the traditional concepts, the eukaryotic chromosomes are linear and
the prokaryotic chromosomes are circular. In 1992 we discovered that
the chromosomes of Streptomyces (a class of Gram-positive soil
bacteria) are linear. This discovery stemmed from our studies on the
instability of the Streptomyces chromosomes. The unstable region
turned out to be at the termini of the Streptomyces chromosomes.
The unstable regions of the chromosomes (about 8 Mb) include terminal
inverted repeats of up to several hundreds of kb, and covalently bound
models for circular chromosomes cannot be applied to some important
physiology of the linear bacterial chromosomes (such as replication,
conjugal transfer, and transposition). Therefore, we must improvise
new models and investigate new mechanisms. We have found that the
termini of the chromosomes (and linear plasmids) contain abundant
palindromic sequences capable of forming very special secondary structure
(see figure below). These structures should be involved in the patching
of the telomeres (Replication of the chromosomal DNA from the inside
out would leave gaps at the 3' end that require patching).
We are also
studying how the linear chromosomes and plasmids are transferred during
conjugation. We discovered new transfer mechanisms drastically different
from those of the classical models. The novel mechanisms probably
reflect the behaviors of the linear replicons during evolution, and
can also be used to explain why circular genetic maps are generated
by these linear chromosomes.
produce a wide variety of secondary metabolites including the majority
of known antibiotics. We have studied the involvement of signal transduction
in the regulation of antibiotic biosynthesis, and the genetics and
biochemistry of drug efflux in Streptomyces. We are also investigating
the possibility that linear chromosomes also exit in actinomycetes
other than the streptomycetes, particularly some important pathogens
(such as mycobacteria). If these chromosomes are indeed linear, it
will be of great significance in basic as well as applied research.
initiated cytological studies using modern optical techniques, hoping
to understand how the linear chromosomes are structured, replicated,
and transferred in life cells.