scholarly journals Parallel evolution of sperm hyper-activation Ca2+ channels

2017 ◽  
Author(s):  
Jacob C. Cooper ◽  
Nitin Phadnis
Keyword(s):  
Molecular Evolution ◽  
Adaptive Evolution ◽  
Parallel Evolution ◽  
Channel Activity ◽  
Polycystic Kidney ◽  
Reproductive Proteins ◽  
Parallel Patterns ◽  
Selective Pressures ◽  
Sperm Flagellum ◽  
Ca2 Channels

AbstractSperm 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, CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the co-option of the polycystic kidney disease 2 (Dpkd2) Ca2+ 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.

scholarly journals Molecular Evolution of the Sex Peptide Network in Drosophila

2019 ◽  
Author(s):  
Meaghan K. McGeary ◽  
Geoffrey D. Findlay
Keyword(s):  
Sexual Selection ◽  
Molecular Evolution ◽  
Adaptive Evolution ◽  
Peptide Hormone ◽  
Sperm Length ◽  
Interacting Proteins ◽  
Reproductive Proteins ◽  
Functional Conservation ◽  
Network Function ◽  
Sex Peptide

AbstractSuccessful reproduction depends on interactions between numerous proteins beyond those involved directly in gamete fusion. While such reproductive proteins evolve in response to sexual selection pressures, how networks of interacting proteins arise and evolve as reproductive phenotypes change remains an open question. Here, we investigated the molecular evolution of the “sex peptide network” of Drosophila melanogaster, a functionally well-characterized reproductive protein network. In this species, the peptide hormone sex peptide (SP) and its interacting proteins cause major changes in female physiology and behavior after mating. In contrast, females of more distantly related Drosophila species do not respond to SP. In spite of these phenotypic differences, we detected orthologs of all network proteins across 22 diverse Drosophila species and found evidence that most orthologs likely function in reproduction throughout the genus. Within SP-responsive species, we detected the recurrent, adaptive evolution of several network proteins, consistent with sexual selection acting to continually refine network function. We also found some evidence for adaptive evolution of several proteins along two specific phylogenetic lineages that correspond with increased expression of the SP receptor in female reproductive tracts or increased sperm length, respectively. Finally, we used gene expression profiling to examine the likely degree of functional conservation of the paralogs of an SP network protein that arose via gene duplication. Our results suggest a dynamic history for the SP network in which network members arose before the onset of robust SP-mediated responses and then were shaped by both purifying and positive selection.

scholarly journals Parallel and non-parallel divergence within polymorphic populations of brook stickleback, Culaea inconstans (Actinopterygii: Gasterosteidae)

2021 ◽  
Author(s):  
Kaitlyn Willerth ◽  
Emily Franks ◽  
Jonathan A Mee
Keyword(s):  
Adaptive Evolution ◽  
Parallel Evolution ◽  
Threespine Stickleback ◽  
Ecological Consequences ◽  
Spine Morphology ◽  
Culaea Inconstans ◽  
Body Morphology ◽  
Selective Pressures ◽  
Brook Stickleback ◽  
Littoral Habitats

Studying parallel evolution allows us to draw conclusions about the repeatability of adaptive evolution. Whereas populations likely experience similar selective pressures in similar environments, it is not clear if this will always result in parallel divergence of ecologically relevant traits. Our study investigates the extent of parallelism associated with the evolution of pelvic spine reduction in brook stickleback populations. We find that populations with parallel divergence in pelvic spine morphology do not exhibit parallel divergence in head and body morphology but do exhibit parallel divergence in diet. In addition, we compare these patterns associated with pelvic reduction in brook stickleback to well-studied patterns of divergence between spined and unspined threespine stickleback. Whereas spine reduction is associated with littoral habitats and a benthic diet in threespine stickleback, spine reduction in brook stickleback is associated with a planktonic diet. Hence, we find that pelvic spine divergence is associated with largely non-parallel ecological consequences across species.

scholarly journals Assessing evidence for adaptive evolution in two hearing-related genes important for high-frequency hearing in echolocating mammals

2021 ◽  
Author(s):  
Hui Wang ◽  
Hanbo Zhao ◽  
Yujia Chu ◽  
Jiang Feng ◽  
Keping Sun
Keyword(s):  
Adaptive Evolution ◽  
Hair Cells ◽  
High Frequency ◽  
Phylogenetic Trees ◽  
Outer Hair Cells ◽  
Functional Domain ◽  
Coding Region ◽  
Selective Pressures ◽  
Wide Range ◽  
Different Parts

Abstract High-frequency hearing is particularly important for echolocating bats and toothed whales. Previously, studies of the hearing-related genes Prestin, KCNQ4, and TMC1 documented that adaptive evolution of high-frequency hearing has taken place in echolocating bats and toothed whales. In this study, we present two additional candidate hearing-related genes, Shh and SK2, that may also have contributed to the evolution of echolocation in mammals. Shh is a member of the vertebrate Hedgehog gene family and is required in the specification of the mammalian cochlea. SK2 is expressed in both inner and outer hair cells, and it plays an important role in the auditory system. The coding region sequences of Shh and SK2 were obtained from a wide range of mammals with and without echolocating ability. The topologies of phylogenetic trees constructed using Shh and SK2 were different; however, multiple molecular evolutionary analyses showed that those two genes experienced different selective pressures in echolocating bats and toothed whales compared to non-echolocating mammals. In addition, several nominally significant positively selected sites were detected in the non-functional domain of the SK2 gene, indicating that different selective pressures were acting on different parts of the SK2 gene. This study has expanded our knowledge of the adaptive evolution of high-frequency hearing in echolocating mammals.

Store-Operated Ca2+ Channels: Mechanism, Function, Pharmacology, and Therapeutic Targets

2021 ◽  
Vol 61 (1) ◽  
pp. 629-654
Author(s):  
Daniel Bakowski ◽  
Fraser Murray ◽  
Anant B. Parekh
Keyword(s):  
Channel Blockers ◽  
Channel Activity ◽  
Loss Of Function ◽  
Crac Channels ◽  
Crac Channel ◽  
Major Route ◽  
And Function ◽  
Therapeutic Perspective ◽  
Poor Efficacy ◽  
Ca2 Channels

Calcium (Ca2+) release–activated Ca2+ (CRAC) channels are a major route for Ca2+ entry in eukaryotic cells. These channels are store operated, opening when the endoplasmic reticulum (ER) is depleted of Ca2+, and are composed of the ER Ca2+ sensor protein STIM and the pore-forming plasma membrane subunit Orai. Recent years have heralded major strides in our understanding of the structure, gating, and function of the channels. Loss-of-function and gain-of-function mutants combined with RNAi knockdown strategies have revealed important roles for the channel in numerous human diseases, making the channel a clinically relevant target. Drugs targeting the channels generally lack specificity or exhibit poor efficacy in animal models. However, the landscape is changing, and CRAC channel blockers are now entering clinical trials. Here, we describe the key molecular and biological features of CRAC channels, consider various diseases associated with aberrant channel activity, and discuss targeting of the channels from a therapeutic perspective.

scholarly journals Hitchhiking and epistasis give rise to cohort dynamics in adapting populations

2017 ◽  
Vol 114 (31) ◽  
pp. 8330-8335 ◽  
Author(s):  
Sean W. Buskirk ◽  
Ryan Emily Peace ◽  
Gregory I. Lang
Keyword(s):  
Adaptive Evolution ◽  
Driving Force ◽  
Parallel Evolution ◽  
Low Frequency ◽  
Target Size ◽  
Driver Mutations ◽  
Beneficial Mutations ◽  
Large Target ◽  
Asexual Populations ◽  
Comprehensive Study

Beneficial mutations are the driving force of adaptive evolution. In asexual populations, the identification of beneficial alleles is confounded by the presence of genetically linked hitchhiker mutations. Parallel evolution experiments enable the recognition of common targets of selection; yet these targets are inherently enriched for genes of large target size and mutations of large effect. A comprehensive study of individual mutations is necessary to create a realistic picture of the evolutionarily significant spectrum of beneficial mutations. Here we use a bulk-segregant approach to identify the beneficial mutations across 11 lineages of experimentally evolved yeast populations. We report that nearly 80% of detected mutations have no discernible effects on fitness and less than 1% are deleterious. We determine the distribution of driver and hitchhiker mutations in 31 mutational cohorts, groups of mutations that arise synchronously from low frequency and track tightly with one another. Surprisingly, we find that one-third of cohorts lack identifiable driver mutations. In addition, we identify intracohort synergistic epistasis between alleles of hsl7 and kel1, which arose together in a low-frequency lineage.

scholarly journals Differential Interactions of Na+ Channel Toxins with T-type Ca2+ Channels

2008 ◽  
Vol 132 (1) ◽  
pp. 101-113 ◽  
Author(s):  
Hui Sun ◽  
Diego Varela ◽  
Denis Chartier ◽  
Peter C. Ruben ◽  
Stanley Nattel ◽  
...  
Keyword(s):  
Ventricular Myocytes ◽  
Low Voltage ◽  
Parallel Evolution ◽  
Na Channel ◽  
Patch Clamp Technique ◽  
Hek 293 ◽  
Inward Current ◽  
Whole Cell Patch Clamp ◽  
The Right ◽  
Ca2 Channels

Two types of voltage-dependent Ca2+ channels have been identified in heart: high (ICaL) and low (ICaT) voltage-activated Ca2+ channels. In guinea pig ventricular myocytes, low voltage–activated inward current consists of ICaT and a tetrodotoxin (TTX)-sensitive ICa component (ICa(TTX)). In this study, we reexamined the nature of low-threshold ICa in dog atrium, as well as whether it is affected by Na+ channel toxins. Ca2+ currents were recorded using the whole-cell patch clamp technique. In the absence of external Na+, a transient inward current activated near −50 mV, peaked at −30 mV, and reversed around +40 mV (HP = −90 mV). It was unaffected by 30 μM TTX or micromolar concentrations of external Na+, but was inhibited by 50 μM Ni2+ (by ∼90%) or 5 μM mibefradil (by ∼50%), consistent with the reported properties of ICaT. Addition of 30 μM TTX in the presence of Ni2+ increased the current approximately fourfold (41% of control), and shifted the dose–response curve of Ni2+ block to the right (IC50 from 7.6 to 30 μM). Saxitoxin (STX) at 1 μM abolished the current left in 50 μM Ni2+. In the absence of Ni2+, STX potently blocked ICaT (EC50 = 185 nM) and modestly reduced ICaL (EC50 = 1.6 μM). While TTX produced no direct effect on ICaT elicited by expression of hCaV3.1 and hCaV3.2 in HEK-293 cells, it significantly attenuated the block of this current by Ni2+ (IC50 increased to 550 μM Ni2+ for CaV3.1 and 15 μM Ni2+ for CaV3.2); in contrast, 30 μM TTX directly inhibited hCaV3.3-induced ICaT and the addition of 750 μM Ni2+ to the TTX-containing medium led to greater block of the current that was not significantly different than that produced by Ni2+ alone. 1 μM STX directly inhibited CaV3.1-, CaV3.2-, and CaV3.3-mediated ICaT but did not enhance the ability of Ni2+ to block these currents. These findings provide important new implications for our understanding of structure–function relationships of ICaT in heart, and further extend the hypothesis of a parallel evolution of Na+ and Ca2+ channels from an ancestor with common structural motifs.

scholarly journals Cystitis-Related Bladder Pain Involves ATP-Dependent HMGB1 Release from Macrophages and Its Downstream H2S/Cav3.2 Signaling in Mice

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1748 ◽  
Author(s):  
Shiori Hiramoto ◽  
Maho Tsubota ◽  
Kaoru Yamaguchi ◽  
Kyoko Okazaki ◽  
Aya Sakaegi ◽  
...  
Keyword(s):  
Atp Release ◽  
Raw264.7 Cells ◽  
Channel Activity ◽  
Nociceptive Behavior ◽  
P2x7 Receptors ◽  
Bladder Pain ◽  
T24 Cells ◽  
Ros Accumulation ◽  
Genetic Deletion ◽  
Ca2 Channels

Cystitis-related bladder pain involves RAGE activation by HMGB1, and increased Cav3.2 T-type Ca2+ channel activity by H2S, generated by upregulated cystathionine-γ-lyase (CSE) in mice treated with cyclophosphamide (CPA). We, thus, investigated possible crosstalk between the HMGB1/RAGE and CSE/H2S/Cav3.2 pathways in the bladder pain development. Bladder pain (nociceptive behavior/referred hyperalgesia) and immuno-reactive CSE expression in the bladder were determined in CPA-treated female mice. Cell signaling was analyzed in urothelial T24 and macrophage-like RAW264.7 cells. The CPA-induced bladder pain was abolished by pharmacological inhibition of T-type Ca2+ channels or CSE, and genetic deletion of Cav3.2. The CPA-induced CSE upregulation, as well as bladder pain was prevented by HMGB1 inactivation, inhibition of HMGB1 release from macrophages, antagonists of RAGE or P2X4/P2X7 receptors, and N-acetylcysteine, an antioxidant. Acrolein, a metabolite of CPA, triggered ATP release from T24 cells. Adenosine triphosphate (ATP) stimulated cell migration via P2X7/P2X4, and caused HMGB1 release via P2X7 in RAW264.7 cells, which was dependent on p38MAPK/NF-κB signaling and reactive oxygen species (ROS) accumulation. Together, our data suggest that CPA, once metabolized to acrolein, causes urothelial ATP-mediated, redox-dependent HMGB1 release from macrophages, which in turn causes RAGE-mediated CSE upregulation and subsequent H2S-targeted Cav3.2-dependent nociceptor excitation, resulting in bladder pain.

Epithelial Ca2+ channels sensitive to dihydropyridines and activated by hyperpolarizing voltages

1994 ◽  
Vol 267 (1) ◽  
pp. C157-C165 ◽  
Author(s):  
H. Matsunaga ◽  
B. A. Stanton ◽  
F. A. Gesek ◽  
P. A. Friedman
Keyword(s):  
Open Channel ◽  
Single Channel ◽  
Apical Membrane ◽  
Channel Activity ◽  
Channel Conductance ◽  
Single Channel Conductance ◽  
Nephron Segments ◽  
Convoluted Tubules ◽  
Ca2 Channels ◽  
In Cells

Parathyroid hormone (PTH) increases transcellular Ca2+ absorption in renal cortical thick ascending limbs and distal convoluted tubules (DCT). In cells isolated from these nephron segments, PTH increases Ca2+ uptake by a pathway that is sensitive to dihydropyridine-type agonists and antagonists (B. J. Bacskai and P. A. Friedman. Nature Lond. 347: 388-391, 1990). Patch-clamp techniques were used to identify Ca(2+)-permeable channels in DCT cells. Channel activity was detectable in cell-attached patches only in cells pretreated with PTH. Ca2+ channels exhibited prolonged open times (seconds), had a low single-channel conductance (2.1 pS), and open channel probability increased at hyperpolarizing voltages (-50 to -90 mV). Channel activity was sensitive to dihydropyridine-type compounds, nifedipine, and BAY K8644, as was Ca2+ uptake. However, Ca2+ entry was insensitive to verapamil or omega-conotoxin. These results demonstrate that these channels mediate PTH-stimulated apical membrane Ca2+ entry in DCT cells, which are the principal Ca(2+)-transporting cells of the kidney.

scholarly journals Solitary ecology as a phenomenon extending beyond insular systems: exaptive evolution in Anolis lizards

2019 ◽  
Vol 15 (5) ◽  
pp. 20190056 ◽  
Author(s):  
Julián A. Velasco ◽  
Steven Poe ◽  
Constantino González-Salazar ◽  
Oscar Flores-Villela
Keyword(s):  
Body Size ◽  
Adaptive Evolution ◽  
Environmental Filtering ◽  
Phenotypic Evolution ◽  
Phenotypic Differentiation ◽  
Evolutionary Transitions ◽  
Ecological Release ◽  
Selective Pressures ◽  
Island Species

The mechanisms driving phenotypic evolution have been of interest to biologists since Darwin. Ecological release—wherein adaptive evolution occurs following relaxation of constraining selective pressures—and environmental filtering—wherein exaptive traits allow colonization of a new area—have been studied in several insular cases. Anolis lizards, which may exist in solitude or sympatry with multiple congeners, are an excellent system for evaluating whether ecological release and environmental filtering are associated with phenotypic shifts across phylogenetic and geographical scales. Insular solitary Anolis exhibit phenotypic differentiation in body size and sexual size dimorphism—SSD—through exaptive and adaptive evolution, respectively. But, the generality of these effects has not yet been addressed. Here, we analyse the evolution of body size and SSD relative to sympatry in mainland Anolis . We found that mainland species co-occurring with few congeners exhibit uniform body size and greater SSD relative to other random mainland assemblages, consistent with the insular solitary pattern. The locations of evolutionary shifts for both traits do not coincide with evolutionary transitions to decreased levels of sympatry. These results are consistent with exaptive environmental filtering but not adaptive ecological release. Future studies should be conducted at local scales to evaluate the role of these factors in the evolution of solitary existence in mainland and island species.

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