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1.
Pendrin and prestin both belong to a distinct anion transporter family called solute carrier protein 26A, or SLC26A. Pendrin (SLC26A4) is a chloride-iodide transporter that is found at the luminal membrane of follicular cells in the thyroid gland as well as in the endolymphatic duct and sac of the inner ear, whereas prestin (SLC26A5) is expressed in the plasma membrane of cochlear outer hair cells and functions as a unique voltage-dependent motor. We recently identified a motif that is critical for the motor function of prestin. We questioned whether it was possible to create a chimeric pendrin protein with motor capability by integrating this motility motif from prestin. The chimeric pendrin was constructed by substituting residues 160-179 in human pendrin with residues 156-169 from gerbil prestin. Non-linear capacitance and somatic motility, two hallmarks representing prestin function, were measured from chimeric pendrin-transfected human embryonic kidney 293 cells using the voltage clamp technique and photodiode-based displacement measurement system. We showed that this 14-amino acid substitution from prestin was able to confer pendrin with voltage-dependent motor capability despite the amino acid sequence disparity between pendrin and prestin. The molecular mechanism that facilitates motor function appeared to be the same as prestin because the motor activity depended on the concentration of intracellular chloride and was blocked by salicylate treatment. Radioisotope-labeled formate uptake measurements showed that the chimeric pendrin protein retained the capability to transport formate, suggesting that the gain of motor function was not at the expense of its inherent transport capability. Thus, the engineered pendrin was capable of both transporting anions and generating force. 相似文献
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Auditory detection is essential for survival and reproduction of vertebrates, yet the genetic changes underlying the evolution and diversity of hearing are poorly documented. Recent discoveries concerning prestin, which is responsible for cochlear amplification by electromotility, provide an opportunity to redress this situation. We identify prestin genes from the genomes of 14 vertebrates, including three fishes, one amphibian, one lizard, one bird, and eight mammals. An evolutionary analysis of these sequences and 34 previously known prestin genes reveals for the first time that this hearing gene was under positive selection in the most recent common ancestor (MRCA) of tetrapods. This discovery might document the genetic basis of enhanced high sound sensibility in tetrapods. An investigation of the adaptive gain and evolution of electromotility, an important evolutionary innovation for the highest hearing ability of mammals, detects evidence for positive selections on the MRCA of mammals, therians, and placentals, respectively. It is suggested that electromotility determined by prestin might initially appear in the MRCA of mammals, and its functional improvements might occur in the MRCA of therian and placental mammals. Our patch clamp experiments further support this hypothesis, revealing the functional divergence of voltage-dependent nonlinear capacitance of prestin from platypus, opossum, and gerbil. Moreover, structure-based cdocking analyses detect positively selected amino acids in the MRCA of placental mammals that are key residues in sulfate anion transport. This study provides new insights into the adaptation and functional diversity of hearing sensitivity in vertebrates by evolutionary and functional analysis of the hearing gene prestin. 相似文献
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The outer hair cell from Corti's organ possesses voltage-dependent intramembranous molecular motors evolved from the SLC26 anion transporter family. The motor, identified as prestin (SLC26a5), is responsible for electromotility of outer hair cells and mammalian cochlear amplification, a process that heightens our auditory responsiveness. Here, we describe experiments designed to evaluate the effects of anions on the motor's voltage-sensor charge movement, focusing on prestin's voltage-dependent Boltzmann characteristics. We find that the nature of the anion, including species, valence, and structure, regulates characteristics of the charge movement, signifying that anions play a more complicated role than simple voltage sensing in cochlear amplification. 相似文献
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Detro-Dassen S Schänzler M Lauks H Martin I zu Berstenhorst SM Nothmann D Torres-Salazar D Hidalgo P Schmalzing G Fahlke C 《The Journal of biological chemistry》2008,283(7):4177-4188
The SLC26 gene family encodes multifunctional transport proteins in numerous tissues and organs. Some paralogs function as anion exchangers, others as anion channels, and one, prestin (SLC26A5), represents a membrane-bound motor protein in outer hair cells of the inner ear. At present, little is known about the molecular basis of this functional diversity. We studied the subunit stoichiometry of one bacterial, one teleost, and two mammalian SLC26 isoforms expressed in Xenopus laevis oocytes or in mammalian cells using blue native PAGE and chemical cross-linking. All tested SLC26s are assembled as dimers composed of two identical subunits. Co-expression of two mutant prestins with distinct voltage-dependent capacitances results in motor proteins with novel electrical properties, indicating that the two subunits do not function independently. Our results indicate that an evolutionarily conserved dimeric quaternary structure represents the native and functional state of SLC26 transporters. 相似文献
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The plasma membrane of mammalian cochlear outer hair cells contains prestin, a unique motor protein. Prestin is the fifth member of the solute carrier protein 26A family. Orthologs of prestin are also found in the ear of non-mammalian vertebrates such as zebrafish and chicken. However, these orthologs are electrogenic anion exchangers/transporters with no motor function. Amphibian and reptilian lineages represent phylogenic branches in the evolution of tetrapods and subsequent amniotes. Comparison of the peptide sequences and functional properties of these prestin orthologs offer new insights into prestin evolution. With the recent availability of the lizard and frog genome sequences, we examined amino acid sequence and function of lizard and frog prestins to determine how they are functionally and structurally different from prestins of mammals and other non-mammals. Somatic motility, voltage-dependent nonlinear capacitance (NLC), the two hallmarks of prestin function, and transport capability were measured in transfected human embryonic kidney cells using voltage-clamp and radioisotope techniques. We demonstrated that while the transport capability of lizard and frog prestin was compatible to that of chicken prestin, the NLC of lizard prestin was more robust than that of chicken’s and was close to that of platypus. However, unlike platypus prestin which has acquired motor capability, lizard or frog prestin did not demonstrate motor capability. Lizard and frog prestins do not possess the same 11-amino-acid motif that is likely the structural adaptation for motor function in mammals. Thus, lizard and frog prestins appear to be functionally more advanced than that of chicken prestin, although motor capability is not yet acquired. 相似文献
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Jun-Ping Bai Simone Montoya Peter S. Aronson Joseph Santos-Sacchi Dhasakumar Navaratnam 《Biophysical journal》2009,96(8):3179-3186
The integral membrane protein prestin, a member of the SLC26 anion transporter family, is responsible for the voltage-driven electromotility of mammalian outer hair cells. It was argued that the evolution of prestin's motor function required a loss of the protein's transport capabilities. Instead, it was proposed that prestin manages only an abortive hemicycle that results in the trapped anion acting as a voltage sensor, to generate the motor's signature gating charge movement or nonlinear capacitance. We demonstrate, using classical radioactive anion ([14C]formate and [14C]oxalate) uptake studies, that in contrast to previous observations, prestin is able to transport anions. The prestin-dependent uptake of both these anions was twofold that of cells transfected with vector alone, and comparable to SLC26a6, prestin's closest phylogenetic relative. Furthermore, we identify a potential chloride-binding site in which the mutations of two residues (P328A and L326A) preserve nonlinear capacitance, yet negate anion transport. Finally, we distinguish 12 charged residues out of 22, residing within prestin's transmembrane regions, that contribute to unitary charge movement, i.e., voltage sensing. These data redefine our mechanistic concept of prestin. 相似文献
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Hoppe R Lambert TD Samollow PB Breer H Strotmann J 《Journal of molecular evolution》2006,62(4):460-472
Genes encoding the olfactory receptors of the “OR37” subfamily of the mouse are characterized by special features including
a clustered expression pattern, assembly in two distinct gene clusters, and highly conserved putative promoter motifs. Mining
the rat and dog databases revealed that these two species possess highly conserved clusters of OR37 genes at two syntenic
genomic loci. In a prototherian mammal, the platypus (Ornithorhynchus anatinus), none of the characteristic OR37 genes were found. Examination of a metatherian mammal, the gray short-tailed opossum (Monodelphis domestica) revealed seven canonical OR37 genes, all phylogenetically related to cluster II genes and also organized similar to cluster
II of eutherian species. In addition, their 5′ upstream regions comprised sequence motifs related to the putative regulatory
sequences of cluster II genes. Typical cluster I OR37 genes were identified only in the eutherian mammals examined, including
the evolutionary ancient anteater, wherein OR37 genes related to both clusters were present. Together, these results reveal
novel information concerning the phylogenetic origin and important evolutionary steps of the mammalian-specific OR37 olfactory
receptor family.
[Reviewing Editor: Dr. Lauren Ancel Meyers]
Reiner Hoppe and Thomas D. Lambert are contributed equally to this work. 相似文献
12.
While the the role of the homeodomain in HOX function has been evaluated extensively, little attention has been given to
the non-homeodomain portions of the HOX proteins. To investigate the evolution of the HOXA13 protein and to identify conserved
residues in the N-terminal region of the protein with potential functional significance, N-terminal Hoxa13 coding sequences were PCR-amplified from fish, amphibian, reptile, chicken, and marsupial and eutherian mammal genomic DNA.
Compared with fish HOXA13, the mammalian protein has increased in size by 35% primarily owing to the accumulation of alanine
repeats and flanking segments rich in proline, glycine, or serine within the first 215 amino acids. Certain residues and amino
acid motifs were strongly conserved, and several HOXA13 N-terminal domains were also shared in the paralogous HOXB13 and HOXD13
genes; however, other conserved regions appear to be unique to HOXA13. Two domains highly conserved in HOXA13 orthologs are
shared with Drosophila AbdB and other vertebrate AbdB-like proteins. Marsupial and eutherian mammalian HOXA13 proteins have three large homopolymeric
alanine repeats of 14, 12, and 17–18 residues that are absent in reptiles, birds, and fish. Thus, the repeats arose after
the divergence of reptiles from the lineage that would give rise to the mammals. In contrast, other short homopolymeric alanine
repeats in mammalian HOXA13 have remained virtually the same length, suggesting that forces driving or limiting repeat expansion
are context dependent. Consecutive stretches of identical third-base usage in alanine codons within the large repeats were
found, supporting replication slippage as a mechanism for their generation. However, numerous species-specific base substitutions
affecting third-base alanine repeat codon positions were observed, particularly in the largest repeat. Therefore, if the large
alanine repeats were present prior to eutherian mammal development as is suggested by the opossum data, then a dynamic process
of recurring replication slippage and point mutation within alanine repeat codons must be considered to reconcile these observations.
This model might also explain why the alanine repeats are flanked by proline, serine, and glycine-rich sequences, and it reveals
a biological mechanism that promotes increases in protein size and, potentially, acquisition of new functions.
Received: 8 June 1999 / Accepted: 23 September 1999 相似文献
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Neil J. Gemmell Axel Janke Patrick S. Western Jaclyn M. Watson Svante Pääbo Jennifer A. Marshall Graves 《Journal of molecular evolution》1994,39(2):200-205
The vertebrate mitochondrial genome is highly conserved in size and gene content. Among the chordates there appears to be one basic gene arrangement, but rearrangements in the mitochondrial gene order of the avian lineages have indicated that the mitochondrial genome may be more variable than once thought. Different gene orders in marsupials and eutherian mammals leave the ancestral mammalian order in some doubt. We have investigated the mitochondrial gene order in the platypus (Ornithorhynchus anatinus), a representative of the third major group of mammals, to determine which mitochondrial gene arrangement is ancestral in mammals. We have found that the platypus mtDNA conforms to the basic chordate gene arrangement, common to fish, amphibians, and eutherian mammals, indicating that this arrangement was the original mammalian arrangement, and that the unusual rearrangements observed in the avians and marsupials are probably lineage-specific.
Correspondence to: N.J. Gemmell 相似文献
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Several clones containing DMP1 cDNA were isolated from a caiman tooth library by screening with a platypus DMP1 probe. The caiman DMP1 shows little amino acid sequence similarity to mammalian DMP1s for much of its length. A few highly conserved regions can, however, be identified that correspond to the slowly evolving parts of the corresponding mammalian genes. Southern blot analysis using probes comprising either conserved regions or longer segments of the gene indicates that only a single DMP1 locus exists. In coding regions, exon-intron boundaries and reading frames are shared by caiman and mammalian genes with the exception of exons 1 and 5, which are longer in the caiman. The repetitive sequence of the last exon is shared by mammals and caiman as are the high Ser content and acidity due to a high proportion of Asp and Glu residues. The conserved mammalian cell-attachment signal Arg-Gly-Asp is absent in the caiman DMP1. In contrast to the amelogenin gene, the DMP1 gene appears to evolve rapidly in vertebrates. 相似文献
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Ma Din-Pow Andrey Zharkikh Dan Graur John L. VandeBerg Wen-Hsiung Lie 《Journal of molecular evolution》1993,36(4):327-334
Summary We have sequenced the mitochondrial cytochrome b gene from the guinea pig, the African porcupine, and a South American opossum. A phylogenetic analysis, which includes 22 eutherian and four other vertebrate cytochrome b sequences, indicates that the guinea pig and the porcupine constitute a natural clade (Hystricomorpha) that is not a sister group to the clade of mice and rats (Myomorpha). Therefore, the hypothesis that the Rodentia is paraphyletic receives additional support. The artiodactyls, the perissodactyls, and the cetaceans form a group that is separated from the primates and the rodents. The 26 sequences are used to study the structure/function relationships in cytochrome b, whose function is electron transport. Most of the amino acid residues involved in the two reaction centers are well conserved in evolution. The four histidines that are believed to ligate the two hemes are invariant among the 26 sequences, but their nearby residues are not well conserved in evolution. The eight transmembrane domains represent some of the most divergent regions in the cytochrome b sequence. The rate of nonsynonymous substitution is considerably faster in the human and elephant lineages than in other eutherian lineages; the faster rate might be due to coevolution between cytochrome b and cytochrome c.
Offprint requests to: W.-H. Li 相似文献
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Mammalian ALDH3 genes (ALDH3A1, ALDH3A2, ALDH3B1 and ALDH3B2) encode enzymes of peroxidic and fatty aldehyde metabolism. ALDH3A1 also plays a major role in anterior eye tissue UV-filtration. BLAT and BLAST analyses were undertaken of several vertebrate genomes using rat, chicken and zebrafish ALDH3-like amino acid sequences. Predicted vertebrate ALDH3 sequences and structures were highly conserved, including residues involved in catalysis, coenzyme binding and enzyme structure as reported by Liu et al. [27] for rat ALDH3A1. Phylogeny studies of human, rat, opossum, platypus, chicken, xenopus and zebrafish ALDH3-like sequences supported three hypotheses: (1) the mammalian ALDH3A1 gene was generated by a tandem duplication event of an ancestral vertebrate ALDH3A2 gene; (2) multiple mammalian and chicken ALDH3B-like genes were generated by tandem duplication events within genomes of related species; and (3) vertebrate ALDH3A and ALDH3B genes were generated prior to the appearance of bony fish more than 500 million years ago. 相似文献
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Somatic electromotility in cochlear outer hair cells, as the basis for cochlear amplification, is a mammalian novelty and it is largely dependent upon rapid cell length changes proposed to be mediated by the motor-protein prestin, a member of the solute carrier anion-transport family 26. Thus, one might predict that prestin has specifically evolved in mammals to support this unique mammalian adaptation. Using codon-based likelihood models we found evidences for positive selection in the motor-protein prestin only in the mammalian lineage, supporting the hypothesis that lineage-specific adaptation-driven molecular changes endowed prestin with the ability to mediate somatic electromotility. Moreover, signatures of positive selection were found on the alpha10, but not the alpha9, nicotinic cholinergic receptor subunits. An alpha9alpha10-containing nicotinic cholinergic receptor mediates inhibitory olivocochlear efferent effects on hair cells across vertebrates. Our results suggest that evolution-driven modifications of the alpha10 subunit probably allowed the alpha9alpha10 heteromeric receptor to serve a differential function in the mammalian cochlea. Thus, we describe for the first time at the molecular level signatures of adaptive evolution in two outer hair cell proteins only in the lineage leading to mammals. This finding is most likely related with the roles these proteins play in somatic electromotility and/or its fine tuning. 相似文献
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Mapping of five new putative anion transporter genes in human and characterization of SLC26A6, a candidate gene for pancreatic anion exchanger 总被引:11,自引:0,他引:11
A second distinct family of anion transporters, in addition to the classical SLC4 (or AE) family, has recently been delineated. Members of the SLC26 family are structurally well conserved and can mediate the electroneutral exchange of Cl(-) for HCO(-)(3) across the plasma membrane of mammalian cells like members of the SLC4 family. Three human transporter proteins have been functionally characterized: SLC26A2 (DTDST), SLC26A3 (CLD or DRA), and SLC26A4 (PDS) can transport with different specificities the chloride, iodine, bicarbonate, oxalate, and hydroxyl anions, whereas SLC26A5 (prestin) was suggested to act as the motor protein of the cochlear outer hair cell. We report the expansion of the SLC26 family with five new members in chromosomes 3, 6, 8, 12, and 17 and mapping of SLC26A1 to 4p16.3. We have characterized one of them, SLC26A6, in more detail. It maps to chromosome 3p21.3, encodes a predicted 738-amino-acid transmembrane protein, and is most abundantly expressed in the kidney and pancreas. Pancreatic ductal cell lines Capan-1 and Capan-2 express SLC26A6, and immunohistochemistry localizes SLC26A6 protein to the apical surface of pancreatic ductal cells, suggesting it as a candidate for a luminal anion exchanger. The functional characterization of the novel members of this tissue-specific gene family may provide new insights into anion transport physiology in different parts of the body. 相似文献
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Andrew J Pask Anthony T Papenfuss Eleanor I Ager Kaighin A McColl Terence P Speed Marilyn B Renfree 《Genome biology》2009,10(1):R1-8
Background
Genomic imprinting is an epigenetic phenomenon that results in monoallelic gene expression. Many hypotheses have been advanced to explain why genomic imprinting evolved in mammals, but few have examined how it arose. The host defence hypothesis suggests that imprinting evolved from existing mechanisms within the cell that act to silence foreign DNA elements that insert into the genome. However, the changes to the mammalian genome that accompanied the evolution of imprinting have been hard to define due to the absence of large scale genomic resources between all extant classes. The recent release of the platypus genome has provided the first opportunity to perform comparisons between prototherian (monotreme; which appear to lack imprinting) and therian (marsupial and eutherian; which have imprinting) mammals. 相似文献20.
The mammalian centromere-associated protein B (CENP-B) shares significant sequence similarity with 3 proteins in fission yeast (Abp1, Cbh1, and Cbh2) that also bind centromeres and have essential function for chromosome segregation and centromeric heterochromatin formation. Each of these proteins displays extensive sequence similarity with pogo-like transposases, which have been previously identified in the genomes of various insects and vertebrates, in the protozoan Entamoeba and in plants. Based on this distribution, it has been proposed that the mammalian and fission yeast centromeric proteins are derived from "domesticated" pogo-like transposons. Here we took advantage of the vast amount of sequence information that has become recently available for a wide range of fungal and animal species to investigate the origin of the mammalian CENP-B and yeast CENP-B-like genes. A highly conserved ortholog of CENP-B was detected in 31 species of mammals, including opossum and platypus, but was absent from all nonmammalian species represented in the databases. Similarly, no ortholog of the fission yeast centromeric proteins was identified in any of the various fungal genomes currently available. In contrast, we discovered a plethora of novel pogo-like transposons in diverse invertebrates and vertebrates and in several filamentous fungi. Phylogenetic analysis revealed that the mammalian and fission yeast CENP-B proteins fall into 2 distinct monophyletic clades, each of which includes a different set of pogo-like transposons. These results are most parsimoniously explained by independent domestication events of pogo-like transposases into centromeric proteins in the mammalian and fission yeast lineages, a case of "convergent domestication." These findings highlight the propensity of transposases to give rise to new host proteins and the potential of transposons as sources of genetic innovation. 相似文献