Molecular mechanisms of epistasis within and between genes

 

 

 Epistasis - (Greek, to stand upon or stop) First introduced by Bateson (1909). Epistasis is a form of gene interaction in which one gene masks the phenotypic expression of another. If one gene locus prevents the expression of a second gene, the first locus is epistatic to the second, and the second is hypostatic to the first. Epistasis can be described as either recessive epistasis or dominant epistasis and alleviating or aggravating.

 

               Epistatic interactions can occur both within and between genes this is confirmed by studying in model organism’s show that they are extremely prevalent in many organism. Epistasis between the genes  in  Salmonella typhimurium, the ribosomal subunits 50 S and 30 S are involving interactions between L19 and L14 proteins and rRNA shows that interactions between changes in interaction interfaces is a cause for epistasis. Genetic redundancy can easily arise through gene duplication, and gene duplicates are indeed very likely to have strong negative epistatic interactions. If an essential metabolite is produced by a linear metabolic pathway the inactivation of a second gene in the pathway can have no further consequence. Thus, in linear pathways null mutations are expected to interact with strong antagonistic epistasis. Genetic hubs can cause epistasis.

 

            Epistatic interaction can also observe within the gene by many molecular mechanisms. Synergistic epistasis can also occur when a conformation change is required for a beneficial (or detrimental) mutation to realize its effect on protein function. Combinations of mutations within a gene can additively affect protein function but still interact epistatically to alter fitness or a phenotype. The gene can be a promiscuous intermolecular suppressor of genetic variation, so mutations within a molecule can lead to epistasis. Epistatic interactions depend on both the environment and the genetic context.

 

            The molecular mechanisms that can cause epistatic interactions are therefore diverse, and still remain to be fully explored in future work. One additional important observation is that epistatic interactions are themselves often highly context-dependent. It has been argued that phenotypic variation in a population in many cases accounted for by purely additive genetic models. However, this is only a theoretical possibility, and it contradicts both the demonstrated importance of epistasis in particular human diseases and the pervasive epistasis that has been detected in model organisms and highlighted here. It is also somewhat inconsistent with patterns of sequence evolution and inconsistent with our understanding of molecular biology and the abundance of nonlinear regulatory interactions.

 

 

Key words: Epistasis, fitness, mutations, Hsp90, redundancy.

 

References:

1.      Bateson, W., 1909, Mendel’s principles of heredity. Cambridge University Press., 270-298.

2.      Benjamin, V. S., Jeremy, B. and Gabriel, M., 2010, Genetic interactions reveal the evolutionary          

            trajectories of duplicate genes. Molecular Systems Biology., 6:429.

3.      Huang, L.S. and Sternberg, P.W., 1995, Genetic dissection of developmental pathways. San Diego:

           Academic Press., 48: 97–122.

4.       Lunzer, M. and Miller,S.P., 2005, The biochemical architecture of an ancient adaptive landscape.Science., 310: 499.

5.      Ortlund, E.A. and  Bridgham, J.T., 2007, Crystal structure of an ancient protein: evolution by

           conformational epistasis. Science., 317: 1544–1548.

6.      Rongmin, Z., Mike, D. and  Chieh, H., 2005, Navigating the chaperone network: an integrative map of physical and genetic interactions mediated by the Hsp90 chaperone. Cell., 120: 715–727.

7.      Sophie, M. P., Wilhelm, P., Alexandra, P. and  Andersson, D.I., 2010, Compensatory  evolution reveals functional interactions between ribosomal proteins S12, L14 and L19. Science., 327:425-431.