5.2.1.1 Gene duplication
It is widely accepted that gene duplication has been one of the main driving forces behind the evolution of multi-gene families. Convergent evolution can not be considered as a major driving force in the production of the wide range of related genes identified throughout
any organisms’ genome. In the context of the evolution of an organism as a whole, gene duplication with subsequent diversification of duplicated products provides the simplest way of acquiring new function. It should be noted that alternative splicing and post- translational modification of a single gene offers an alternative source of simple diversity to that provided by gene duplication (discussed by Ohta, 1991).
Three identified processes can mediate gene duplication. The most frequently described is homologous recombination between repetitive elements, a process that can delete as well as duplicate sections of DNA (reviewed in Purandare and Patel, 1998). In the context of an initial genomic event to produce a gene family via homologous recombination, duplication rather than deletion mediates (although deletion of sequence will act to diversify or remove an established family). Duplication can also occur by non-
homologous recombination induced by chromosomal double stranded breaks, requiring little or no homology between the sites of breakage and repair (Taghian and Nickoloff,
1997). The third process of gene duplication is via RNA-mediated transposition whereby transcribed sequences are integrated into the genome (Vanin, 1985). Once a duplication event has occurred, recombination between the duplicated genes through mis-alignment and unequal crossover can increase or decrease the number of genes within a family.
5.2.1.2 Diversification
The subsequent duplicated products have either diversified to provide alternative function or, as is the case of ribosomal RNA and histone genes, to provide additional, redundant copies necessary for large amounts of the corresponding products.
Diversification of duplicated gene products can result from alternative splicing and post- translational modification of genes or from a direct diversification of the genes
themselves, or a combination of both. An example of extensive post-translational
modification is seen in the proteolytic cleavage of the precursors of opiate peptides (Noda
et al, 1982). The pattern of peptide production from the precursor corticotropin-p- lipotropin differs due to alternative sites of cleavage over developmental stages, enabling the release of a number of different hormones from one gene product.
immunoglobin gene family, an essential component of the vertebrate immune response (Ohta, 1991).
Gene conversion, or gene fusion, is the process of non-reciprocal transfer o f genetic information between two homologous genes. This process does not affect the number of genes within a family but instead alters individual members by the donation o f sequence of one member to another. This has been studied in detail for the p-like globin gene family (reviewed by Papadakis and Patrinos, 1999) where several hemoglobin variants containing fused or hybrid globin chains are described.
In discussing the role of recombination in gene family evolution, Schimenti concludes that the relative frequencies of point mutations compared to the relative frequencies of reciprocal versus nonreciprocal recombination, the number of genes within a family, preferences in donor/recipient gene-conversion pairs, and the frequency of each in the germ line, determines the outcome.
5.2.1.3 Random genetic drift and natural selection
Recombination provides the mechanism for major changes within a eukaryotic organism at the genomic level. Random genetic drift and natural selection contribute to the gradual change of genetic information across evolutionary time. Genetic drift describes the fixation of nucleotide changes through random processes over time, while natural selection describes the fixation or removal of nucleotide changes as a result of selective pressures. Ohta performed computer simulations to determine how a useful gene family can be attained over evolutionary time (summarized by Ohta, 1991). He concludes that positive Darwinian selection (fixation of advantageous changes) is needed, while the interaction between unequal crossover, mutation, random genetic drift, and natural selection are important, for acquiring gene families.
5.2.1.4 Molecular drive
Dover identifies a third passive (non-recombinational) component of genome evolution, molecular drive (Dover, 1982; reviewed in Dover, 1987). M olecular drive describes the unusual rates of DNA turnover within a genome. This is reflected by accelerated
substitution in certain areas of the genome, compared to others and the predicted rate of nucleotide substitution over time. Ohno hypothesized that a redundant, duplicated gene is free to accumulate nucleotide changes without the constraints limiting those associated with the functional copy (Ohno 1970). This plausible notion has not been demonstrated. Instead, whilst studying Xenopus genes, it was demonstrated that as long as a gene is expressed, the functional constraints associated with a single copy gene are operating on that of a duplicated gene (Hughes and Hughes, 1993).
Accelerated amino acid substitution has been associated with gene duplication (Ohta, 1991). This would support diversification under functional constraints - if a gene product is unable to freely acquire changes over time then directed substitutions would increase the chances of diversification.
5.2.1.5 Block duplication
It has been proposed that complex genomes underwent several rounds of genome duplication via polyploidization during evolution (Ohno, 1970). It was first proposed by Lundin that this polyploidization was responsible for the presence of paralogous regions of the genome harboring similar gene families (Lundin, 1993). This idea was further developed by the identification of ten gene families having members on both human chromosomes 6, 9 (Kasahara et al, 1996) This paralogy was seen to also extend to chromosome 1 with examples of four members of these ten gene families (Katsanis et al,
1996). However Hughes and Yeager rejected the idea of simple block duplications by phylogenetic analysis of the gene families (Hughes and Yeager, 1997; Yeager and Hughes, 1999). They demonstrated that in fact the genes had duplicated at widely different time periods, spread over 1.6 billion years. A cautionary comment was made that the original theory of polyploidization (Ohno, 1970) was based on the genome sizes of evolutionarily distant organisms. It was suggested that the relative genome size could have resulted from specialized functions of the particular organisms studied (Hughes and Yeager, 1997).