Krüppel Expression Levels Are Maintained through Compensatory Evolution of Shadow Enhancers.
Many developmental genes are controlled by shadow enhancers—pairs of enhancers that drive overlapping expression patterns. We hypothesized that compensatory evolution can maintain the total expression of a gene, while individual shadow enhancers diverge between species. To test this hypothesis, we analyzed expression driven by orthologous pairs of shadow enhancers from Drosophila melanogaster, Drosophila yakuba, and Drosophila pseudoobscura that control expression of Krüppel, a transcription factor that patterns the anterior-posterior axis of blastoderm embryos. We found that the expression driven by the pair of enhancers is conserved between these three species, but expression levels driven by the individual enhancers are not. Using sequence analysis and experimental perturbation, we show that each shadow enhancer is regulated by different transcription factors. These results support the hypothesis that compensatory evolution can occur between shadow enhancers, which has implications for mechanistic and evolutionary studies of gene regulation.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Zeba
Z
Wunderlich
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Meghan D J
MD
Bragdon
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Ben J
BJ
Vincent
Swarthmore College, Swarthmore, PA 19081, USA.
Jonathan A
JA
White
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Javier
J
Estrada
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: angela_depace@hms.harvard.edu.
Angela H
AH
DePace
D000818:Animals; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male
D029721:Drosophila Proteins; C497244:Kr protein, Drosophila; D051741:Kruppel-Like Transcription Factors