scholarly journals Female genetic contributions to sperm competition in Drosophila melanogaster

2018 ◽  
Author(s):  
Dawn S. Chen ◽  
Sofie Y.N. Delbare ◽  
Simone L. White ◽  
Jessica L. Sitnik ◽  
Martik Chatterjee ◽  
...  
Keyword(s):  
Nervous System ◽  
Drosophila Melanogaster ◽  
Sperm Competition ◽  
Reproductive Tract ◽  
Seminal Fluid ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Physiological Processes ◽  
Female Genotype ◽  
Mechanistic Basis

In many species, sperm can remain viable in the reproductive tract of a female well beyond the typical interval to remating. This creates an opportunity for sperm from different males to compete for oocyte fertilization inside the female’s reproductive tract. In Drosophila melanogaster, sperm morphology and seminal fluid content affect male success in sperm competition. On the other hand, although genome-wide association studies (GWAS) have demonstrated that female genotype plays a role in sperm competition outcome as well, the biochemical, sensory and physiological processes by which females detect and selectively use sperm from different males remain elusive. Here, we functionally tested 27 candidate genes implicated via a GWAS for their contribution to the female’s role in sperm competition, measured as changes in the relative success of the first male to mate (P1). Of these 27 candidates, we identified eight genes that affect P1 when knocked down in females, and also showed that six of them do so when knocked down in the female nervous system. Two genes in particular, Rim and caup, lowered P1 when knocked down in sensory pickpocket (ppk)+ neurons and octopaminergic Tdc2+ neurons, respectively. These results establish a functional role for the female’s nervous system in the process of sperm competition and expand our understanding of the genetic, neuronal and mechanistic basis of female responses to multiple matings. We propose that through their nervous system, females actively assess male compatibility based on courtship or ejaculates and modulate sperm competition outcome accordingly.

scholarly journals Female Genetic Contributions to Sperm Competition in Drosophila melanogaster

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 789-800 ◽  
Author(s):  
Dawn S. Chen ◽  
Sofie Y. N. Delbare ◽  
Simone L. White ◽  
Jessica Sitnik ◽  
Martik Chatterjee ◽  
...  
Keyword(s):  
Nervous System ◽  
Drosophila Melanogaster ◽  
Sperm Competition ◽  
Reproductive Tract ◽  
Seminal Fluid ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Link Type ◽  
Female Genotype ◽  
Mechanistic Basis

In many species, sperm can remain viable in the reproductive tract of a female well beyond the typical interval to remating. This creates an opportunity for sperm from different males to compete for oocyte fertilization inside the female’s reproductive tract. In Drosophila melanogaster, sperm characteristics and seminal fluid content affect male success in sperm competition. On the other hand, although genome-wide association studies (GWAS) have demonstrated that female genotype plays a role in sperm competition outcome as well, the biochemical, sensory, and physiological processes by which females detect and selectively use sperm from different males remain elusive. Here, we functionally tested 26 candidate genes implicated via a GWAS for their contribution to the female’s role in sperm competition, measured as changes in the relative success of the first male to mate (P1). Of these 26 candidates, we identified eight genes that affect P1 when knocked down in females, and showed that five of them do so when knocked down in the female nervous system. In particular, Rim knockdown in sensory pickpocket (ppk)+ neurons lowered P1, confirming previously published results, and a novel candidate, caup, lowered P1 when knocked down in octopaminergic Tdc2+ neurons. These results demonstrate that specific neurons in the female’s nervous system play a functional role in sperm competition and expand our understanding of the genetic, neuronal, and mechanistic basis of female responses to multiple matings. We propose that these neurons in females are used to sense, and integrate, signals from courtship or ejaculates, to modulate sperm competition outcome accordingly.

Post-Copulatory Sexual Selection

2021 ◽  
Author(s):  
Patricia L.R. Brennan ◽  
Dara N. Orbach
Keyword(s):  
Sexual Selection ◽  
Sperm Competition ◽  
Female Choice ◽  
Reproductive Tract ◽  
Seminal Fluid ◽  
Fertilization Success ◽  
Female Reproductive Tract ◽  
Cryptic Female Choice ◽  
Trade Offs ◽  
Morphological Criteria

The field of post-copulatory sexual selection investigates how female and male adaptations have evolved to influence the fertilization of eggs while optimizing fitness during and after copulation, when females mate with multiple males. When females are polyandrous (one female mates with multiple males), they may optimize their mating rate and control the outcome of mating interactions to acquire direct and indirect benefits. Polyandry may also favor the evolution of male traits that offer an advantage in post-copulatory male-male sperm competition. Sperm competition occurs when the sperm, seminal fluid, and/or genitalia of one male directly impacts the outcome of fertilization success of a rival male. When a female mates with multiple males, she may use information from a number of traits to choose who will sire her offspring. This cryptic female choice (CFC) to bias paternity can be based on behavioral, physiological, and morphological criteria (e.g., copulatory courtship, volume and/or composition of seminal fluid, shape of grasping appendages). Because male fitness interests are rarely perfectly aligned with female fitness interests, sexual conflict over mating and fertilization commonly occur during copulatory and post-copulatory interactions. Post-copulatory interactions inherently involve close associations between female and male reproductive characteristics, which in many species potentially include sperm storage and sperm movement inside the female reproductive tract, and highlight the intricate coevolution between the sexes. This coevolution is also common in genital morphology. The great diversity of genitalia among species is attributed to sexual selection. The evolution of genital attributes that allow females to maintain reproductive autonomy over paternity via cryptic female choice or that prevent male manipulation and sexual control via sexually antagonistic coevolution have been well documented. Additionally, cases where genitalia evolve through intrasexual competition are well known. Another important area of study in post-copulatory sexual selection is the examination of trade-offs between investments in pre-copulatory and post-copulatory traits, since organisms have limited energetic resources to allocate to reproduction, and securing both mating and fertilization is essential for reproductive success.

scholarly journals Structural variants and selective sweep foci contribute to insecticide resistance in the Drosophila melanogaster genetic reference panel

2018 ◽  
Author(s):  
Paul Battlay ◽  
Llewellyn Green ◽  
Pontus B. Leblanc ◽  
Joshua M. Schmidt ◽  
Alexandre Fournier-Level ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Transposable Element ◽  
Selective Sweep ◽  
Association Studies ◽  
Transcript Abundance ◽  
Reference Panel ◽  
Drosophila Genome ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Number Variation

AbstractPatterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweep loci to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome wide association studies map ‘survival-on-malathion’ to two of the largest sweeps in the D. melanogaster genome; Ace and Cyp6g1. Malathion survivorship also correlates with lines which have high levels of Cyp12d1 and Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived state seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility.

scholarly journals The power of a multivariate approach to genome-wide association studies: an example with Drosophila melanogaster wing shape

2017 ◽  
Author(s):  
William Pitchers ◽  
Jessica Nye ◽  
Eladio J. Márquez ◽  
Alycia Kowalski ◽  
Ian Dworkin ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Multivariate Analyses ◽  
Association Studies ◽  
Significant Snps ◽  
Wing Shape ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Phenotypic Effect ◽  
Genome Wide ◽  
Univariate Analyses

AbstractDue to the complexity of genotype-phenotype relationships, simultaneous analyses of genomic associations with multiple traits will be more powerful and more informative than a series of univariate analyses. In most cases, however, studies of genotype-phenotype relationships have analyzed only one trait at a time, even as the rapid advances in molecular tools have expanded our view of the genotype to include whole genomes. Here, we report the results of a fully integrated multivariate genome-wide association analysis of the shape of the Drosophila melanogaster wing in the Drosophila Genetic Reference Panel. Genotypic effects on wing shape were highly correlated between two different labs. We found 2,396 significant SNPs using a 5% FDR cutoff in the multivariate analyses, but just 4 significant SNPs in univariate analyses of scores on the first 20 principal component axes. A key advantage of multivariate analysis is that the direction of the estimated phenotypic effect is much more informative than a univariate one. Exploiting this feature, we show that the directions of effects were on average replicable in an unrelated panel of inbred lines. Effects of knockdowns of genes implicated in the initial screen were on average more similar than expected under a null model. Association studies that take a phenomic approach in considering many traits simultaneously are an important complement to the power of genomics. Multivariate analyses of such data are more powerful, more informative, and allow the unbiased study of pleiotropy.

scholarly journals Genome-wide association studies and contribution to cardiovascular physiology

2015 ◽  
Vol 47 (9) ◽  
pp. 365-375 ◽  
Author(s):  
Patricia B. Munroe ◽  
Andrew Tinker
Keyword(s):  
Complex Traits ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Cardiovascular Disorders ◽  
Genetic Associations ◽  
Physiological Processes ◽  
Genome Wide ◽  
Personal Interests

The study of family pedigrees with rare monogenic cardiovascular disorders has revealed new molecular players in physiological processes. Genome-wide association studies of complex traits with a heritable component may afford a similar and potentially intellectually richer opportunity. In this review we focus on the interpretation of genetic associations and the issue of causality in relation to known and potentially new physiology. We mainly discuss cardiometabolic traits as it reflects our personal interests, but the issues pertain broadly in many other disciplines. We also describe some of the resources that are now available that may expedite follow up of genetic association signals into observations on causal mechanisms and pathophysiology.

scholarly journals Structural variation in Drosophila melanogaster spermathecal ducts and its association with sperm competition dynamics

2020 ◽  
Vol 7 (3) ◽  
pp. 200130
Author(s):  
Ben R. Hopkins ◽  
Irem Sepil ◽  
Stuart Wigby
Keyword(s):  
Drosophila Melanogaster ◽  
Sperm Competition ◽  
Structural Variation ◽  
Reproductive Tract ◽  
Distal Portion ◽  
Mating Status ◽  
Spermathecal Duct ◽  
Male Sperm ◽  
Storage Organs ◽  
Single Mating

The ability of female insects to retain and use sperm for days, months, or even years after mating requires specialized storage organs in the reproductive tract. In most orders, these organs include a pair of sclerotized capsules known as spermathecae. Here, we report that some Drosophila melanogaster females exhibit previously uncharacterized structures within the distal portion of the muscular duct that links a spermatheca to the uterus. We find that these ‘spermathecal duct presences' (SDPs) may form in either or both ducts and can extend from the duct into the sperm-storing capsule itself. We further find that the incidence of SDPs varies significantly between genotypes, but does not change significantly with the age or mating status of females, the latter indicating that SDPs are not composed of or stimulated by sperm or male seminal proteins. We show that SDPs affect neither the number of first male sperm held in a spermatheca nor the number of offspring produced after a single mating. However, we find evidence that SDPs are associated with a lack of second male sperm in the spermathecae after females remate. This raises the possibility that SDPs provide a mechanism for variation in sperm competition outcome among females.

scholarly journals Leveraging biobank-scale rare and common variant analyses to identify ASPHD1 as the main driver of reproductive traits in the 16p11.2 locus

2019 ◽  
Author(s):  
Katrin Männik ◽  
Thomas Arbogast ◽  
Maarja Lepamets ◽  
Kaido Lepik ◽  
Anna Pellaz ◽  
...  
Keyword(s):  
Complex Traits ◽  
Reproductive Tract ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Interdisciplinary Approach ◽  
Copy Number Variant ◽  
Age At Menarche ◽  
Genome Wide Association Studies ◽  
Pubertal Onset ◽  
Causal Genes

AbstractWhereas genome-wide association studies (GWAS) allowed identifying thousands of associations between variants and traits, their success rate in pinpointing causal genes has been disproportionately low. Here, we integrate biobank-scale phenotype data from carriers of a rare copy-number variant (CNV), Mendelian randomization and animal modeling to identify causative genes in a GWAS locus for age at menarche (AaM). We show that the dosage of the 16p11.2 BP4-BP5 interval is correlated positively with AaM in the UK and Estonian biobanks and 16p11.2 clinical cohorts, with a directionally consistent trend for pubertal onset in males. These correlations parallel an increase in reproductive tract disorders in both sexes. In support of these observations, 16p11.2 mouse models display perturbed pubertal onset and structurally altered reproductive organs that track with CNV dose. Further, we report a negative correlation between the 16p11.2 dosage and relative hypothalamic volume in both humans and mice, intimating a perturbation in the gonadotropin-releasing hormone (GnRH) axis. Two independent lines of evidence identified candidate causal genes for AaM; Mendelian randomization and agnostic dosage modulation of each 16p11.2 gene in zebrafish gnrh3:egfp models. ASPHD1, expressed predominantly in brain and pituitary gland, emerged as a major phenotype driver; and it is subject to modulation by KCTD13 to exacerbate GnRH neuron phenotype. Together, our data highlight the power of an interdisciplinary approach to elucidate disease etiologies underlying complex traits.

Molecular genetic analysis of multiple sclerosis

2020 ◽  
pp. 80-81
Author(s):  
Я.Р. Тимашева ◽  
Т.Р. Насибуллин ◽  
И.А. Туктарова ◽  
В.В. Эрдман ◽  
Т.Р. Галиуллин ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Association Studies ◽  
Molecular Genetic Analysis ◽  
Genome Wide Association ◽  
Control Group ◽  
Polymorphism Analysis ◽  
Genome Wide Association Studies ◽  
Genome Wide

Рассеянный склероз - это хроническое воспалительное демиелинизирующее заболевание центральной нервной системы многофакторной природы. Цель настоящего исследования состояла в проведении анализа ассоциаций с заболеванием полиморфных маркеров в генах, продукты которых предположительно участвуют в патогенезе заболевания, а также идентифицированных в результате проведения полногеномных исследований, в популяциях башкир, русских и татар, проживающих в Республике Башкортостан. В результате проведенного исследования нами получены данные, подтверждающие ассоциацию с рассеянным склерозом генов, продукты которых участвуют в развитии аутоиммунного воспаления центральной нервной системы. Multiple sclerosis is a chronic inflammatory demyelinating disorder of central nervous system of multifactorial origin. Genome-wide association studies identified 700 polymorphic genetic variants associated with multiple sclerosis. The aim of the current study was to analyse associations of the polymorphic markers in genes involved in the pathogenesis of the disease and those identified by genome-wide association studies in the populations of Bashkirs, Russians, and Tatars from the Republic of Bashkortostan (Russian Federation). The study group was comprised of 644 patients with multiple sclerosis and 1408 control group individuals. Genotyping of 35 polymorphic genetic markers was performed using allele-specific PCR and PCR followed by restriction fragment length polymorphism analysis. The data obtained in our study confirm the association with multiple sclerosis of the genes involved in the development of autoimmune inflammation in central nervous system.

scholarly journals The Obesity-Linked Gene Nudt3 Drosophila Homolog Aps Is Associated With Insulin Signaling

2015 ◽  
Vol 29 (9) ◽  
pp. 1303-1319 ◽  
Author(s):  
Michael J. Williams ◽  
Anders Eriksson ◽  
Muksheed Shaik ◽  
Sarah Voisin ◽  
Olga Yamskova ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Insulin Signaling ◽  
Association Studies ◽  
Neurosecretory Cells ◽  
Genome Wide Association Studies ◽  
Nudix Hydrolase ◽  
The Central Nervous System ◽  
Carbohydrate Levels ◽  
Median Neurosecretory Cells

Abstract Several genome-wide association studies have linked the Nudix hydrolase family member nucleoside diphosphate-linked moiety X motif 3 (NUDT3) to obesity. However, the manner of NUDT3 involvement in obesity is unknown, and NUDT3 expression, regulation, and signaling in the central nervous system has not been studied. We performed an extensive expression analysis in mice, as well as knocked down the Drosophila NUDT3 homolog Aps in the nervous system, to determine its effect on metabolism. Detailed in situ hybridization studies in the mouse brain revealed abundant Nudt3 mRNA and protein expression throughout the brain, including reward- and feeding-related regions of the hypothalamus and amygdala, whereas Nudt3 mRNA expression was significantly up-regulated in the hypothalamus and brainstem of food-deprived mice. Knocking down Aps in the Drosophila central nervous system, or a subset of median neurosecretory cells, known as the insulin-producing cells (IPCs), induces hyperinsulinemia-like phenotypes, including a decrease in circulating trehalose levels as well as significantly decreasing all carbohydrate levels under starvation conditions. Moreover, lowering Aps IPC expression leads to a decreased ability to recruit these lipids during starvation. Also, loss of neuronal Aps expression caused a starvation susceptibility phenotype while inducing hyperphagia. Finally, the loss of IPC Aps lowered the expression of Akh, Ilp6, and Ilp3, genes known to be inhibited by insulin signaling. These results point toward a role for this gene in the regulation of insulin signaling, which could explain the robust association with obesity in humans.

scholarly journals Genetic coordination of sperm morphology and seminal fluid proteins promotes male reproductive success in Drosophila melanogaster

2021 ◽  
Author(s):  
Jake Galvin ◽  
Erica Larson ◽  
Sevan Yedigarian ◽  
Mohammad Rahman ◽  
Kirill Borziak ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Reproductive Success ◽  
Sperm Competition ◽  
Seminal Fluid ◽  
Fertilization Success ◽  
Male Reproductive Success ◽  
Sperm Length ◽  
Seminal Fluid Proteins ◽  
Female Remating ◽  
Paternity Success

Spermatozoal morphology is highly variable both among and within species and in ways that can significantly impact fertilization success. In Drosophila melanogaster, paternity success depends on sperm length of both competing males and length of the female's primary sperm storage organ. We found that genes upregulated in long sperm testes are enriched for lncRNAs and seminal fluid proteins (Sfps). Transferred in seminal fluid to the female during mating, Sfps are secreted by the male accessory glands (AG) and affect female remating rate, physiology, and behavior with concomitant advantages for male reproductive success. Despite being upregulated in long sperm testes, they have no known function in testis tissue. We found that Sex Peptide and ovulin (Acp26Aa) knockouts resulted in shorter sperm, suggesting that Sfps may regulate sperm length during spermatogenesis. However, knockout of AG function did not affect sperm length, suggesting that AG expression has no influence on spermatogenic processes. We also found that long sperm males are better able to delay female remating, suggesting higher Sfp expression in AG. These results might suggest that long sperm males have a double advantage in sperm competition by both delaying female remating, likely through transfer of more Sfps, and by resisting sperm displacement. However, we also found that this extra advantage does not necessarily translate to more progeny or higher paternity success. Thus, we found that multiple components of the ejaculate coordinate to promote male reproductive success at different stages of reproduction, but the realized fitness advantages in sperm competition are uncertain.

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