Genetic Redundancy

Genetic redundancy is a term typically used to describe situations where a given biochemical function is redundantly encoded by two or more genes. In these cases, mutations (or defects) in one of these genes will have a smaller effect on the fitness of the organism than expected from the genes’ function. Characteristic examples of genetic redundancy include (Enns, Kanaoka et al. 2005) and (Pearce, Senis et al. 2004). Many more examples are thoroughly discussed in (Kafri, Levy & Pilpel. 2006).

The main source of genetic redundancy was thought to be found in the process of gene duplication which generates multiplicity in gene copy number. However, recent studies concluded that robustness of mutant strains cannot be caused by gene duplication and redundancy, but is more likely to be caused by interactions between unrelated genes . More recent studies have now confirmed that cooperating networks of unrelated genes contribute significantly more to robustness than gene copy number . Another source of genetic redundancy are convergent evolutionary processes leading to genes that are close in function but unrelated in sequence (Galperin, Walker & Koonin 1998).

A Darwinian Paradox Genetic redundancy has aroused significant debate in the context of evolutionary biology (Nowak et al., 1997; Kafri, Springer & Pilpel . 2009). This is because the redundant character of the genes (which are not associated with genetic duplication and which do not mutate faster) seems to defy natural selection. Usually, biologist try to fit their observations into a selection-framework, but here it does not fit.

To understand genetic redundancy and biological robustness we must not think in linear terms of single causality ("natural selection") where A causes B causes C causes D causes E. Rather it must be appreciate that biological systems are scale-free networks. In a scale-free network the distribution of node linkage follows a power law, in that it contains many nodes with a low number of links, few nodes with many links and very few nodes with a high number of links. A scale-free network is very much like the internet: the major part of the websites makes only a few links, less make an intermediate number of links, whereas a minor part makes the majority of links. Usually hundreds of routers routinely malfunction on the Internet at any moment, but the network rarely suffers major disruptions. As many as 80 percent of randomly selected Internet routers can fail and the remaining ones will still form a compact cluster in which there will still be a path between any two nodes . Likewise, genes never operate alone but in redundant scale-free networks with an incredible level of buffering capacity.

A interactive network of cooperating proteins that substitute for or by-pass each other’s functions provide the robustness of biological system. It is hard to imagine how selection acts on individual nodes of a scale-free, redundant genetic system. From an evolutionary standpoint, genes with overlapping functions implies minimal, if any, selective pressures acting on these genes. One therefore expects that the genes participating in such buffering of mutations will be subject to severe mutational drift diverging their functions and/or expression patterns with considerably high rates. Although the functional divergence of paralogous gene pairs can be extremely fast, redundant genes do commonly not mutate faster than essential genes (Winzeler EA et al. 1999; Wagner A, 2000; Kitami T, 2002].

Taking these notions into account, the very existence of genetic buffering, and the functional redundancies required for it, presents a paradox in light of the Darwinian (or: selectionist) concept. On one hand, for genetic buffering to take place there is a necessity for redundancies of gene function, on the other hand such redundancies are clearly unstable in face of natural selection and are therefore unlikely to be found in evolved genomes. Still, over 90% of the genes of studies model organisms were observed to be redundant .