Non-technical exposition of one of the leading problems in biology as intended for other disciplines.
Recent experimental and theoretical approaches have attempted to quantify the
physical organization (compaction and geometry) of the bacterial chromosome
with its complement of proteins (the nucleoid). The genomic DNA exists in a
complex and dynamic protein-rich state, which is highly organised at various
length scales. This has implications on modulating (when not enabling) the core
biological processes of replication, transcription, segregation. We overview
the progress in this area, driven in the last few years by new scientific ideas
and new interdisciplinary experimental techniques, ranging from high space- and
time-resolution microscopy to high-throughput genomics employing sequencing to
map different aspects of the nucleoid-related interactome. The aim of this
review is to present the wide spectrum of experimental and theoretical findings
coherently, from a physics viewpoint. We also discuss some attempts of
interpretation that unify different results, highlighting the role that
statistical and soft condensed matter physics, and in particular classic and
more modern tools from the theory of polymers, plays in describing this system
of fundamental biological importance, and pointing to possible directions for
future investigation.
http://arxiv.org/abs/1204.3518
This review discusses challenges that arise in the biological arena, but where we think that mature experimental and theoretical tools from the physical sciences can now allow significant progress. The review is primarily aimed at our colleagues in the physical sciences: it should communicate a feel for the main questions and the main challenges, and our understanding that a comprehensive physical approach is possible and necessary at this point. We will not explain the physical models in great technical detail, and we hope this work will also be of interest to biologists who could take the references given here as a starting point and a "compass" in order to evaluate different modelling approaches. Ultimately, we believe that optimal progress in this area will take place in collaboration, and this review might contribute to establishing a common ground and language.
Finally, it is important to point out that within the layered information given here there lies more than one unresolved question. For example, if macrodomains are microphases struc- tured by protein binding, then certainly these proteins must play an important role in the configurational entropy of the nucleoid, which is not considered in the arguments concerning entropy-driven chromosome segregation. Also, if the genome is compacted (at least in a range of scales) in a fractal or conventional globule configuration by attractive interactions of en- tropic or energetic origin, this will greatly affect its entropy, and thus its mechanical properties, loci dynamics and the interactions between segregating chromosomes. Equally important, the supercoiling-independent size of structural units measured for purified nucleoids (whose size varies with supercoiling) appears challenging for theoretical explanations. While we are cer- tainly far from a coherent and consistent physical description of the nucleoid, there is a clear abundance of existing data and many ongoing experiments merging quantitative biophysics and high-throughput molecular biology. These emerging results, together with the fragmented but partially successful modeling approaches, make us believe that we might be on the verge of resolving at least some of the existing issues regarding the physics of the bacterial nucleoid.
