Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Mol Biol Evol. 2009 Nov;26(11):2581-93. doi: 10.1093/molbev/msp174. Epub 2009 Aug 3.

Biological sequence simulation for testing complex evolutionary hypotheses: indel-Seq-Gen version 2.0.

Author information

  • 1Department of Computer Science and Engineering, University of Nebraska, NE, USA.


Sequence simulation is an important tool in validating biological hypotheses as well as testing various bioinformatics and molecular evolutionary methods. Hypothesis testing relies on the representational ability of the sequence simulation method. Simple hypotheses are testable through simulation of random, homogeneously evolving sequence sets. However, testing complex hypotheses, for example, local similarities, requires simulation of sequence evolution under heterogeneous models. To this end, we previously introduced indel-Seq-Gen version 1.0 (iSGv1.0; indel, insertion/deletion). iSGv1.0 allowed heterogeneous protein evolution and motif conservation as well as insertion and deletion constraints in subsequences. Despite these advances, for complex hypothesis testing, neither iSGv1.0 nor other currently available sequence simulation methods is sufficient. indel-Seq-Gen version 2.0 (iSGv2.0) aims at simulating evolution of highly divergent DNA sequences and protein superfamilies. iSGv2.0 improves upon iSGv1.0 through the addition of lineage-specific evolution, motif conservation using PROSITE-like regular expressions, indel tracking, subsequence-length constraints, as well as coding and noncoding DNA evolution. Furthermore, we formalize the sequence representation used for iSGv2.0 and uncover a flaw in the modeling of indels used in current state of the art methods, which biases simulation results for hypotheses involving indels. We fix this flaw in iSGv2.0 by using a novel discrete stepping procedure. Finally, we present an example simulation of the calycin-superfamily sequences and compare the performance of iSGv2.0 with iSGv1.0 and random model of sequence evolution.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (7)Free text

F IG . 1.—
F IG . 2.—
F IG . 3.—
F IG . 4.—
F IG . 5.—
F IG . 6.—
F IG . 7.—
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk