**5.2 Alternative splicing**

44 Gene Duplication

highly asymmetrical. Panchin et al. (2010) show that in human duplicate genes one duplicate appears to remain totally unchanged, while its sibling accumulates the majority of

Contrary to expectations, many gene duplicate pairs appear to be retained despite total apparent functional redundancy. A relatively recent model has been proposed to explain this phenomenon. The theory, coined "originalization", uses arguments based on purifying selection and recombination to support the preservation of both duplicate copies (i.e. prevent non-functionalization) for an extended period of time (Xue & Fu, 2009;

It has also been suggested that models of duplicate retention are focusing on too small a unit, and that protein interaction networks (themselves composed of a number of coexpressed and functionally related proteins) provide a more coherent perspective on the size of perturbation required to have a phenotypically relevant effect (MacCarthy & Bergman, 2007). The authors argue that cases of regulatory subfunctionalization and neofunctionalization often have no phenotypic consequence on the output of a protein network, and are thus effectively neutral for longer than duplicate-oriented models would suggest. A number of studies have reported an unexplained level and duration of retention

The relative importance of these models to the retention of duplicates is a subject of continued interest. Whole genome duplication events, which effectively introduce a paralogous copy of every gene in the genome, present an opportunity to tally the cases for which each model applies best. For a review of the relative importance of these various retention models specifically as they pertain to duplicates produced in plant WGD events,

**5. Factors affecting the rate and trajectory of duplicate gene divergence**

Gene conversion describes the process by which the sequence content of one genetic locus is used as a template to alter and "paste over" the genetic sequence at a distal location. Gene conversion has the potential to enforce similarity across duplicate loci, both in terms of regulation and structure. A recent study on duplicated segments in a pair of *Drosophila* species made noted several anomalies that were suggestive of gene conversion. Interestingly, the edges of duplicated regions accumulated distinguishing mutations faster than more central regions, suggesting that these regions were being maintained by gene conversion and that the size of the region being converted was gradually being reduced by sequence mutations near the borders. Furthermore, paralogs near the boundaries of duplicated segments showed more divergence than those located near the centre (Osada & Innan, 2008). The authors note that this phenomenon could result in misleading estimates of synonymous divergence, as the conversion process would

The requirements for a neofunctionalized gene to escape gene conversion and achieve fixation have been studied from a population genetics perspective (Teshima & Innan, 2008). The fit of the model is tested on a pair of human opsins, which differ in their light

Additional evidence that gene conversion may play a role in duplicate divergence was found in a study of WGD duplicates in rice. Duplicates that contained subsequences of

functional (in this case, amino acid) mutations.

for redundant duplicates (Skamnioti et al., 2008).

periodically homogenize the two sequences.

Xue et al., 2010).

see (Edger & Pires, 2009).

**5.1 Gene conversion** 

sensitivity.

In general, multiple splice forms (and the potential for these splice variants to have distinct functions) have not received much attention in studies of gene duplication and functional divergence. In a first step towards addressing this oversight, Zhan et al. (2011) studied the potential for alternative splicing in *Drosophila* duplicates. New genes tended to show lower levels of alternative splicing, and the subset of duplicates that retained the potential for multiple spliceforms were expressed in fewer tissues, at lower levels, and had had their expression breadth shifted towards preferential expression in testes. The authors also noted that a duplicate's alternative splicing potential depended on duplication mode, with retrotransposed genes being copied with a specific and frozen configuration of exons/introns.
