosis (CF) is a genetic disorder caused by loss-of-function variants in CF transmembrane conductance regulator (CFTR) gene, leading to disease in several organs and notably the lungs. Even among those who share identical CF causing variants, their lung disease severity is variable, which is presumed to be caused in part by other genes besides CFTR referred to as modifier genes. Several genome-wide association studies of CF lung disease have identified associated loci but these account for only a small fraction of the total CF lung disease heritability. This may be due to other environmental factors such as infections, smoke exposure, socioeconomic status, treatment of lung diseases or a numerous other unknown or unmeasured factors that may interact with modifier genes. A class of new statistical methods can leverage these unknown interactions to better detect putative genetic loci. We provide a comprehensive simulation study that incorporates unknown interactions and we show that these statistical methods perform better than conventional approaches at identifying contributing genetic loci when the assumptions for these approaches are met. We then develop an approach that is robust to the typical normal assumptions, provide software for implementation and we apply it to the Canadian CF Gene Modifier Study to identify novel variants contributing to CF lung disease.

genomics↗
bioRxiv2023

Sperm traits of the three genetic morphs in the ruff sandpiper

BackgroundThe ruff sandpiper Calidris pugnax is a Palearctic lekking shorebird with three genetic morphs determined by an autosomal inversion. Male morphs differ strikingly in body size, ornaments, endocrinology and mating behavior. Aggressive Independents represent the ancestral haplotype, while female-mimicking Faeders and semi-cooperative Satellites are the inverted haplotypes. Because one inversion breakpoint is homozygous lethal, the inverted haplotypes cannot recombine and are expected to accumulate deleterious mutations. The inversion regions also harbor genes involved in spermatogenesis. However, it remains unknown whether the genetic differences between the morphs also translate into differences in sperm traits. Here, we use a captive-bred population of ruffs to compare sperm swimming speed and morphology among the morphs. ResultsRuff sperm morphologically resembled those of passerines, but moved differently, vibrating from side to side while slowly moving forward, rather than rotating while moving forward. Faeder sperm moved the slowest, which is consistent with the prediction of genetic deterioration over time. However, against expectation, sperm of Independents did not seem to be of the highest quality, i.e., their sperm were not the fastest nor the least variable, and they had sperm with the shortest tail and midpiece. Although the midpiece contains the energy-producing mitochondria, sperm midpiece length was not associated with sperm swimming speed. Instead, two of three velocity metrics weakly positively correlated with head length (absolute and relative). ConclusionsThe three genetically determined ruff morphs showed subtle differences in swimming speed and in the length of some sperm components. However, the between-morph differences in sperm swimming speed were not linked to the differences in morphology. We conclude that there is at best limited evidence for lower-quality sperm in the morphs that carry the inversion, and suggest that the potential for the evolution of morph-specific sperm adaptations may be limited in this system. Lay SummaryThe ruff sandpiper is a shorebird that exhibits three genetically distinct types of males, which differ markedly in body size, ornaments, hormones, and mating behavior. Aggressive Independents represent the type that evolved first. Semi-cooperative Satellites and female-mimicking Faeders evolved later through a specific type of genetic rearrangement called an inversion, in which a segment of a chromosome reversed in orientation. Due to the nature of this inversion, Satellite and Faeder chromosomes are expected to deteriorate over time. However, it remains unclear whether the genetic differences between these morphs, which affect physiological and behavioral traits, also translate into differences in sperm traits. We used a captive population of ruffs to compare sperm swimming speed and length measurements between the three types of males. Faeder sperm was the slowest, which is consistent with expectations based on genetic deterioration over time. However, against our expectations, the sperm of Independents does not appear to have better performance characteristics. Although the midpiece of a sperm is responsible for energy production, the length of the midpiece did not relate to sperm swimming speed.

evolutionary biology↗
bioRxiv2023

Assessing the links between pollinators and the genetic and epigenetic features of plant species with contrasting distribution ranges

In flowering plants, pollinators contribute to gene flow while they also respond to variation in plant traits together determined by genetic, epigenetic and environmental sources of variation. Consequently, a correlation between abundance and diversity of pollinators and the genetic and epigenetic characteristics of plant populations such as diversity or distinctiveness is to be expected, yet no study has explored such long-term dimensions of plant-pollinator interactions. Mediterranean narrow endemics often exhibit unexpectedly high levels of population (epi)genetic diversity. We hypothesize that pollinators may contribute to explain this pattern. Specifically, we expect a stronger association of pollinators with population (epi)genetic variability in narrow endemics than in widely distributed congeners. We studied five pairs of congeneric plant species, consisting of one narrow endemic with a restricted distribution and one widespread congener, found in the Sierra de Cazorla mountains (SE Spain). In up to three populations per species, a comprehensive characterisation of pollinators was carried out to estimate pollinator diversity and visitation rate. Genetic and epigenetic diversity and distinctiveness of each population was calculated using AFLP markers and methylation-sensitive AFLP markers (MSAP) respectively. The relationships with pollinator diversity and visitation rate were assessed. The diversity of pollinators did not vary according to the plant distribution range, whereas visitation rate was higher in widespread species. As predicted, only narrow endemics showed a significant association between pollinators and their population genetic and epigenetic characteristics. Specifically, higher pollinator diversity and visitation rates entailed higher population genetic diversity and lower epigenetic distinctiveness. This work shows the value of exploring the relationships between pollinator abundance and diversity and population (epi)genetics for understanding the evolution of plant rarity.

ecology↗
bioRxiv2023

Serial dilution shapes genetic variation and defines conservation units in Asian elephants

Asian elephants (Elephas maximus) are the largest extant terrestrial megaherbivores native to Asia, with 60% of their wild population found in India. Despite ecological and cultural importance, their population genetic structure and diversity, demographic history, and ensuing implications for management/conservation remain understudied. We analysed 34 whole genomes (between 11X - 32X) from most known elephant landscapes in India and identified five management/conservation units corresponding to elephants in Northern (Northwestern/Northeastern) India, Central India and three in Southern India. Our genetic data reveal signatures of serial colonisation, and a dilution of genetic diversity from north to south of India. The Northern populations diverged from other populations more than 70,000 years ago, have higher genetic diversity, and low inbreeding/high effective size (Pi = 0.0016{+/-}0.0001; FROH> 1MB= 0.09{+/-}0.03). Two of three populations in Southern India (South of Palghat Gap: SPG, and South of Shencottah Gap:SSG) have low diversity and are inbred, with very low effective population sizes compared to current census sizes (Pi = 0.0014{+/-}0.00009 and 0.0015{+/-}0.0001; FROH> 1MB= 0.25{+/-}0.09 and 0.17{+/-}0.02). Analyses of genetic load reveals purging of potentially high-effect insertion/deletion (indel) deleterious alleles in the Southern populations and potential dilution of all deleterious alleles from north to south in India. However, despite dilution and purging for the damaging mutation load in Southern India, the load that remains is homozygous. High homozygosity of deleterious alleles, coupled with low neutral genetic diversity make these populations (SPG and SSG) high priority for conservation attention. Most surprisingly, our study suggests that patterns of genetic diversity and genetic load can correspond to geographic signatures of serial founding events, even in large, highly mobile, endangered mammals.

evolutionary biology↗
bioRxiv2023

A study of genetic variants associated with skin traits in the Vietnamese population

BackgroundMost skin-related traits have been studied from Caucasian genetic background. A comprehensive study on skin-associated genetic effects on under-represented populations like Vietnam is needed to fill the gaps in the field. ObjectivesTo develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole genome sequencing (WGS) data of 1000 genomes project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). By using this information we may have a better understanding of the susceptibility of Vietnamese people. MethodsVietnamese cohorts of whole genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrients requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. ResultsThe skin-related genetic profile of Vietnamese cohorts is similar at most with East Asian (JPT: Fst=0.036, CHB: Fst=0.031, CHS: Fst=0.027, CDX: Fst=0.025) in the population study. In addition, we identified pairs of skin traits being at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p =1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3). ConclusionThis is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.

bioinformatics↗
bioRxiv2023

MGDrivE 3: A decoupled vector-human framework for epidemiological simulation of mosquito genetic control tools and their surveillance

Novel mosquito genetic control tools, such as CRISPR-based gene drives, hold great promise in reducing the global burden of vector-borne diseases. As these technologies advance through the research and development pipeline, there is a growing need for modeling frameworks incorporating increasing levels of entomological and epidemiological detail in order to address questions regarding logistics and biosafety. Epidemiological predictions are becoming increasingly relevant to the development of target product profiles and the design of field trials and interventions, while entomological surveillance is becoming increasingly important to regulation and biosafety. We present MGDrivE 3 (Mosquito Gene Drive Explorer 3), a new version of a previously-developed framework, MGDrivE 2, that investigates the spatial population dynamics of mosquito genetic control systems and their epidemiological implications. The new framework incorporates three major developments: i) a decoupled sampling algorithm allowing the vector portion of the MGDrivE framework to be paired with a more detailed epidemiological framework, ii) a version of the Imperial College London malaria transmission model, which incorporates age structure, various forms of immunity, and human and vector interventions, and iii) a surveillance module that tracks mosquitoes captured by traps throughout the simulation. Example MGDrivE 3 simulations are presented demonstrating the application of the framework to a CRISPR-based homing gene drive linked to dual disease-refractory genes and their potential to interrupt local malaria transmission. Simulations are also presented demonstrating surveillance of such a system by a network of mosquito traps. MGDrivE 3 is freely available as an open-source R package on CRAN (https://cran.r-project.org/package=MGDrivE2) (version 2.1.0), and extensive examples and vignettes are provided. We intend the software to aid in understanding of human health impacts and biosafety of mosquito genetic control tools, and continue to iterate per feedback from the genetic control community. Author summaryVector-borne diseases such as malaria cause massive morbidity and mortality throughout much of the world. Currently-available control measures, such as insecticide-based tools and antimalarial drugs, have limited impact and are waning in effectiveness, hence there is a need for novel tools to complement existing ones. Mosquito genetic control tools, such as gene drive systems and genetic versions of the sterile insect technique, offer a range of promising options, the development of which has greatly expanded since the advent of CRISPR-based gene-editing. Recently, we proposed MGDrivE 2 (Mosquito Gene Drive Explorer 2), which incorporates epidemiology into simulations of the dynamics of these systems in spatially-structured mosquito populations; however, that framework relied on simple model representations of vector-borne diseases. Here, we present MGDrivE 3, which decouples the vector portion of the model from the human portion, allowing the mosquito genetic control framework to be paired with more-detailed epidemiological frameworks. As an example, we implement the human transmission dynamics of the Imperial College London malaria model. We also incorporate a network of mosquito traps for surveillance. As genetic control technology edges closer towards field implementation, more detailed predictions of its epidemiological and biosafety implications are needed. We propose MGDrivE 3 to fulfill this role.

ecology↗
bioRxiv2023

Genetic variation exists within Zea mays to influence unsustainable nitrogen cycling microbiome function

Overuse of synthetic nitrogen fertilizers in agroecosystems causes environmental pollution and human harm at a global level. Nitrogenous fertilizers provide a short-lived benefit to crops in the agroecosystem, but stimulate microbially-mediated nitrification and denitrification, processes that result in N pollution, greenhouse gas (GHG) production, and reduced soil fertility. Recent advances in plant microbiome science suggest that plants can modulate the composition and activity of rhizosphere microbial communities. These rhizosphere communities act as an extended phenotype, primed by genetic variation in the plant host. Genetic variation in traits (e.g., plant secondary metabolites, root architecture, immune system, etc.) act as mechanistic selective agents on the composition of the microbiome. Here we attempted to determine whether genetic variation exists in Zea mays for the ability to influence the extended phenotype of rhizosphere soil microbiome composition and function. Specifically, we determined whether plants influence on soil nitrogen cycling activities was altered by plant genetics and thereby allowing it to be incorporated into breeding practices. To capture an extensive amount of genetic diversity within maize we sampled the rhizosphere microbiome of a germplasm chronosequence that included ex-PVP inbreds, hybrids, and teosinte (Z. mays ssp. mexicana and Z. mays ssp. parviglumis). We observed that potential N cycling processes were influenced by plant genetics. Teosinte and some hybrid genotypes supported microbial communities with lower potential nitrification and potential denitrification activity in the rhizosphere, while inbreds stimulated/did not inhibit these undesirable N-cycling activities. These potential differences translated to functional differences in N2O production, with teosinte plots producing less GHG than maize plots. Furthermore, within these Zea cultivars we found that plant genetics explained a significant amount of variation in the microbiome, particularly among different nitrification and denitrification functional genes within the community. We found that potential nitrification, potential incomplete denitrification, and overall denitrification rates, but not abundance of N-cycling genes of rhizosphere soils were influenced by growth stage and plant genetics. Taken together, these results suggest that crop selection can lead to changes in root phenotypes that could suppress unsustainable N-cycling processes. Reintroducing stress-adapted and "wild" root characteristics into modern germplasm may be a way to manipulate soil microbiomes at both a composition and functional level to improve sustainability.

ecology↗
bioRxiv2023

Migration distance and mating system are not associated with genetic diversity and differentiation among bats (Chiroptera)

Genetic variation is critical for evolutionary responses to environmental change. Links between genetic variation and behavioural or life history traits may reveal how varied strategies influence evolutionary trends in speciation and adaptation. Traits associated with movement typically correlate with population genetic structure and could help predict populations vulnerability to geographic processes such as habitat fragmentation and disease spread. With their wide diversity in behaviours and ecologies, bats provide a useful testing ground for hypotheses about population structure related to species-specific movement patterns. We used a global sample of microsatellite data (n=233 sites from 17 bat species) associated with published studies to examine potential links between genetic variation and migration and mating strategies. The genetic measures we tested were population-specific differentiation, gene diversity, and allelic richness. Using Bayesian models that accounted for phylogenetic distances among species, we identified no correlations between migration or mating strategy and genetic variation. Our results do not support long-standing hypotheses about dispersal-mediated genetic structure, and contrast with prior studies on bat genetic diversity and differentiation. We discuss the need for continued research into the complex association of ecological, biogeographical, and behavioural factors that facilitate gene flow among populations, especially in species with diverse movement patterns.

zoology↗
bioRxiv2023

Precise age estimation in clonal species using a somatic genetic clock

Age and longevity are key parameters for demography and life-history evolution of organisms. In clonal species, a widespread life history among animals, plants, algae and fungi, the sexually produced offspring (the genet) grows indeterminately by producing iterative modules, or ramets. The age of large genets often remains elusive, while estimates based on their spatial extent as proxy for age are unreliable. Here, we present a method for age estimation using a molecular clock based on the accumulation of fixed somatic genetic variation (SoGV) that segregates among ramets of the same genet. Using a stochastic model of a generic clonal organism, we demonstrate that the accumulation of fixed SoGV via somatic genetic drift will approach linearity after a short lag phase, and is determined by the mitotic mutation rate, without direct dependence on asexual generation time. The lag phase decreased with lower stem cell population size (N), number of founder cells for the formation of new modules (N0), and the ratio of symmetric vs. asymmetric stem cell divisions. We apply the somatic genetic clock to the clonal plant model Zostera marina (eelgrass) and show that linearity is approached within a few years. Taking advantage of two long-term cultivation experiments for Z. marina (4 and 17 years respectively) as calibration points, we find genet ages up to 1,403 years in a global data set of 20 eelgrass populations. The somatic genetic clock is applicable to any multicellular clonal species where a small number of founder cells are recruited to form new ramets, opening novel research avenues to study longevity and hence, demography and population dynamics of clonal species.

evolutionary biology↗
bioRxiv2023

Leveraging whole genome sequencing to promote genetic diversity and population health in zoo-housed western lowland gorillas

The sustainability of zoo populations is dependent on maintaining genetic diversity and controlling heritable disease. Here, we explore the integration of whole genome sequencing data in the management of the international zoological population of western lowland gorillas, focusing on genetic diversity and heritable diseases. By comparing kinship values derived from classical pedigree mapping and whole genome sequencing, we demonstrate that genomic data provides a more sensitive measure of relatedness. Our analysis reveals a decrease in genetic diversity due to closed breeding, emphasizing the potential for genetic intervention to mitigate negative impact on population fitness. We identify contributing factors to the decreasing genetic diversity including breeding within a closed population, unknown kinship among potential mates, and disproportionate genetic contributions from individual founders. Additionally, we highlight idiopathic myocardial fibrosis (IMF), a common cardiovascular pathology observed in zoologically housed gorillas, and identify a novel genetic variant in the TNNI3K gene that appears to be associated with this condition. These findings underscore the importance of incorporating molecular data into ex-situ population management strategies, and advocate for the adoption of advanced genomic techniques to optimize the genetic health and diversity of zoologically housed western lowland gorillas.

zoology↗