ScholarlyCommons: Repository

Title

Patterns of Sequence Conservation in Presynaptic Neural Genes

Author(s)

Dexter Hadley, University of Pennsylvania
Tara Murphy, University of Pennsylvania
Otto Valladares, University of Pennsylvania
Sridhar Hannenhalli, University of Pennsylvania
Lyle H. Ungar, University of Pennsylvania
Junhyong Kim, University of Pennsylvania
Maja Bucan, University of Pennsylvania

Document Type

Journal Article

Date of this Version

November 2006

Comments

Reprinted from Genome Biology, Volume 7, Issue 11, November 2006, pages R105.1-R105.19.
Publisher URL: http://genomebiology.com/2006/7/11/R105

Abstract

Background: The neuronal synapse is a fundamental functional unit in the central nervous system of animals. Because synaptic function is evolutionarily conserved, we reasoned that functional sequences of genes and related genomic elements known to play important roles in neurotransmitter release would also be conserved.

Results: Evolutionary rate analysis revealed that presynaptic proteins evolve slowly, although some members of large gene families exhibit accelerated evolutionary rates relative to other family members. Comparative sequence analysis of 46 megabases spanning 150 presynaptic genes identified more than 26,000 elements that are highly conserved in eight vertebrate species, as well as a small subset of sequences (6%) that are shared among unrelated presynaptic genes. Analysis of large gene families revealed that upstream and intronic regions of closely related family members are extremely divergent. We also identified 504 exceptionally long conserved elements (≥360 base pairs, ≥80% pair-wise identity between human and other mammals) in intergenic and intronic regions of presynaptic genes. Many of these elements form a highly stable stem-loop RNA structure and consequently are candidates for novel regulatory elements, whereas some conserved noncoding elements are shown to correlate with specific gene expression profiles. The SynapseDB online database integrates these findings and other functional genomic resources for synaptic genes.

Conclusion: Highly conserved elements in nonprotein coding regions of 150 presynaptic genes represent sequences that may be involved in the transcriptional or post-transcriptional regulation of these genes. Furthermore, comparative sequence analysis will facilitate selection of genes and noncoding sequences for future functional studies and analysis of variation studies in neurodevelopmental and psychiatric disorders.

Keywords

evolution, bioinformatics, neurobiology