NDLI: Detection of weakly conserved ancestral mammalian regulatory sequences by primate comparisons

Content Provider	Springer Nature : BioMed Central
Author	Wang, Qian-fei Prabhakar, Shyam Chanan, Sumita Cheng, Jan-Fang Rubin, Edward M Boffelli, Dario
Abstract	Background Genomic comparisons between human and distant, non-primate mammals are commonly used to identify cis-regulatory elements based on constrained sequence evolution. However, these methods fail to detect functional elements that are too weakly conserved among mammals to distinguish them from non-functional DNA. Results To evaluate a strategy for large scale genome annotation that is complementary to the commonly used distal species comparisons, we explored the potential of deep intra-primate sequence comparisons. We sequenced the orthologs of 558 kb of human genomic sequence, covering multiple loci involved in cholesterol homeostasis, in 6 non-human primates. Our analysis identified six non-coding DNA elements displaying significant conservation among primates but undetectable in more distant comparisons. In vitro and in vivo tests revealed that at least three of these six elements have regulatory function. Notably, the mouse orthologs of these three functional human sequences had regulatory activity despite their lack of significant sequence conservation, indicating that they are ancestral mammalian cis-regulatory elements. These regulatory elements could be detected even in a smaller set of three primate species including human, rhesus and marmoset. Conclusion We have demonstrated that intra-primate sequence comparisons can be used to identify functional modules in large genomic regions, including cis-regulatory elements that are not detectable through comparison with non-mammalian genomes. With the available human and rhesus genomes and that of marmoset, which is being actively sequenced, this strategy can be extended to the whole genome in the near future.
Related Links	https://genomebiology.biomedcentral.com/counter/pdf/10.1186/gb-2007-8-1-r1.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/gb-2007-8-1-r1
Journal	Genome Biology
Issue Number	1
Volume Number	8
Language	English
Publisher	BioMed Central
Publisher Date	2007-01-03
Access Restriction	Open
Subject Keyword	Animal Genetics and Genomics Human Genetics Plant Genetics and Genomics Microbial Genetics and Genomics Bioinformatics Evolutionary Biology Bacterial Artificial Chromosome Additional Data File Functional Sequence Primate Comparison Anthropoid Primate
Content Type	Text
Resource Type	Article
Subject	Biotechnology Genetics
Journal Impact Factor	10.1/2023
5-Year Journal Impact Factor	16.5/2023

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