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High-throughput Identification of Gene Regulatory Sequences Using Next-generation Sequencing of Circular Chromosome Conformation Capture (4C-seq)
Published on: October 5, 2018
Big genomes facilitate the comparative identification of regulatory elements
Brant K Peterson1, Emily E Hare, Venky N Iyer
1Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
Plos One
|March 5, 2009
Summary
Comparative genomics struggles to find invertebrate regulatory sequences due to small genomes. Larger tephritid fly genomes reveal conserved non-coding DNA, aiding regulatory element identification in fruit flies.
Area of Science:
- Genomics
- Evolutionary Biology
- Developmental Biology
Background:
- Identifying regulatory sequences in animal genomes is challenging.
- Comparative genomics using evolutionary conservation excels in vertebrates but struggles in invertebrates.
- This difficulty is often wrongly attributed to fundamental differences in regulatory sequences.
Purpose of the Study:
- To investigate why comparative genomics is less successful in identifying invertebrate regulatory sequences.
- To demonstrate that genome size, not fundamental sequence differences, explains this disparity.
- To explore the utility of larger invertebrate genomes for regulatory sequence discovery.
Main Methods:
- Sequencing and comparing loci involved in early embryonic patterning in four Tephritidae species with larger genomes.
- Analyzing patterns of non-coding DNA conservation in tephritids compared to Drosophila melanogaster.
- Testing the enhancer activity of conserved and non-conserved tephritid non-coding sequences in transgenic Drosophila melanogaster embryos.
Main Results:
- Tephritid genomes, larger than Drosophila, exhibit blocks of conserved non-coding sequences similar to vertebrates, flanked by poorly conserved regions.
- Six of nine tested conserved tephritid non-coding sequences functioned as enhancers in Drosophila embryos.
- None of the tested non-conserved tephritid non-coding sequences showed enhancer activity.
Conclusions:
- The differential success of comparative genomics in finding regulatory sequences is primarily due to the genome size of the species studied, not inherent differences between vertebrate and invertebrate sequences.
- Comparing larger invertebrate genomes, like those of tephritids, can systematically annotate non-coding regions and identify functional regulatory elements.
- Larger genomes should be prioritized in comparative genomics to enhance the detection of functional non-coding DNA and provide a more comprehensive view of genome evolution and function.
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