Limits...
The Nature, Extent, and Consequences of Genetic Variation in the opa Repeats of Notch in Drosophila.

Rice C, Beekman D, Liu L, Erives A - G3 (Bethesda) (2015)

Bottom Line: We introgressed these opa variant alleles into common backgrounds and measured the frequency of Notch-type phenotypes.Homozygotes for the short and long opa alleles have defects in embryonic survival and sensory bristle organ patterning, and sometimes show wing notching.Our results demonstrate the existence of potent pQ variants of Notch and the need for long read genotyping of key repeat variables underlying gene regulatory networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Iowa, Iowa City, Iowa 52242-1324.

No MeSH data available.


Related in: MedlinePlus

The cleaved Notch intracellular domain (NICD) is characterized by a polyglutamine (pQ) tract configuration that is unique to each Drosophila species. (A) Shown is the 939-residue-long polypeptide sequence for NICD from D. melanogaster. Residues that tend to be secondary structure breakers are highlighted in cyan (p, g, s, D, N, and H), with the smaller amino acids shown in lowercase lettering. Glutamines (Qs) are shown in red. The seven ankyrin repeats are shown in alternating bold and dotted underlining. Two nuclear localization sequences, NLS1 (KRQR) and NLS2 (KKAK), are indicated with double wavy underlining. The Nedd4 ubiquitination site (ppsY) is also indicated in light wavy underlining. (B) Much of the NICD is disordered, as demonstrated by this plot of long disorder tendency based on pairwise energy content (IUPred) (Dosztányi et al. 2005a,b). The ankyrin (ANK) repeats (residue positions 137–384) and the pQ tracts (Q13HQ17 at residue positions 774–804) are notable for having the least and most disorder tendencies, respectively (highlighted in yellow). (C) The opa-encoded pQ repeats of the melanogaster subgroup are characterized by two adjacent pQ tracts separated by a single conserved histidine. While the surrounding amino acids are conserved, each species features a unique pQ configuration characterized by the length of the pQ tracts on either side of the histidine. The assembly for Drosophila mauritiana indicates a unique position for the His residue even though the entire opa repeat sequence is still uncertain (Garrigan et al. 2012). In this study, we refer to different Notch opa configurations by appending the length suffix to the word “opa.” We add an additional index when more than one configuration exists for a given length as distinguished by the position of the single histidine (e.g., opa25-secvs.opa25-yak, or opa33avs.opa33b in D. melanogaster). Unless a species is indicated (e.g., opa26-sim), all opa designations refer to alleles from D. melanogaster.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4632060&req=5

fig1: The cleaved Notch intracellular domain (NICD) is characterized by a polyglutamine (pQ) tract configuration that is unique to each Drosophila species. (A) Shown is the 939-residue-long polypeptide sequence for NICD from D. melanogaster. Residues that tend to be secondary structure breakers are highlighted in cyan (p, g, s, D, N, and H), with the smaller amino acids shown in lowercase lettering. Glutamines (Qs) are shown in red. The seven ankyrin repeats are shown in alternating bold and dotted underlining. Two nuclear localization sequences, NLS1 (KRQR) and NLS2 (KKAK), are indicated with double wavy underlining. The Nedd4 ubiquitination site (ppsY) is also indicated in light wavy underlining. (B) Much of the NICD is disordered, as demonstrated by this plot of long disorder tendency based on pairwise energy content (IUPred) (Dosztányi et al. 2005a,b). The ankyrin (ANK) repeats (residue positions 137–384) and the pQ tracts (Q13HQ17 at residue positions 774–804) are notable for having the least and most disorder tendencies, respectively (highlighted in yellow). (C) The opa-encoded pQ repeats of the melanogaster subgroup are characterized by two adjacent pQ tracts separated by a single conserved histidine. While the surrounding amino acids are conserved, each species features a unique pQ configuration characterized by the length of the pQ tracts on either side of the histidine. The assembly for Drosophila mauritiana indicates a unique position for the His residue even though the entire opa repeat sequence is still uncertain (Garrigan et al. 2012). In this study, we refer to different Notch opa configurations by appending the length suffix to the word “opa.” We add an additional index when more than one configuration exists for a given length as distinguished by the position of the single histidine (e.g., opa25-secvs.opa25-yak, or opa33avs.opa33b in D. melanogaster). Unless a species is indicated (e.g., opa26-sim), all opa designations refer to alleles from D. melanogaster.

Mentions: The opa nucleotide repeats are located in the eighth exon of Notch (N) and encode two polyglutamine (pQ) tracts separated by a single histidine (H) (Figure 1). This pQ-H-pQ sequence is part of the Notch intracellular domain (NICD), which is translocated into the nucleus upon cleavage (Figure 1A). These pQ tracts are intrinsically disordered and surrounded by many other similar peaks of disorder (Figure 1B). While the NICD pQ tracts are immediately flanked by conserved amino acid sequence, we find evidence of multiple opa repeat configurations that are unique to the Notch gene of D. melanogaster (Figure 1C). To better relate our phenotypic results from studying variant Notch opa alleles, we introduce a simple nomenclature for the different opa-encoded pQ configurations.


The Nature, Extent, and Consequences of Genetic Variation in the opa Repeats of Notch in Drosophila.

Rice C, Beekman D, Liu L, Erives A - G3 (Bethesda) (2015)

The cleaved Notch intracellular domain (NICD) is characterized by a polyglutamine (pQ) tract configuration that is unique to each Drosophila species. (A) Shown is the 939-residue-long polypeptide sequence for NICD from D. melanogaster. Residues that tend to be secondary structure breakers are highlighted in cyan (p, g, s, D, N, and H), with the smaller amino acids shown in lowercase lettering. Glutamines (Qs) are shown in red. The seven ankyrin repeats are shown in alternating bold and dotted underlining. Two nuclear localization sequences, NLS1 (KRQR) and NLS2 (KKAK), are indicated with double wavy underlining. The Nedd4 ubiquitination site (ppsY) is also indicated in light wavy underlining. (B) Much of the NICD is disordered, as demonstrated by this plot of long disorder tendency based on pairwise energy content (IUPred) (Dosztányi et al. 2005a,b). The ankyrin (ANK) repeats (residue positions 137–384) and the pQ tracts (Q13HQ17 at residue positions 774–804) are notable for having the least and most disorder tendencies, respectively (highlighted in yellow). (C) The opa-encoded pQ repeats of the melanogaster subgroup are characterized by two adjacent pQ tracts separated by a single conserved histidine. While the surrounding amino acids are conserved, each species features a unique pQ configuration characterized by the length of the pQ tracts on either side of the histidine. The assembly for Drosophila mauritiana indicates a unique position for the His residue even though the entire opa repeat sequence is still uncertain (Garrigan et al. 2012). In this study, we refer to different Notch opa configurations by appending the length suffix to the word “opa.” We add an additional index when more than one configuration exists for a given length as distinguished by the position of the single histidine (e.g., opa25-secvs.opa25-yak, or opa33avs.opa33b in D. melanogaster). Unless a species is indicated (e.g., opa26-sim), all opa designations refer to alleles from D. melanogaster.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4632060&req=5

fig1: The cleaved Notch intracellular domain (NICD) is characterized by a polyglutamine (pQ) tract configuration that is unique to each Drosophila species. (A) Shown is the 939-residue-long polypeptide sequence for NICD from D. melanogaster. Residues that tend to be secondary structure breakers are highlighted in cyan (p, g, s, D, N, and H), with the smaller amino acids shown in lowercase lettering. Glutamines (Qs) are shown in red. The seven ankyrin repeats are shown in alternating bold and dotted underlining. Two nuclear localization sequences, NLS1 (KRQR) and NLS2 (KKAK), are indicated with double wavy underlining. The Nedd4 ubiquitination site (ppsY) is also indicated in light wavy underlining. (B) Much of the NICD is disordered, as demonstrated by this plot of long disorder tendency based on pairwise energy content (IUPred) (Dosztányi et al. 2005a,b). The ankyrin (ANK) repeats (residue positions 137–384) and the pQ tracts (Q13HQ17 at residue positions 774–804) are notable for having the least and most disorder tendencies, respectively (highlighted in yellow). (C) The opa-encoded pQ repeats of the melanogaster subgroup are characterized by two adjacent pQ tracts separated by a single conserved histidine. While the surrounding amino acids are conserved, each species features a unique pQ configuration characterized by the length of the pQ tracts on either side of the histidine. The assembly for Drosophila mauritiana indicates a unique position for the His residue even though the entire opa repeat sequence is still uncertain (Garrigan et al. 2012). In this study, we refer to different Notch opa configurations by appending the length suffix to the word “opa.” We add an additional index when more than one configuration exists for a given length as distinguished by the position of the single histidine (e.g., opa25-secvs.opa25-yak, or opa33avs.opa33b in D. melanogaster). Unless a species is indicated (e.g., opa26-sim), all opa designations refer to alleles from D. melanogaster.
Mentions: The opa nucleotide repeats are located in the eighth exon of Notch (N) and encode two polyglutamine (pQ) tracts separated by a single histidine (H) (Figure 1). This pQ-H-pQ sequence is part of the Notch intracellular domain (NICD), which is translocated into the nucleus upon cleavage (Figure 1A). These pQ tracts are intrinsically disordered and surrounded by many other similar peaks of disorder (Figure 1B). While the NICD pQ tracts are immediately flanked by conserved amino acid sequence, we find evidence of multiple opa repeat configurations that are unique to the Notch gene of D. melanogaster (Figure 1C). To better relate our phenotypic results from studying variant Notch opa alleles, we introduce a simple nomenclature for the different opa-encoded pQ configurations.

Bottom Line: We introgressed these opa variant alleles into common backgrounds and measured the frequency of Notch-type phenotypes.Homozygotes for the short and long opa alleles have defects in embryonic survival and sensory bristle organ patterning, and sometimes show wing notching.Our results demonstrate the existence of potent pQ variants of Notch and the need for long read genotyping of key repeat variables underlying gene regulatory networks.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, University of Iowa, Iowa City, Iowa 52242-1324.

No MeSH data available.


Related in: MedlinePlus