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posted 15. September 2005 09:01
Evidence of a Large-Scale Functional Organization of Mammalian Chromosomes
Petko M. Petkov, Joel H. Graber, Gary A. Churchill, Keith DiPetrillo, Benjamin L. King, Kenneth Paigen
Received: May 16, 2005; Accepted: August 3, 2005; Published: September 9, 2005
DOI: 10.1371/journal.pgen.0010033
Copyright: © 2005 Petkov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
* To whom correspondence should be addressed. E-mail: ken@jax.org
Synopsis
The arrangement of genes along chromosomes affects their function as well as the likelihood that particular combinations of genes will be inherited together, and evolution has had many millions of years to optimize these arrangements. Because the arrangements are nearly identical in all mammals, one can use the powerful techniques of mouse genetics to explore their roles in our own genomes. The authors find that genes that cooperate in bringing about various cellular and physiological functions, such as immune responses, are often clustered together on chromosomes, and that detailed maps of these relationships can be built. The new techniques have proven so powerful that they can identify functional interactions among genes that are not even on the same chromosome. Beyond illuminating the evolutionary pressures that brought them about, mapping these arrangements will be of great utility in the ongoing searches in many laboratories for the genes underlying our common diseases, such as cancer, heart disease, and diabetes.
Paragraph 4 of Discussion
It is difficult to escape the conclusion that the selective factors acting to generate LD domains and networks during inbreeding reflect clustering and/or interaction of functionally related elements along chromosomes, thereby providing an opportunity for expanding our limited knowledge of the forces that drive molecular evolution in general, and coadaptation of alleles in particular. Chromosome maps and pathway networks are reflections of each other, with the potential of being mutually informative.
Concluding Paragraph
What is notable about our present results is the extent to which functional clustering appears to be present in the mammalian genome. However, what must be emphasized is that while the LD domains of mice have been valuable in leading to this view, their sharply delimited edges probably reflect the particular selection pressures of inbreeding mice in a laboratory environment, rather than evolutionary forces in general. It is likely that functional clustering is as common in the non-domain regions, but less apparent, as it is not under inbreeding selection. Accepting this broader role for evolutionary selection suggests the possibility that all, or nearly all, of the mammalian genome is a linear continuum of functionally related elements and that clusters of functionally related genes may well be interdigitated among each other. Indeed, virtually every search for the many loci underlying complex traits not under laboratory selection, such as disease susceptibility, has revealed multiple epistatic interactions. The functional anatomy of the mammalian genome must be more complex than the fraction we have been able to observe so far.
Citation: Petkov PM, Graber JH, Churchill GA, DiPetrillo K, King BL, et al. (2005) Evidence of a Large-Scale Functional Organization of Mammalian Chromosomes . PLoS Genet 1(3): e33
Read the full research article at PLoS Genetics
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