New tools answer biology's big questions

Providing innovative software and database tools for evolutionary and human health discoveries

With a large bank of networked computers at their disposal, bioinformaticians at our Institute are creating new research tools to help answer some of the greatest unanswered questions in science. How and when did life on Earth evolve? How can scientists identify the genes and molecular circuitry in human scourges like cancer? How does an organism develop from a single, fertilized egg into an adult body made up of trillions of cells?

These valuable nuggets of information are buried within worldwide DNA sequence repositories such as GenBank.  Immense streams of DNA data exist, and the complete DNA sequence information for an organism, called a genome, has now been completed for thousands of species. By comparing these DNA sequences with the help of some serious number-crunching supercomputering power, scientists can tease out the answers to some of life's fundamental evolutionary and human health questions.

The goal of our research in comparative genomics is to:

• Understand disease-associated mutations in the context of the long term evolutionary history of disease genes.
• Investigate the relationship between rates of molecular evolution and patterns of gene expression.
• Infer molecular timescales of vertebrate evolution based on protein clocks.

 

Coupling software and database technologies with evolutionary analysis techniques, researchers led by our Center for Evolutionary Functional Genomics are seeking to understand human disease mutations through the lens of molecular evolution. Disease mutations are found to be statistically overabundant in DNA conserved domains and underrepresented in variable regions. This discovery suggests that there is a non-additive influence of protein site conservation on the intragenic distribution of disease mutations. The importance of such findings underscores the merit of large-scale inquiry into patterns of neutral amino acid substitutions over the course of evolution.

The ability to construct a reliable timescale of vertebrate evolution has utility beyond the study of vertebrate species divergence, offering insights to the fields of developmental biology, archaeology, palaeontology and physiology. Our researchers have developed robust methods for inferring a timescale of vertebrate evolution involving the evolutionary analysis of genomic sequence data to estimate rates of molecular and morphological change in light of patterns of macroevolution and biogeography. Molecular clock techniques employed by our researchers find that multigene divergence times for several large orders of mammals coincide closely with fossil-based estimates of species divergence.