FIRST COMPLETE GENOME SEQUENCED
By Sean Henahan, Access Excellence
A team of researchers have managed to complete a genetic map of
the bacterium Haemophilus influenzae. This accomplishment
represents the first complete genetic
map of a free-living organism and should speed efforts to
sequence the human genome.
The researchers used a new approach called whole genome
shotgun sequencing to sequence the 1,749 genes of the bacterium
in less than a year. The feat would not have been possible in
such a relatively short period of time without impressive new
computer software and hardware.
The H. influenzae project was based on an approach to
genomic analysis using sequencing and assembly of unselected
pieces of DNA from the whole chromosome. The result was the
complete nucleotide sequence- 1,830,137 base pairs. This
approach eliminates the need for initial mapping efforts
involving overlapping 40 kb DNA segments and should be
applicable to mapping other microbial species for which gene
maps do not exist, the researchers note.
Other ongoing genome projects, including the human genome
project are based on the sequencing of clones derived from
mapped restriction fragments, or lambda or cosmid clones. This
approach has been slower, lacking sufficient computations muscle
to support the assembly of the tens of thousands of random
sequences found in a genome into a single assembly.
The current research relied on newly developed software
programs that allowed rapid and accurate sequencing of large
segments of DNA. The so-called 'shot-gun sequencing strategy'
begins with the preparation of a single random DNA fragment
library by first mechanically breaking the organism apart. The
resulting fragments were then sequenced and assembled to produce
the complete genome with the help of a software program called
TIGR ASSEMBLER. .
In addition to a creating a physical map of the genome, the
research team has catalogued many of genes' locations and many
of their functions. Having access to a complete genome will help
researchers determine how living organisms are organized
genetically and how they have evolved. It should also help them
determine the pathogenic elements of the genome.
The map of H. influenza was a nationwide collaboration by a
team of researchers from Johns Hopkins University (including
Nobel Prize winner Hamilton Smith), the State University of New
York in Buffalo, the National Institute of Standards and
Technology and the Institute for Genomic Research.
The success of this approach is also a vindication for study
director Craig Venter of the Institute for Genomic Research.
Others researchers had previously expressed skepticism about the
utility of a database of gene fragments for complete genome
mapping, and the National Institutes of Health had declined to
fund the H. influenzae genome project. The team has now been
invited to collaborate on 30 different microbial genome mapping
Haemophilus influenzae is a Gram-negative bacterium that depends
on a human host. The organisms causes recurring childhood ear
infections and is also linked to meningitis in children.
A vaccine has recently become available for this bacterium.
While this is the first successful mapping a complete
genome sequence of a living organism, researchers have
previously determined the complete genome sequence for several
viruses, including cytomegalovirus, vaccinia and vareola
(smallpox). Indeed, the smallpox virus was the first to be
sequenced using the automated technology.
The current research provides considerable encouragement to
scientists involved in other genome mapping projects. In
addition to the Human Genome Project, scientists are also now
mapping the genomes for E.coli, B. subtilis, C.elegans and
"The success of whole genome shotgun sequencing offers the
potential to accelerate research in a number of areas.
Comparative genomics could be advanced by the availability of an
increased number of complete genomes from a variety of
prokaryotes and eukaryotes," report the researchers.
The new methods used to map H. influenza could lead to
identification of the complete genomes of other pathogenic
organisms. This in turn could lead to the development of new
vaccines. The new strategy should also speed up the sequencing
of the human genome.
For more information on this research see: Science Vol.
269, 7/28/95, Smith et al, pp. 495-511; and associated
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