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Dynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers.

Crocker J, Potter N, Erives A - Nat Commun (2010)

Bottom Line: However, NEEs also possess dense clusters of variant Dl sites.Here, we show that these increasingly variant sites are eclipsed relic elements, which were superseded by more recently evolved threshold encodings.Given the divergence in egg size during Drosophila lineage evolution, the observed characteristic clusters of divergent sites indicate a history of frequent selection for changes in threshold responses to the Dl morphogen gradient and confirm the NEE structure/function model.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA.

ABSTRACT
Concentration gradients of morphogenic proteins pattern the embryonic axes of Drosophila by activating different genes at different concentrations. The neurogenic ectoderm enhancers (NEEs) activate different genes at different threshold levels of the Dorsal (Dl) morphogen, which patterns the dorsal/ventral axis. NEEs share a unique arrangement of highly constrained DNA-binding sites for Dl, Twist (Twi), Snail (Sna) and Suppressor of Hairless (Su(H)), and encode the threshold variable in the precise length of DNA that separates one well-defined Dl element from a Twi element. However, NEEs also possess dense clusters of variant Dl sites. Here, we show that these increasingly variant sites are eclipsed relic elements, which were superseded by more recently evolved threshold encodings. Given the divergence in egg size during Drosophila lineage evolution, the observed characteristic clusters of divergent sites indicate a history of frequent selection for changes in threshold responses to the Dl morphogen gradient and confirm the NEE structure/function model.

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Su(H)-binding sites are exapted from Dl relic sequences in mature NEEs.(a) Alignment of the lineage-specific consensi for Dα shows that the portion overlapping the Su(H)-binding site is the least divergent (purple), whereas the second half-site is degenerate relative to other lineages (black struck-out letters). Also shown are the wild-type and mutated sequences of this site tested in the rho NEE from D. melanogaster (D. mel.). (b, c) Typical lacZ expression patterns driven by rho NEE reporters containing the full SUH/Dα site (b) or the knocked out (KO) Su(H) site (c).
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f6: Su(H)-binding sites are exapted from Dl relic sequences in mature NEEs.(a) Alignment of the lineage-specific consensi for Dα shows that the portion overlapping the Su(H)-binding site is the least divergent (purple), whereas the second half-site is degenerate relative to other lineages (black struck-out letters). Also shown are the wild-type and mutated sequences of this site tested in the rho NEE from D. melanogaster (D. mel.). (b, c) Typical lacZ expression patterns driven by rho NEE reporters containing the full SUH/Dα site (b) or the knocked out (KO) Su(H) site (c).

Mentions: A high frequency of threshold replacement suggests that the specialized SUH/Dα site may originate as a Dβ relic element that is exapted into a Su(H)-binding site. We therefore compared the Dα and Dβ consensi motifs across all five divergent Drosophila lineages for which we functionally tested NEEs (Fig. 6a). We find that the first half of the Dα motif, which overlaps the Su(H)-binding motif, is conserved whereas the second half is increasingly degenerate relative to the inferred ancestral Dα motif, which resembles a Dβ motif itself (compare Su(H) with Dα motifs in Fig. 6a).


Dynamic evolution of precise regulatory encodings creates the clustered site signature of enhancers.

Crocker J, Potter N, Erives A - Nat Commun (2010)

Su(H)-binding sites are exapted from Dl relic sequences in mature NEEs.(a) Alignment of the lineage-specific consensi for Dα shows that the portion overlapping the Su(H)-binding site is the least divergent (purple), whereas the second half-site is degenerate relative to other lineages (black struck-out letters). Also shown are the wild-type and mutated sequences of this site tested in the rho NEE from D. melanogaster (D. mel.). (b, c) Typical lacZ expression patterns driven by rho NEE reporters containing the full SUH/Dα site (b) or the knocked out (KO) Su(H) site (c).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2963808&req=5

f6: Su(H)-binding sites are exapted from Dl relic sequences in mature NEEs.(a) Alignment of the lineage-specific consensi for Dα shows that the portion overlapping the Su(H)-binding site is the least divergent (purple), whereas the second half-site is degenerate relative to other lineages (black struck-out letters). Also shown are the wild-type and mutated sequences of this site tested in the rho NEE from D. melanogaster (D. mel.). (b, c) Typical lacZ expression patterns driven by rho NEE reporters containing the full SUH/Dα site (b) or the knocked out (KO) Su(H) site (c).
Mentions: A high frequency of threshold replacement suggests that the specialized SUH/Dα site may originate as a Dβ relic element that is exapted into a Su(H)-binding site. We therefore compared the Dα and Dβ consensi motifs across all five divergent Drosophila lineages for which we functionally tested NEEs (Fig. 6a). We find that the first half of the Dα motif, which overlaps the Su(H)-binding motif, is conserved whereas the second half is increasingly degenerate relative to the inferred ancestral Dα motif, which resembles a Dβ motif itself (compare Su(H) with Dα motifs in Fig. 6a).

Bottom Line: However, NEEs also possess dense clusters of variant Dl sites.Here, we show that these increasingly variant sites are eclipsed relic elements, which were superseded by more recently evolved threshold encodings.Given the divergence in egg size during Drosophila lineage evolution, the observed characteristic clusters of divergent sites indicate a history of frequent selection for changes in threshold responses to the Dl morphogen gradient and confirm the NEE structure/function model.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA.

ABSTRACT
Concentration gradients of morphogenic proteins pattern the embryonic axes of Drosophila by activating different genes at different concentrations. The neurogenic ectoderm enhancers (NEEs) activate different genes at different threshold levels of the Dorsal (Dl) morphogen, which patterns the dorsal/ventral axis. NEEs share a unique arrangement of highly constrained DNA-binding sites for Dl, Twist (Twi), Snail (Sna) and Suppressor of Hairless (Su(H)), and encode the threshold variable in the precise length of DNA that separates one well-defined Dl element from a Twi element. However, NEEs also possess dense clusters of variant Dl sites. Here, we show that these increasingly variant sites are eclipsed relic elements, which were superseded by more recently evolved threshold encodings. Given the divergence in egg size during Drosophila lineage evolution, the observed characteristic clusters of divergent sites indicate a history of frequent selection for changes in threshold responses to the Dl morphogen gradient and confirm the NEE structure/function model.

Show MeSH