Zakon Harold H.

No Thumbnail Available
Last Name
Zakon
First Name
Harold H.
ORCID

Filters

2006 - 2009 2 2010 - 2015 4
3 3
6
Reset filters

Settings

Search Results

Now showing 1 - 6 of 6
  • Article
    The evolution of the four subunits of voltage-gated calcium channels : ancient roots, increasing complexity, and multiple losses
    (Oxford University Press, 2014-08-21) Moran, Yehu ; Zakon, Harold H.
    The alpha subunits of voltage-gated calcium channels (Cavs) are large transmembrane proteins responsible for crucial physiological processes in excitable cells. They are assisted by three auxiliary subunits that can modulate their electrical behavior. Little is known about the evolution and roles of the various subunits of Cavs in nonbilaterian animals and in nonanimal lineages. For this reason, we mapped the phyletic distribution of the four channel subunits and reconstructed their phylogeny. Although alpha subunits have deep evolutionary roots as ancient as the split between plants and opistokonths, beta subunits appeared in the last common ancestor of animals and their close-relatives choanoflagellates, gamma subunits are a bilaterian novelty and alpha2/delta subunits appeared in the lineage of Placozoa, Cnidaria, and Bilateria. We note that gene losses were extremely common in the evolution of Cavs, with noticeable losses in multiple clades of subfamilies and also of whole Cav families. As in vertebrates, but not protostomes, Cav channel genes duplicated in Cnidaria. We characterized by in situ hybridization the tissue distribution of alpha subunits in the sea anemone Nematostella vectensis, a nonbilaterian animal possessing all three Cav subfamilies common to Bilateria. We find that some of the alpha subunit subtypes exhibit distinct spatiotemporal expression patterns. Further, all six sea anemone alpha subunit subtypes are conserved in stony corals, which separated from anemones 500 MA. This unexpected conservation together with the expression patterns strongly supports the notion that these subtypes carry unique functional roles.
  • Article
    Sodium channel genes and the evolution of diversity in communication signals of electric fishes : convergent molecular evolution
    (National Academy of Sciences, 2006-02-27) Zakon, Harold H. ; Lu, Ying ; Zwickl, Derrick J. ; Hillis, David M.
    We investigated whether the evolution of electric organs and electric signal diversity in two independently evolved lineages of electric fishes was accompanied by convergent changes on the molecular level. We found that a sodium channel gene (Nav1.4a) that is expressed in muscle in nonelectric fishes has lost its expression in muscle and is expressed instead in the evolutionarily novel electric organ in both lineages of electric fishes. This gene appears to be evolving under positive selection in both lineages, facilitated by its restricted expression in the electric organ. This view is reinforced by the lack of evidence for selection on this gene in one electric species in which expression of this gene is retained in muscle. Amino acid replacements occur convergently in domains that influence channel inactivation, a key trait for shaping electric communication signals. Some amino acid replacements occur at or adjacent to sites at which disease-causing mutations have been mapped in human sodium channel genes, emphasizing that these replacements occur in functionally important domains. Selection appears to have acted on the final step in channel inactivation, but complementarily on the inactivation "ball" in one lineage, and its receptor site in the other lineage. Thus, changes in the expression and sequence of the same gene are associated with the independent evolution of signal complexity.
  • Preprint
    Adaptive evolution of voltage-gated sodium channels : the first 800 million years
    ( 2012-04) Zakon, Harold H.
    Voltage-gated Na+-permeable (Nav) channels form the basis for electrical excitability in animals. Nav channels evolved from Ca2+ channels and were present in the common ancestor of choanoflagellates and animals although this channel was likely permeable to both Na+ and Ca2+. Thus, like many other neuronal channels and receptors, Nav channels predated neurons. Invertebrates possess two Nav channels (Nav1, Nav2), whereas vertebrate Nav channels are of the Nav1 family. Approximately 500 MYA in early chordates Nav channels evolved a motif that allowed them to cluster at axon initial segments, 50MY later with the evolution of myelin, Nav channels “capitalized” on this property and clustered at nodes of Ranvier. The enhancement of conduction velocity along with the evolution of jaws likely made early gnathostomes fierce predators and the dominant vertebrates in the ocean. Later in vertebrate evolution, the Nav channel gene family expanded in parallel in tetrapods and teleosts (~9-10 genes in amniotes, 8 in teleosts). This expansion occurred during or after the late Devonian extinction when teleosts and tetrapods each diversified in their respective habitats and coincided with an increase in the number of telencephalic nuclei in both groups. The expansion of Nav channels may have allowed for more sophisticated neural computation and tailoring of Nav channel kinetics with potassium channel kinetics to enhance energy savings. Nav channels show adaptive sequence evolution for increasing diversity in communication signals (electric fish), in protection against lethal Nav channel toxins (snakes, newts, pufferfish, insects), and in specialized habitats (naked mole rats).
  • Preprint
    Expansion of voltage-dependent Na+ channel gene family in early tetrapods coincided with the emergence of terrestriality and increased brain complexity
    ( 2010-11-29) Zakon, Harold H. ; Jost, Manda C. ; Lu, Ying
    Mammals have 10 voltage-dependent sodium (Nav) channel genes. Nav channels are expressed in different cell types with different sub-cellular distributions and are critical for many aspects of neuronal processing. The last common ancestor of teleosts and tetrapods had four Nav channel genes presumably on four different chromosomes. In the lineage leading to mammals a series of tandem duplications on two of these chromosomes more than doubled the number of Nav channel genes. It is unknown when these duplications occurred, whether they occurred against a backdrop of duplication of flanking genes on their chromosomes, or as an expansion of ion channel genes in general. We estimated key dates of the Nav channel gene family expansion by phylogenetic analysis using teleost, elasmobranch, lungfish, amphibian, avian, lizard, and mammalian Nav channel sequences, as well as chromosomal synteny for tetrapod genes. We tested, and exclude, the null hypothesis that Nav channel genes reside in regions of chromosomes prone to duplication by demonstrating the lack of duplication or duplicate retention of surrounding genes. We also find no comparable expansion in other voltage dependent ion channel gene families of tetrapods following the teleost-tetrapod divergence. We posit a specific expansion of the Nav channel gene family in the Devonian and Carboniferous periods when tetrapods evolved, diversified, and invaded the terrestrial habitat. During this time the amniote forebrain evolved greater anatomical complexity and novel tactile sensory receptors appeared. The duplication of Nav channel genes allowed for greater regional specialization in Nav channel expression, variation in sub-cellular localization, and enhanced processing of somatosensory input.
  • Preprint
    Gene duplications and evolution of vertebrate voltage-gated sodium channels
    ( 2006-03-01) Novak, Alicia E. ; Jost, Manda C. ; Lu, Ying ; Taylor, Alison D. ; Zakon, Harold H. ; Ribera, Angeles B.
    Voltage-gated sodium channels underlie action potential generation in excitable tissue. To establish the evolutionary mechanisms that shaped the vertebrate sodium channel a-subunit (SCNA) gene family and their encoded Nav1 proteins, we identified all SCNA genes in several teleost species. Molecular cloning revealed that teleosts have eight SCNA genes, comparable to the number in another vertebrate lineage, mammals. Prior phylogenetic analyses had indicated that teleosts and tetrapods share four monophyletic groups of SCNA genes and that tandem duplications selectively expanded the number of genes in two of the four mammalian groups. However, the number of genes in each group varies between teleosts and tetrapods suggesting different evolutionary histories in the two vertebrate lineages. Our findings from phylogenetic analysis and chromosomal mapping of Danio rerio genes indicate that tandem duplications are an unlikely mechanism for generation of the extant teleost SCNA genes. Instead, analysis of other closely mapped genes in D. rerio supports the hypothesis that a whole genome duplication was involved in expansion of the SCNA gene family in teleosts. Interestingly, despite their different evolutionary histories, mRNA analyses demonstrated a conservation of expression patterns for SCNA orthologues in teleosts and tetrapods, suggesting functional conservation.
  • Article
    Unique patterns of transcript and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus)
    (BioMed Central, 2015-03-26) Traeger, Lindsay L. ; Volkening, Jeremy D. ; Moffett, Howell ; Gallant, Jason R. ; Chen, Po-Hao ; Novina, Carl D. ; Phillips, George N. ; Anand, Rene ; Wells, Gregg B. ; Pinch, Matthew ; Guth, Robert ; Unguez, Graciela A. ; Albert, James S. ; Zakon, Harold H. ; Sussman, Michael R. ; Samanta, Manoj P.
    With its unique ability to produce high-voltage electric discharges in excess of 600 volts, the South American strong voltage electric eel (Electrophorus electricus) has played an important role in the history of science. Remarkably little is understood about the molecular nature of its electric organs. We present an in-depth analysis of the genome of E. electricus, including the transcriptomes of eight mature tissues: brain, spinal cord, kidney, heart, skeletal muscle, Sachs’ electric organ, main electric organ, and Hunter’s electric organ. A gene set enrichment analysis based on gene ontology reveals enriched functions in all three electric organs related to transmembrane transport, androgen binding, and signaling. This study also represents the first analysis of miRNA in electric fish. It identified a number of miRNAs displaying electric organ-specific expression patterns, including one novel miRNA highly over-expressed in all three electric organs of E. electricus. All three electric organ tissues also express three conserved miRNAs that have been reported to inhibit muscle development in mammals, suggesting that miRNA-dependent regulation of gene expression might play an important role in specifying an electric organ identity from its muscle precursor. These miRNA data were supported using another complete miRNA profile from muscle and electric organ tissues of a second gymnotiform species. Our work on the E. electricus genome and eight tissue-specific gene expression profiles will greatly facilitate future research on determining the coding and regulatory sequences that specify the function, development, and evolution of electric organs. Moreover, these data and future studies will be informed by the first comprehensive analysis of miRNA expression in an electric fish presented here.