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Abstract
BackgroundMulti-genome comparative analysis has yielded important insights into the molecular details of gene regulation. We have developed EvoPrinter, a web-accessed genomics tool that provides a single uninterrupted view of conserved sequences as they appear in a species of interest. An EvoPrint reveals with near base-pair resolution those sequences that are essential for gene function.ResultsWe describe here EvoPrinterHD, a 2nd-generation comparative genomics tool that automatically generates from a single input sequence an enhanced view of sequence conservation between evolutionarily distant species. Currently available for 5 nematode, 3 mosquito, 12 Drosophila, 20 vertebrate, 17 Staphylococcus and 20 enteric bacteria genomes, EvoPrinterHD employs a modified BLAT algorithm [enhanced-BLAT (eBLAT)], which detects up to 75% more conserved bases than identified by the BLAT alignments used in the earlier EvoPrinter program. The new program also identifies conserved sequences within rearranged DNA, highlights repetitive DNA, and detects sequencing gaps. EvoPrinterHD currently holds over 112 billion bp of indexed genomes in memory and has the flexibility of selecting a subset of genomes for analysis. An EvoDifferences profile is also generated to portray conserved sequences that are uniquely lost in any one of the orthologs. Finally, EvoPrinterHD incorporates options that allow for (1) re-initiation of the analysis using a different genome's aligning region as the reference DNA to detect species-specific changes in less-conserved regions, (2) rapid extraction and curation of conserved sequences, and (3) for bacteria, identifies unique or uniquely shared sequences present in subsets of genomes.ConclusionEvoPrinterHD is a fast, high-resolution comparative genomics tool that automatically generates an uninterrupted species-centric view of sequence conservation and enables the discovery of conserved sequences within rearranged DNA. When combined with cis-Decoder, a program that discovers sequence elements shared among tissue specific enhancers, EvoPrinterHD facilitates the analysis of conserved sequences that are essential for coordinate gene regulation.
Highlights
Multi-genome comparative analysis has yielded important insights into the molecular details of gene regulation
Comparative analysis of orthologous DNA has revealed that many cis-regulatory enhancers contain multi-species conserved sequences (MCSs) that are essential for their transcriptional regulation
The following is a description of the sequential steps and accompanying algorithms used by EvoPrinterHD to identify conserved sequences shared among multiple genomes
Summary
Multi-genome comparative analysis has yielded important insights into the molecular details of gene regulation. We have developed EvoPrinter, a web-accessed genomics tool that provides a single uninterrupted view of conserved sequences as they appear in a species of interest. An EvoPrint reveals with near base-pair resolution those sequences that are essential for gene function. Comparative analysis of orthologous DNA has revealed that many cis-regulatory enhancers contain multi-species conserved sequences (MCSs) that are essential for their transcriptional regulation (reviewed by [1,2,3,4]). Generated from superimposition of multiple pair-wise BLAT alignments [6], an EvoPrint provides an ordered uninterrupted representation of conserved sequences as they exist in the genome of interest. EvoPrinterHD is a second-generation alignment tool that automates the comparative analysis to rapidly identify a significantly higher percentage of conserved sequences shared among evolutionarily distant orthologs even if they exist within rearranged DNA. The uninterrupted readout allows for the rapid extraction and automated curation of conserved DNA from the genome of interest
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