Hyper Sperm
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Hyper Sperm
Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca²⁺ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animallineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca²⁺ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior.
The entire CatSper complex evolves adaptively in primates. (A) The CatSper complex evolves under positive selection in almost every lineage in the primate phylogeny. For each CatSper gene, branches where dN/dS >1 are highlighted with a color corresponding to each gene. In cases where multiple genes have a dN/dS >1 for a single branch, the colors are stacked. (B) We detect specific sites under selection in almost every CatSper gene. Extracellular domains are marked as dark segments and intracellular domains as light segments. Orange arrows indicate the sites under selection by the Bayes-EmpiricalBayes test in PAML, with a posterior-probability >0.90 (Yang et al. 2005). Selected sites grouped close together are labeled with a bar specifying the number of sites under selection. The number of extracellular and intracellular sites under selection for each gene are tabulated.
pkd2 evolves adaptively in Drosophila. (A) Fixed nonsynonymous fixed differences between D. melanogaster and D. simulans are marked with purple arrows above the domain structure. Clusters of fixed nonsynonymous changes are labeled with a bar specifying the number of sites. Polymorphic nonsynonymous changes within each species are marked below the domain structure. The gene span of Drosophila pkd2 is annotated as a grey bar with blue rectangles marking the transmembrane domains and a green box marking the coiled-coil domain. Extracellular and intracellular domains are in different shades of grey. (B) McDonald-Kreitman tests show that Drosophila pkd2 evolves under positive selection between D. melanogaster and D. simulans, and this signal is generated by changes in the extracellular domain. The MK table details nonsynonymous fixed (Nf), synonymous fixed (Sf), nonsynonymous polymorphic (Np), and synonymous polymorphic (Sp) sites. We report the Fisher's exact (FE) P value, and the alpha-value for each segment of the gene. (C) A polarized McDonald-Kreitman test for the extracellular domain of Drosophila pkd2 demonstrates that this region evolves under positive selection along both lineages. Fixed changes were polarized to the D. melanogaster or D. simulans lineages using D. yakuba as an outgroup species. (D) NSsites model tests using PAML show that Drosophila pkd2 evolves adaptively across many species of Drosophila.
A predicted structural model of Drosophila pkd2 shows that nonsynonymous changes between D. melanogaster and D. simulans reside on the extracellular faces. (A) The homo-tetramer of our predicted Drosophila pkd2 structure. The 2-D gene diagram is shaded for the region that could be successfully modeled. The monomers are alternated in shades of grey for contrast. The extracellular loop of one monomer is colored blue. The diagram to the right describes the orientation of the channel. (B) Sites that diverge between D. melanogaster and D. simulans are on the extracellular region of the channel. The base of the monomer is grey, and the extracellular region is blue. The nonsynonymous changes between the two species shown in yellow.
Both intermale sperm competition and female choice can drive the rapid evolution of the sperm hyper-activation channels. (A) Males that secrete seminal peptides that block the hyper-activation channels of sperm from competing males gain a selective advantage. (B) Females may secrete peptides that inhibit sperm hyper-activation channels to control fertilization rates. Males that can prevent the inhibition of sperm hyperactivation gain a selective advantage.
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Content may be subject to copyright.
Parallel Evolution of Sperm Hyper-Activation Ca
Department of Biology, University of Utah
* Corresponding author: E-mail: jacob.cooper @ utah.edu.
Data deposition: This project has been deposited at GenBank under the a ccession # KY990034-KY990049
Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the
egg. The mechanism of sperm hyper-activat ion in many metazoans, including humans, consists of a jolt of Ca
flagellum via CatSper ion channels. Surprisingly , all nine CatSper genes have been independently lost in several animal lineage s.
In Drosophila , sperm hyper-activation is performed through the cooption of the polycystic kid ney disease 2 ( pkd2 )C a
channel. The parallels between CatSpers in primates and pkd 2 in Drosophila provide a unique opportunity to exami ne the
molecular evolution of the sperm hyper-activa tion machinery in two independent, nonhomologo us calcium channels sepa-
rated by > 500 million years of divergence. He re, we use a comprehensive phylogenomic app roach to investigate the selective
pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under
recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptiv e evolution in Drosophila .
Third, we show that this adaptive evolution of pkd2 is drive n by its role in sperm hyper-activation. These patte rns of selection
suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflic t with antagonistic ligands that
modulate channel activity. Together, our results add sperm hyper-ac tivation channels to the class of fast evolving reproductive
proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior .
Key words: sexual conflict, sperm hyper-a ctivation, CatSper, reproductive pro teins, parallel evolution, ev olutionary
Sexual conflict shapes sperm development and sperm dynam-
ics ( Swanson and Vacquier 2002 ; Clark et al. 2006 ; Turner
et al. 2008 ; Wilburn and Swanson 2016 ). Both male–female
interactions and intermale comp etition drive rapid changes in
male reproductive proteins, whose constant innovation has
been likened to a molecular arms race. These rapid changes in
reproductive proteins have the pot ential to establish barriers
to fertilization between populations and lead to the evolution
of new species ( Parker and Partridge 1998 ; Gavrilets 2000 ;
Howard et al. 2009 ; Moyle et al. 2014 ). The best-known
examples of this phenomenon include the rapid evolution
of reproductive proteins in abalone, mammals, and
Drosophila ( Lee et al. 1995 ; Swanson and Vacquier 1997 ;
Kresge et al. 2001 ; Swanson et al. 2003 ; Gomendio et al.
2006 ; Clark et al. 2007 ; Hamm et al. 2007 ; Findlay et al.
2014 ; Vicens et al. 2015 ). Molecular evolutionary studies on
how sexual conflicts shape reproductive proteins have fo-
cused on several aspects of sperm biology such as direct
sperm-egg interactions, seminal fluid proteins and sperm be-
havior ( Swanson and Vacquier 2002 ; Panhuis et al. 2006 ;
Fisher et al. 2016 ). Here, we uncover the patterns of molec-
ular evolution of the sperm hyper-activation machinery in
animals, which remains a fundamental but largely unexplored
When spermatogenesis is complete, the resulting mature
sperm are motile but quiescent. After copulation, however,
sperm cease normal swimming and burst into a sprint. This
dramatic postmating accelerat ion of sperm is known as sperm
hyper-activation ( Suarez et al. 1991 ). Sperm hyper-activation
was first observed in mammals through studies on the golden
hamster ( Yanagimachi 1969 , 1970 ), and has since been since
described in many other taxa ( Cosson et al. 2008 ; Suarez and
Ho 2003 ). When sperm hyper-activate, they go through a
cellular change that alters the motion of the sperm flagellum
from a slow, low amplitude, sy mmetric beat to a whip-like,
high amplitude, asymmetric beat ( Ooi et al. 2014 ). This tran-
sition is not subtle; hyper-activated sperm swimming at top
ß The Author 2017. Published by Oxford Unive rsity Press on behalf of the Society for Molecular Bio logy and Evolution.
This is an Open Access article d istributed under the terms of the Creative Commons Attribution Non-Commercial License( ht tp://creativecommons.org/licenses/by-nc/ 4.0/ ), which permits
non-commercial re-use, distribution, a nd reproduction in any medium, provided the original work is properly cited. For co mmercial re-use, please c ontact journals.per missions@oup.com
1938 Genome Biol. Evol. 9(7):1938–1949. doi:10.1093/gbe/evx131 Advance Access publication July 11, 2017
... Instead, it is known in that the transient receptor potential polycystic (TRPP)2/polycystic kidney disease (PKD)2 channel is essential for sperm flagellar beat regulation [57,58]. It has been reported that the genes encoding PKD2 channels in fruit flies have notable diversity (indicating rapid evolution) between two closely related species compared with other housekeeping genes [59] . This observation is a typical feature of proteins involved in sexual reproduction [60,61] including CatSper [59,62,63]. ...
... It has been reported that the genes encoding PKD2 channels in fruit flies have notable diversity (indicating rapid evolution) between two closely related species compared with other housekeeping genes [59]. This observation is a typical feature of proteins involved in sexual reproduction [60,61] including CatSper [59, 62,63]. Because Ca 2+ plays a fundamental role in flagellar beat regulation, species that lack CatSper should have their own substitute for CatSper. ...
Background:
CatSper is a sperm-specific calcium ion (Ca2+) channel, which regulates sperm flagellar beating by tuning cytoplasmic Ca2+ concentrations. Although this Ca2+ channel is essential for mammalian fertilization, recent bioinformatics analyses have revealed that genes encoding CatSper are heterogeneously distributed throughout the eukaryotes, including vertebrates. As this channel is activated by cytoplasmic alkalization in mammals and sea urchins, it has been proposed that the sperm-specific Na+/H+ exchanger (sNHE, a product of the SLC9C gene family) positively regulates its activity. In mouse, sNHE is functionally coupled to soluble adenylyl cyclase (sAC). CatSper, sNHE, and sAC have thus been considered functionally interconnected in the control of sperm motility, at least in mouse and sea urchin.
Results:
We carried out a comparative genomic analysis to explore phylogenetic relationships among CatSper, sNHE and sAC in eukaryotes. We found that sNHE occurs only in Metazoa, although sAC occurs widely across eukaryotes. In animals, we found correlated and restricted distribution patterns of the three proteins, suggesting coevolution among them in the Metazoa. Namely, nearly all species in which CatSper is conserved also preserve sNHE and sAC. In contrast, in species without sAC, neither CatSper nor sNHE is conserved. On the other hand, the distribution of another testis-specific NHE (NHA, a product of the SLC9B gene family) does not show any apparent association with that of CatSper.
Conclusions:
Our results suggest that CatSper, sNHE and sAC form prototypical machinery that functions in regulating sperm flagellar beating in Metazoa. In non-metazoan species, CatSper may be regulated by other H+ transporters, or its activity might be independent of cytoplasmic pH.
... We found that the rate of nonsynonymous substitutions (dN/dS) between D. melanogaster and D. simulans is significantly elevated over the null expectation in SMC3, Cap-D2, and Cap-D3. To validate these results, further analyses for signatures of positive selection were conducted according to the method described in Cooper and Phadnis (2017) . Briefly, we analyzed rates of evolution for all condensin and cohesin complex subunits in 17 species of Drosophila, 16 species of primates, and 6-14 species within other mammal clades. ...
... We have not applied a multiple testing correction to our results, because it is not clear that analyzing different subunits represents multiple testing of the same hypothesis. This is concordant with the methods in previous studies using McDonald-Kreitman tests and PAML analysis to detect positive selection in protein complexes (Presgraves and Stephan 2007;Daugherty et al. 2014; Cooper and Phadnis 2017) . See supplementary fig. ...
Condensins play a crucial role in the organization of genetic material by compacting and disentangling chromosomes. Based on studies in a few model organisms, the condensin I and condensin II complexes are considered to have distinct functions, with the condensin II complex playing a role in meiosis and somatic pairing of homologous chromosomes in Drosophila. Intriguingly, the Cap-G2 subunit of condensin II is absent in Drosophila melanogaster, and this loss may be related to the high levels of chromosome pairing seen in flies. Here, we find that all three non-SMC subunits of condensin II (Cap-G2, Cap-D3, and Cap-H2) have been repeatedly and independently lost in taxa representing multiple insect orders, with some taxa lacking all three. We also find that all non-Dipteran insects display near-uniform low pairing levels regardless of their condensin II complex composition, suggesting that some key aspects of genome organization are robust to condensin II subunit losses. Finally, we observe consistent signatures of positive selection in condensin subunits across flies and mammals. These findings suggest that these ancient complexes are far more evolutionarily labile than previously suspected, and are at the crossroads of several forms of genomic conflicts. Our results raise fundamental questions about the specific functions of the two condensin complexes in taxa that have experienced subunit losses, and open the door to further investigations to elucidate the diversity of molecular mechanisms that underlie genome organization across various life forms.
... Our comparison between clades then relies on the fact that we used the same method of detection in every case, not that our data represents a ground truth about recurrent positive selection. Encouragingly, our data set identifies several previously studied examples of recurrent positive selection in at least one clade: for example, OAS1 [31], PKR [4], TFRC [3], IZUMO1 and IZUMO4 [32], PARP4 and PARP15 [6], CATSPER 1-4, D, G, and E [33] , RNASEL [34], ZP3 [35], and CGAS [5]. We compared our results with a list of genes representing the most heavily enriched genes for selected sites from a previous genome-wide scan in primates and found that MUC13, NAPSA, PTPRC, APOL6, MS4A12, SCGB1D2, PIP, CFH, RARRES3, OAS1, and TSPAN8 were detected under recurrent positive selection in at least one clade, while our analysis missed PASD1, CD59, and TRIM (11 / 14 genes) [12]. ...
... To identify gene sequences throughout each clade, we developed a search method that utilizes the CDS sequence of one well-annotated species in that clade. This method was slightly modified to be a whole genome scale version of a previous method we used to study positive selection for a much smaller group of genes [33] . We started with a list of all protein-coding CDS sequences for our reference species. ...
Recurrent positive selection at the codon level is often a sign that a gene is engaged in a molecular arms race - a conflict between the genome of its host and the genome of another species over mutually exclusive access to a resource that has a direct effect on the fitness of both individuals. Detecting molecular arms races has led to a better understanding of how evolution changes the molecular interfaces of proteins when organisms compete over time, especially in the realm of host-pathogen interactions. Here, we present a method for detection of gene-level recurrent positive selection across entire genomes for a given phylogenetic group. We deploy this method on five mammalian clades - primates, mice, deer mice, dogs, and bats - to both detect novel instances of recurrent positive selection and to compare the prevalence of recurrent positive selection between clades. We analyze the frequency at which individual genes are targets of recurrent positive selection in multiple clades. We find that coincidence of selection occurs far more frequently than expected by chance, indicating that all clades experience shared selective pressures. Additionally, we highlight Polymeric Immunoglobulin Receptor (PIGR) as a gene which shares specific amino acids under recurrent positive selection in multiple clades, indicating that it has been locked in a molecular arms race for ~100My. These data provide an in-depth comparison of recurrent positive selection across the mammalian phylogeny, and highlights of the power of comparative evolutionary approaches to generate specific hypotheses about the molecular interactions of rapidly evolving genes.
... One known example of this comes from the mussel M. galloprovincialis, where FRF has been shown to induce modifications on the sperm surface glycans [77] and hence affect the acrosome reaction to favour specific males at fertilization [78]. Chemical and biochemical components of FRF may interact in influencing sperm performance, as FRF Ca 2+ concentration and FRF proteins may interact to modulate the activity of Ca 2+ sperm-specific channels such as CatSper and pdk2, ultimately affecting sperm hyper-activation [79] . FRF can also affect competitive fertilization success by interacting with seminal fluid in addition to, or instead of, the sperm. ...
The role of non-gametic components of the ejaculate (seminal fluid) in fertility and sperm competitiveness is now well established. Surprisingly, however, we know far less about female reproductive fluid (FRF) in the context of sexual selection, and insights into male–FRF interactions in the context of sperm competition have only recently emerged. Despite this limited knowledge, evidence from taxonomically diverse species has revealed insights into the effects of FRF on sperm traits that have previously been implicated in studies of sperm competition. Specifically, through the differential effects of FRF on a range of sperm traits, including chemoattraction and alterations in sperm velocity, FRF has been shown to exert positive phenotypic effects on the sperm of males that are preferred as mating partners, or those from the most compatible or genetically diverse males. Despite these tantalizing insights into the putative sexually selected functions of FRF, we largely lack a mechanistic understanding of these processes. Taken together, the evidence presented here highlights the likely ubiquity of FRF-regulated biases in fertilization success across a diverse range of taxa, thus potentially elevating the importance of FRF to other non-gametic components that have so far been studied largely in males.
This article is part of the theme issue ‘Fifty years of sperm competition'.
... The results of our structural alignments suggest a strong functional relationship among all the Cat-Sper proteins evaluated due to the low RSMD and high TM-scores obtained. Given that the function of CatSper proteins as ion channels of Homo sapiens (Cooper and Phadnis, 2017) and Mus musculus (Vicens et al., 2014) are well known, according to this result the same function is encoded by CatSper proteins from Salmo salar. ...
Among all the Ca2+ channels, CatSper channels have been one of the most studied in sperm of different species due to their demonstrated role in the fertilization process. In fish sperm, the calcium channel plays a key role in sperm activation. However, the functionality of the CatSper channels has not been studied in any of the fish species. For the first time, we studied the relationship of the CatSper channel with sperm motility in a fish, using Atlantic salmon (Salmo salar) as the model. The results of our study showed that the CatSper channel in Salmo salar has chemical-physical characteristics similar to those reported for mammalian CatSper channels. In this work, it was shown that Salmo salar CatSper 3 protein has a molecular weight of approximately 55-kDa similar to Homo sapiens CatSper 3. In silico analyses suggest that this channel forms a heterotetramer sensitive to the specific inhibitor HC-056456, with a binding site in the center of the pore of the CatSper channel, hindering or preventing the influx of Ca2+ ions. The in vitro assay of the sperm motility inhibition of Salmo salar with the inhibitor HC-056456 showed that sperm treated with this inhibitor significantly reduced the total and progressive motility (p < .0001), demonstrating the importance of this ionic channel for this cell. The complementation of the in silico and in vitro analyses of the present work demonstrates that the CatSper channel plays a key role in the regulation of sperm motility in Atlantic salmon.
... In drosophila model, PKD2 cation channel on sperm flagellum has been implicated in modulating the directional sperm movement inside the female reproductive tract [68], and appears to have compensated for the loss of CatSper ion channels to trigger the sperm hyperactivation. However, primate PKD2 has no role in sperm hyperactivation [69] . Moreover, PKD2 calcium channel is also reportedly involved in adopting the correct flagellar waveform and wave propagation direction of drosophila sperm [70]. ...
Due to lower farrowing rate and reduced litter size with frozen-thawed semen, over 90% of artificial insemination (AI) is conducted using liquid stored boar semen. Although substantial progress has been made towards optimizing the cryopreservation protocols for boar sperm, the influencing factors and underlying mechanisms related to cryoinjury and freeze tolerance of boar sperm remain largely unknown. In this study, we report the differential expression of mRNAs and miRNAs between fresh and frozen-thawed boar sperm using high-throughput RNA sequencing. Our results showed that 567 mRNAs and 135 miRNAs were differentially expressed (DE) in fresh and frozen-thawed boar sperm. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the majority of DE mRNAs were enriched in environmental information processing such as cytokine-cytokine receptor interactions, PI3K-Akt signaling, cell adhesion, MAPK, and calcium signaling pathways. Moreover, the targets of DE miRNAs were enriched in significant GO terms such as cell process, protein binding, and response to stimuli. In conclusion, we speculate that DE mRNAs and miRNAs are heavily involved in boar sperm response to environment stimuli, apoptosis, and metabolic activities. The differences in expression also reflect the various structural and functional changes in sperm during cryopreservation.
... We might expect transcription of these genes to evolve quickly [42], as their products permit adaptation to new environments on a cellular level. Additionally, some types of these transport mechanisms have been implicated in genetic conflict [43, 44] and could thus be expected to evolve quickly. The other categories of transcript abundance changes (stage 5 losses, stage 2 gains, stage 2 losses) had no significant enrichment of gene ontology categories compared to the rest of the genes with transcripts present at that stage. ...
The earliest stage of animal development is controlled by maternally deposited mRNA transcripts and proteins. Once the zygote is able to transcribe its own genome, maternal transcripts are degraded, in a tightly regulated process known as the maternal to zygotic transition (MZT). While this process has been well-studied within model species, we have little knowledge of how the pools of maternal and zygotic transcripts evolve. To characterize the evolutionary dynamics and functional constraints on early embryonic expression, we created a transcriptomic dataset for 14 Drosophila species spanning over 50 million years of evolution, at developmental stages before and after the MZT, and compared our results with a previously published Aedes aegypti developmental time course. We found deep conservation over 250 million years of a core set of genes transcribed only by the zygote. This select group is highly enriched in transcription factors that play critical roles in early development. However, we also identify a surprisingly high level of change in the transcripts represented at both stages over the phylogeny. While mRNA levels of genes with maternally deposited transcripts are more highly conserved than zygotic genes, those maternal transcripts that are completely degraded at the MZT vary dramatically between species. We also show that hundreds of genes have different isoform usage between the maternal and zygotic genomes. Our work suggests that maternal transcript deposition and early zygotic transcription are remarkably dynamic over evolutionary time, despite the widespread conservation of early developmental processes.
... We found that the rate of nonsynonymous substitutions (dN/dS) between D. melanogaster and D. simulans is significantly elevated over the null expectation in these subunits: SMC3 in cohesin, Cap-D2 in condensin I, and Cap-D3 in condensin II. To validate these results, further analyses for signatures of positive selection were conducted according to the method described in Cooper and Phadnis (48) . Briefly, we analyzed rates of evolution for all condensin and cohesin complex subunits in 17 species of Drosophila, 16 species of primates, and 6-14 species within other mammal clades. ...
Condensins play a crucial role in the organization of genetic material by compacting and disentangling chromosomes. The condensin I and condensin II complexes are widely considered to have distinct functions based on studies in a few model organisms, although the specific functions of each complex are yet to be fully understood. The condensin II complex is critical for genome organization in Drosophila, and is a key anti-pairing factor that separates homologous chromosomes in somatic cells. Intriguingly, the Cap-G2 subunit of condensin II is absent in Drosophila melanogaster, and this loss may be related to the high levels of homologous chromosome pairing in somatic cells seen in flies. Here, we find that this Cap-G2 loss predates the origin of Dipterans, and other CapG2 losses have occurred independently in multiple insect lineages. Furthermore, the Cap-H2 and Cap-D3 subunits have also been repeatedly and independently lost in several insect orders, and some taxa lack condensin II-specific subunits entirely. We used Oligopaint DNA-FISH to quantify pairing levels in ten species across seven orders, representing several different configurations of the condensin II complex. We find that all non-Dipteran insects display near-uniform low pairing levels, suggesting that some key aspects of genome organization are robust to condensin II subunit losses. Finally, we observe consistent signatures of positive selection in condensin II subunits across flies and mammals. These findings suggest that these ancient complexes are far more evolutionarily labile than previously suspected, and are at the crossroads of several forms of genomic conflicts. Our results raise fundamental questions about the specific functions of the two condensin complexes and the interplay between them in taxa that have experienced subunit losses, and open the door to further investigations to elucidate the diversity of molecular mechanisms that underlie genome organization across various life forms.
To overcome egg protective vestments and ensure successful fertilization, mammalian spermatozoa switch symmetrical progressive motility to a powerful, whip-like flagellar motion, known as hyperactivation. The latter is triggered by a calcium influx through the sperm-specific, voltage-dependent, and alkalization-activated calcium channel of sperm - CatSper. The channel comprises nine subunits which together form a heteromeric complex. CatSper-deficient male mice and men with mutations in CatSper genes are infertile. This calcium channel is regulated by various endogenous compounds, such as steroids, prostaglandins, endocannabinoids, and intracellular pH. Being a sperm-specific ion channel that is not expressed anywhere else in the body, CatSper represents an ideal target for the development of female and even male contraceptives. In this review, we discuss the recent advances in studying CatSper functional properties and discuss future steps that are required to take in order to achieve a deep understanding of the molecular basis of CatSper function.
Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca ²⁺ into the sperm flagellum via CatSper ion channels. Surprisingly, CatSper genes have been independently lost in several animal lineages. In Drosophila , sperm ... [Show full abstract] hyper-activation is performed through the co-option of the polycystic kidney disease 2 ( Dpkd2 ) Ca ²⁺ channel. The parallels between CatSpers in primates and Dpkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by more than 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila . Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior.
February 2018 · Current Opinion in Physiology
To overcome egg protective vestments and ensure successful fertilization, mammalian spermatozoa switch symmetrical progressive motility to a powerful, whip-like flagellar motion, known as hyperactivation. The latter is triggered by a calcium influx through the sperm-specific, voltage-dependent, and alkalization-activated calcium channel of sperm - CatSper. The channel comprises nine subunits ... [Show full abstract] which together form a heteromeric complex. CatSper-deficient male mice and men with mutations in CatSper genes are infertile. This calcium channel is regulated by various endogenous compounds, such as steroids, prostaglandins, endocannabinoids, and intracellular pH. Being a sperm-specific ion channel that is not expressed anywhere else in the body, CatSper represents an ideal target for the development of female and even male contraceptives. In this review, we discuss the recent advances in studying CatSper functional properties and discuss future steps that are required to take in order to achieve a deep understanding of the molecular basis of CatSper function.
Recurrent positive selection at the codon level is often a sign that a gene is engaged in a molecular arms race - a conflict between the genome of its host and the genome of another species over mutually exclusive access to a resource that has a direct effect on the fitness of both individuals. Detecting molecular arms races has led to a better understanding of how evolution changes the molecular ... [Show full abstract] interfaces of proteins when organisms compete over time, especially in the realm of host-pathogen interactions. Here, we present a method for detection of gene-level recurrent positive selection across entire genomes for a given phylogenetic group. We deploy this method on five mammalian clades - primates, mice, deer mice, dogs, and bats - to both detect novel instances of recurrent positive selection and to compare the prevalence of recurrent positive selection between clades. We analyze the frequency at which individual genes are targets of recurrent positive selection in multiple clades. We find that coincidence of selection occurs far more frequently than expected by chance, indicating that all clades experience shared selective pressures. Additionally, we highlight Polymeric Immunoglobulin Receptor (PIGR) as a gene which shares specific amino acids under recurrent positive selection in multiple clades, indicating that it has been locked in a molecular arms race for ~100My. These data provide an in-depth comparison of recurrent positive selection across the mammalian phylogeny, and highlights of the power of comparative evolutionary approaches to generate specific hypotheses about the molecular interactions of rapidly evolving genes.
Uncovering the genetic and molecular basis of barriers to gene flow between populations is key to understanding how new species are born. Intrinsic postzygotic reproductive barriers such as hybrid sterility and hybrid inviability are caused by deleterious genetic interactions known as hybrid incompatibilities. The difficulty in identifying these hybrid incompatibility genes remains a ... [Show full abstract] rate-limiting step in our understanding of the molecular basis of speciation. We recently described how whole genome sequencing can be applied to identify hybrid incompatibility genes, even from genetically terminal hybrids. Using this approach, we discovered a new hybrid incompatibility gene, gfzf, between Drosophila melanogaster and Drosophila simulans, and found that it plays an essential role in cell cycle regulation. Here, we discuss the history of the hunt for incompatibility genes between these species, discuss the molecular roles of gfzf in cell cycle regulation, and explore how intragenomic conflict drives the evolution of fundamental cellular mechanisms that lead to the developmental arrest of hybrids.
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Hyperspermia: Symptoms, Causes, Fertility, and More
(PDF) Parallel Evolution of Sperm Hyper -Activation Ca Channels
GitHub - hyperopt/hyperopt: Distributed Asynchronous Hyperparameter...
Sperm vs Hyperactivation - What's the difference? | WikiDiff
Hyperspermia: Symptoms, treatments, and causes
timgates42
docs: fix simple typo, fagile -> fragile ( #774 )
Cache dependencies pre-commit workflow
docs: fix simple typo, fagile -> fragile ( #774 )
Add markdown tutorial to docs ( #693 )
ignore: ignore jupyternotebook cache
Travis CI: Add Python 3.9 to the testing ( #759 )
Add universal flag for building wheels
# define an objective function
def objective ( args ):
case , val = args
if case == 'case 1' :
return val
else :
return val ** 2
# define a search space
from hyperopt import hp
space = hp . choice ( 'a' ,
[
( 'case 1' , 1 + hp . lognormal ( 'c1' , 0 , 1 )),
( 'case 2' , hp . uniform ( 'c2' , - 10 , 10 ))
])
# minimize the objective over the space
from hyperopt import fmin , tpe , space_eval
best = fmin ( objective , space , algo = tpe . suggest , max_evals = 100 )
print ( best )
# -> {'a': 1, 'c2': 0.01420615366247227}
print ( space_eval ( space , best ))
# -> ('case 2', 0.01420615366247227}
$ git clone https://github.com/ < github username > /hyperopt.git
$ cd hyperopt
pip install -e .[MongoTrials]
pip install -e .[SparkTrials]
pip install -e .[ATPE]
pip install -e .[dev]
$ git checkout master
$ git pull upstream master
$ git add modified_files
$ git commit -m " my first hyperopt commit "
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If you're a developer and wish to contribute, please follow these steps:
Create an account on GitHub if you do not already have one.
Fork the project repository: click on the ‘Fork’ button near the top of the page. This creates a copy of the code under your account on the GitHub user account. For more details on how to fork a repository see this guide .
Clone your fork of the hyperopt repo from your GitHub account to your local disk:
Create environment with:
$ python3 -m venv my_env or $ python -m venv my_env
or with conda:
$ conda create -n my_env python=3
Activate the environment:
$ source my_env/bin/activate
or with conda:
$ conda activate my_env
Install dependencies for extras (you'll need these to run pytest):
Linux/UNIX:
$ pip install -e '.[MongoTrials, SparkTrials, ATPE, dev]'
Add the upstream remote. This saves a reference to the main hyperopt repository, which you can use to keep your repository synchronized with the latest changes:
$ git remote add upstream https://github.com/hyperopt/hyperopt.git
You should now have a working installation of hyperopt, and your git repository properly configured. The next steps now describe the process of modifying code and submitting a PR:
Synchronize your master branch with the upstream master branch:
Create a feature branch to hold your development changes:
and start making changes. Always use a feature branch. It’s good practice to never work on the master branch!
We recommend to use Black to format your code before submitting a PR which is installed automatically in step 4.
Then, once you commit ensure that git hooks are activated (Pycharm for example has the option to omit them). This will run black automatically on all files you modified, failing if there are any files requiring to be blacked. In case black does not run execute the following:
Develop the feature on your feature branch on your computer, using Git to do the version control. When you’re done editing, add changed files using git add and then git commit:
The tests for this project use PyTest and can be run by calling pytest .
Record your changes in Git, then push the changes to your GitHub account with:
Note that dev dependencies require python 3.6+.
Currently three algorithms are implemented in hyperopt:
Hyperopt has been designed to accommodate Bayesian optimization algorithms based on Gaussian processes and regression trees, but these are not currently implemented.
All algorithms can be parallelized in two ways, using:
Hyperopt documentation can be found here , but is partly still hosted on the wiki. Here are some quick links to the most relevant pages:
If you use this software for research, please cite the paper ( http://proceedings.mlr.press/v28/bergstra13.pdf ) as follows:
Bergstra, J., Yamins, D., Cox, D. D. (2013) Making a Science of Model Search: Hyperparameter Optimization in Hundreds of Dimensions for Vision Architectures. TProc. of the 30th International Conference on Machine Learning (ICML 2013), June 2013, pp. I-115 to I-23.
This project has received support from
Distributed Asynchronous Hyperparameter Optimization in Python
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