Lu Ying

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  • 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
    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.