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Copyright © 1998, MCB UP Limited
Software for gene analysis
Software developed in a bioinformatics project led by Professor Paul Harvey, head of the UK's Oxford University's Zoology Department, has revealed for the first time the evolutionary histories of viruses like HIV and species such as thehumpback whales.
A report in the Research File of the UK's Engineering and Physical Sciences Research Council (EPSRC)'s update Impact, No. 20, 1998, outlines the work of this pioneering new software. New analytical and statistical methods for tracing the dynamics of evolutionary and population processes written into gene sequences have been produced. These approaches have great potential for revealing the evolutionary histories of organisms that have no fossil record. They can also, we are told, help to identify the footprints of mass extinction events, patterns of past epidemics and histories of newly discovered viruses. Professor Harvey is quoted in the report :
These methods can be applied effectively only if researchers have simple access to powerful automatic analyses of the flood of information contained in gene sequence data banks The wide availability of appropriate software will, therefore, be of immense benefit to biologists, ecologists and others in applying current knowledge and resolving outstanding theoretical problems.
One of the vital functions performed by this software is to reconstruct and analyse the "phylogenic trees" which trace the historical development of an organism or species, including the exploration of alternatives to identify an optimal solution. Gene sequences from pairs of individual or species are more similar when they share a recent common ancestor at a node in such a tree. The relative timing and distance apart of the nodes can be used to determine relative rates of reproduction, extinction and species evolution.
An example of the analyses of the hepatitis C virus using Oxford's gene analysis software has been given in the Research File Report already quoted. It outlines four stages:
Edit sequence retrieval and editing of DNA sequences.
Align compilation of homologous DNA sequences from different virus strains into an alignment.
Phylogeny phylogenetic tree of evolutionary relationships is reconstructed from the alignment.
Lineages-through-time the number of lineages plotted through time from which some processes producing genetic diversity can be inferred.
The report also says that:
Tree reconstruction employs "coalescent theory", which works backwards from a small sample, assuming a simple scenario of a constant rate for species evolution and extinction processes. A model of population change calculates the expected time in the past that any two of a present-day sample shared a common ancestor. A sequence of steps involving "coalescing" two individuals reduces the number of lineage branches in the tree, which can identify the common ancestor of an entire sample.
Programs have been built to perform a variety of relevant tasks such as aligning DNA genetic patterns and producing maximium likelihood estimates of factors like extinction rates. A major current focus of the group is to combine programs into an integrated suite.
Programs can be downloaded from the group's Website. They generally run, we are informed, in Apple or Microsoft Windows environments, although access to more powerful workstations might be needed for applications with very large data sets.
The Oxford University's bioinformatics project is scheduled to end in March 2000.The Web Link for contact is: evolve.zoo.ox.ac.uk (Oxford University Zoology research group).