scholarly journals Epistasis is not a strong constraint on the recurrent evolution of toxin-resistant Na+,K+-ATPases among tetrapods

2021 ◽  
Author(s):  
Shabnam Mohammadi ◽  
Lu Yang ◽  
Santiago Herrera-Álvarez ◽  
María del Pilar Rodríguez-Ordoñez ◽  
Karen Zhang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Global Analysis ◽  
Sequence Divergence ◽  
Comparative Genomic ◽  
Protein Activity ◽  
Strong Constraint ◽  
Α Subunit ◽  
Genomic Studies ◽  
Key Sites ◽  
Diverse Groups

Comparative genomic studies reveal a global decline in rates of convergent amino acid substitution as a function of evolutionary distance. This pattern has been attributed to epistatic constraints on protein evolution, the idea being that mutations tend to confer the same fitness effects on more similar genetic backgrounds, so convergent substitutions are more likely to occur in closely related species. However, this hypothesis lacks experimental validation. We tested this model in the context of the recurrent evolution of resistance to cardiotonic steroids (CTS) across diverse groups of tetrapods, which occurs via specific amino acid substitutions to the α-subunit family of Na+,K+-ATPases (ATP1A). After identifying a series of recurrent substitutions at two key sites of ATP1A1 predicted to confer CTS resistance, we performed protein engineering experiments to test the functional consequences of introducing these substitutions onto divergent species backgrounds. While we find that substitutions at these sites can have substantial background-dependent effects on CTS resistance, we also find no evidence for background-dependent effects on protein activity. We further show that the magnitude of a substitution's effect on activity does not depend on the overall extent of ATP1A1 sequence divergence between species. More generally, a global analysis of substitution patterns across ATP1A orthologs and paralogs reveals that the probability of convergent substitution protein-wide is not predicted by sequence divergence. Together, these findings suggest that intramolecular epistasis is not an important constraint on the evolution of ATP1A CTS resistance in tetrapods.

Rh50 Glycoprotein Gene and Rhnull Disease: A Silent Splice Donor Is trans to a Gly279→Glu Missense Mutation in the Conserved Transmembrane Segment

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1776-1784 ◽  
Author(s):  
Cheng-Han Huang ◽  
Zhi Liu ◽  
Guangjie Cheng ◽  
Ying Chen
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Integral Membrane Protein ◽  
Gene Organization ◽  
Comparative Genomic ◽  
Transmembrane Segment ◽  
Protein Protein Interactions ◽  
Genomic Studies ◽  
American Society ◽  
Gt Element

Abstract Rhnull disease includes the amorph and regulator types that are thought to result from homozygous mutations at theRH30 and RH50 loci, respectively. Here we report an unusual regulator Rhnull where two G→A nucleotide (nt) transitions occurred in trans, targeting different regions of the two copies of Rh50 gene. The nt 836 G→A mutation was a missense change located in exon 6; it converted Gly into Glu at position 279, a central amino acid of the transmembrane segment 9 (TM9). While cDNA analysis showed expression of the 836A(Glu279) allele only, genomic studies showed the presence of both 836A(Glu279) and 836G(Gly279) alleles. A detailed analysis of gene organization led to the identification in the Rh50(836G) allele of a defective donor splice site, caused by a G→A mutation in the invariant GT element of intron 1. This is the first known example of such mutations that has apparently abolished the functional splicing of a pre-mRNA encoding a multipass integral membrane protein. With a silent phenotypic copy intrans, the negatively charged Glu279 residue may disrupt TM9 and impair the interaction of the missense protein with Rh30 polypeptides. To evaluate the significance of the mutation, we took a comparative genomic approach and identified Rh50 homologues in different species. We found that Gly279 is a conserved residue and its adjacent amino acid sequence is identical fromCaenorhabditis elegans to human. These findings provide new insight into the diversity of Rhnull disease and suggest that the C-terminal region of Rh50 may also participate in protein-protein interactions involving Rh complex formation. © 1998 by The American Society of Hematology.

scholarly journals Transcription Factors of the Alx Family: Evolutionarily Conserved Regulators of Deuterostome Skeletogenesis

2020 ◽  
Vol 11 ◽  
Author(s):  
Jian Ming Khor ◽  
Charles A. Ettensohn
Keyword(s):  
Transcription Factors ◽  
Gene Family ◽  
Current Knowledge ◽  
Comparative Genomic ◽  
Gene Duplications ◽  
Evolutionarily Conserved ◽  
Genomic Studies ◽  
Gene Regulatory ◽  
Paired Class ◽  
Diverse Groups

Members of the alx gene family encode transcription factors that contain a highly conserved Paired-class, DNA-binding homeodomain, and a C-terminal OAR/Aristaless domain. Phylogenetic and comparative genomic studies have revealed complex patterns of alx gene duplications during deuterostome evolution. Remarkably, alx genes have been implicated in skeletogenesis in both echinoderms and vertebrates. In this review, we provide an overview of current knowledge concerning alx genes in deuterostomes. We highlight their evolutionarily conserved role in skeletogenesis and draw parallels and distinctions between the skeletogenic gene regulatory circuitries of diverse groups within the superphylum.

Rh50 Glycoprotein Gene and Rhnull Disease: A Silent Splice Donor Is trans to a Gly279→Glu Missense Mutation in the Conserved Transmembrane Segment

Blood ◽  
1998 ◽  
Vol 92 (5) ◽  
pp. 1776-1784
Author(s):  
Cheng-Han Huang ◽  
Zhi Liu ◽  
Guangjie Cheng ◽  
Ying Chen
Keyword(s):  
Amino Acid ◽  
Protein Interactions ◽  
Integral Membrane Protein ◽  
Gene Organization ◽  
Comparative Genomic ◽  
Transmembrane Segment ◽  
Protein Protein Interactions ◽  
Genomic Studies ◽  
American Society ◽  
Gt Element

Rhnull disease includes the amorph and regulator types that are thought to result from homozygous mutations at theRH30 and RH50 loci, respectively. Here we report an unusual regulator Rhnull where two G→A nucleotide (nt) transitions occurred in trans, targeting different regions of the two copies of Rh50 gene. The nt 836 G→A mutation was a missense change located in exon 6; it converted Gly into Glu at position 279, a central amino acid of the transmembrane segment 9 (TM9). While cDNA analysis showed expression of the 836A(Glu279) allele only, genomic studies showed the presence of both 836A(Glu279) and 836G(Gly279) alleles. A detailed analysis of gene organization led to the identification in the Rh50(836G) allele of a defective donor splice site, caused by a G→A mutation in the invariant GT element of intron 1. This is the first known example of such mutations that has apparently abolished the functional splicing of a pre-mRNA encoding a multipass integral membrane protein. With a silent phenotypic copy intrans, the negatively charged Glu279 residue may disrupt TM9 and impair the interaction of the missense protein with Rh30 polypeptides. To evaluate the significance of the mutation, we took a comparative genomic approach and identified Rh50 homologues in different species. We found that Gly279 is a conserved residue and its adjacent amino acid sequence is identical fromCaenorhabditis elegans to human. These findings provide new insight into the diversity of Rhnull disease and suggest that the C-terminal region of Rh50 may also participate in protein-protein interactions involving Rh complex formation. © 1998 by The American Society of Hematology.

scholarly journals High-Density Genetic Map Construction and Identification of QTLs Controlling Leaf Abscission Trait in Poncirus trifoliata

2021 ◽  
Vol 22 (11) ◽  
pp. 5723
Author(s):  
Yuan-Yuan Xu ◽  
Sheng-Rui Liu ◽  
Zhi-Meng Gan ◽  
Ren-Fang Zeng ◽  
Jin-Zhi Zhang ◽  
...  
Keyword(s):  
Qtl Mapping ◽  
Linkage Map ◽  
Genetic Map ◽  
Expression Patterns ◽  
High Density ◽  
Poncirus Trifoliata ◽  
Leaf Abscission ◽  
Comparative Genomic ◽  
Map Comparison ◽  
Genomic Studies

A high-density genetic linkage map is essential for genetic and genomic studies including QTL mapping, genome assembly, and comparative genomic analysis. Here, we constructed a citrus high-density linkage map using SSR and SNP markers, which are evenly distributed across the citrus genome. The integrated linkage map contains 4163 markers with an average distance of 1.12 cM. The female and male linkage maps contain 1478 and 2976 markers with genetic lengths of 1093.90 cM and 1227.03 cM, respectively. Meanwhile, a genetic map comparison demonstrates that the linear order of common markers is highly conserved between the clementine mandarin and Poncirus trifoliata. Based on this high-density integrated citrus genetic map and two years of deciduous phenotypic data, two loci conferring leaf abscission phenotypic variation were detected on scaffold 1 (including 36 genes) and scaffold 8 (including 107 genes) using association analysis. Moreover, the expression patterns of 30 candidate genes were investigated under cold stress conditions because cold temperature is closely linked with the deciduous trait. The developed high-density genetic map will facilitate QTL mapping and genomic studies, and the localization of the leaf abscission deciduous trait will be valuable for understanding the mechanism of this deciduous trait and citrus breeding.

scholarly journals The Diversity and Evolution of Sex Chromosomes in Frogs

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 483
Author(s):  
Wen-Juan Ma ◽  
Paris Veltsos
Keyword(s):  
Sex Determination ◽  
Sex Chromosomes ◽  
Chromosome Evolution ◽  
Sex Chromosome ◽  
Comparative Genomic ◽  
Ancestral State ◽  
Heteromorphic Sex Chromosomes ◽  
Genomic Studies ◽  
Evolutionary Trajectories ◽  
Heterogametic Sex

Frogs are ideal organisms for studying sex chromosome evolution because of their diversity in sex chromosome differentiation and sex-determination systems. We review 222 anuran frogs, spanning ~220 Myr of divergence, with characterized sex chromosomes, and discuss their evolution, phylogenetic distribution and transitions between homomorphic and heteromorphic states, as well as between sex-determination systems. Most (~75%) anurans have homomorphic sex chromosomes, with XY systems being three times more common than ZW systems. Most remaining anurans (~25%) have heteromorphic sex chromosomes, with XY and ZW systems almost equally represented. There are Y-autosome fusions in 11 species, and no W-/Z-/X-autosome fusions are known. The phylogeny represents at least 19 transitions between sex-determination systems and at least 16 cases of independent evolution of heteromorphic sex chromosomes from homomorphy, the likely ancestral state. Five lineages mostly have heteromorphic sex chromosomes, which might have evolved due to demographic and sexual selection attributes of those lineages. Males do not recombine over most of their genome, regardless of which is the heterogametic sex. Nevertheless, telomere-restricted recombination between ZW chromosomes has evolved at least once. More comparative genomic studies are needed to understand the evolutionary trajectories of sex chromosomes among frog lineages, especially in the ZW systems.

scholarly journals The Amino Acid Sequence of the A Protein (α Subunit) of the Tryptophan Synthetase of Escherichia coli

1967 ◽  
Vol 242 (22) ◽  
pp. 5442-5446 ◽  
Author(s):  
John R. Guest ◽  
Gabriel R. Drapeau ◽  
Bruce C. Carlton ◽  
Charles Yanofsky
Keyword(s):  
Escherichia Coli ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Α Subunit ◽  
Tryptophan Synthetase

scholarly journals Hsp90 Binds and Regulates the Ligand-Inducible α Subunit of Eukaryotic Translation Initiation Factor Kinase Gcn2

1999 ◽  
Vol 19 (12) ◽  
pp. 8422-8432 ◽  
Author(s):  
Olivier Donzé ◽  
Didier Picard
Keyword(s):  
Amino Acid ◽  
Constitutive Expression ◽  
Amino Acid Starvation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Restrictive Temperature ◽  
Α Subunit ◽  
Macbecin I

ABSTRACT The protein kinase Gcn2 stimulates translation of the yeast transcription factor Gcn4 upon amino acid starvation. Using genetic and biochemical approaches, we show that Gcn2 is regulated by the molecular chaperone Hsp90 in budding yeast Saccharomyces cerevisiae. Specifically, we found that (i) several Hsp90 mutant strains exhibit constitutive expression of a GCN4-lacZ reporter plasmid; (ii) Gcn2 and Hsp90 form a complex in vitro as well as in vivo; (iii) the specific inhibitors of Hsp90, geldanamycin and macbecin I, enhance the association of Gcn2 with Hsp90 and inhibit its kinase activity in vitro; (iv) in vivo, macbecin I strongly reduces the levels of Gcn2; (v) in a strain expressing the temperature-sensitive Hsp90 mutant G170D, both the accumulation and activity of Gcn2 are abolished at the restrictive temperature; and (vi) the Hsp90 cochaperones Cdc37, Sti1, and Sba1 are required for the response to amino acid starvation. Taken together, these data identify Gcn2 as a novel target for Hsp90, which plays a crucial role for the maturation and regulation of Gcn2.

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