Protein Structure and Function. Application of Bioinformatics Methods - John Rigden 2014

Functional diversity in packing elements and superfamilies
Diversity of functions in homologous proteins
Evolution of protein superfamilies

Ultimately, the core defining criterion for a group of Proteins belonging to the same superfamily is that the genes encoding these proteins descend from a single common ancestral Gene. The process whereby an ancestral gene gives rise to two (or more) copies of itself is generally referred to as duplication.

By definition, a duplication event gives rise to homologous genes. However, a distinction must be made for subsequent Evolutionary Processes. Genes that descend from a common ancestral gene via Gene Duplication without a concomitant speciation process are known as paralogs. Conversely, genes that descend from a common ancestral gene via gene duplication driven by speciation are known as orthologs. It is widely accepted that, due to strong selective pressure, orthologous genes typically retain the function of the ancestral gene, and both descendant species remain capable of carrying out this ancestral function (Tatusov et al. 1997). Based on this assumption, some authors even define orthologs as homologs that perform the exact same function across different species. Several Databases exist that enable the identification of orthologous genes in a variety of organisms (Dolinski and Botstein 2007). On the other hand, the presence of multiple copies of a given gene in The Genome—that is, paralogs—likely exerts strong selective pressure on one copy to retain its original function, thereby providing greater scope for the divergence of the other gene copies. The process by which one copy of a duplicated gene preserves the ancestral function while the remaining copies evolve and acquire new Functions is known as neofunctionalization. Due to a lack of selective pressure during evolutionary divergence, these extra copies frequently degenerate into pseudogenes, which are essentially non-expressing gene relics (Harrison and Gerstein 2002). This evolutionary pathway is termed nonfunctionalization. Subfunctionalization represents a third evolutionary trajectory, denoting instances where the multiple functions of an ancestral gene are partitioned among paralogs. Be that as it may, it is generally held that paralogs possess greater potential for divergence compared to orthologs and, consequently, exhibit a higher degree of functional diversity.

The events following duplication and The Emergence of orthologs and paralogs, regardless of the sequence in which they occurred throughout biological history, ultimately led to the rise of modern protein superfamilies. Apparently, this process was not equally successful for all superfamilies, as certain superfamilies are known to account for a disproportionately large number of genes in fully sequenced genomes (Marsden et al. 2006). To date, the underlying reasons for the varying evolutionary success of different families remain unclear. Various arguments have been proposed relating to Structural and functional properties, as well as evolutionary dynamics (Goldstein 2008). Naturally, one might expect older superfamilies—having had more time to diverge and acquire diverse functions—to be more populous today. For instance, the HUP superfamily (CATH code 3.40.50.620) dates back to the RNA world, as suggested by phylogenetic evidence, and is characterized by an exceptionally wide spectrum of seemingly unrelated functions (Aravind et al. 2002). At the same time, some modern superfamilies found exclusively in eukaryotic species are often restricted to a highly specific repertoire of functions. However, age does not appear to be the primary factor explaining the disparate sizes of superfamilies. A recent study analyzed the evolutionary dynamics of various gene families: some families contained genes associated with core housekeeping functions (E-families), whereas others did not (N-families). It is hypothesized that paralogs within E-families are more likely to evolve and acquire novel functions than those within N-families. This suggests that the ancestral functions of a family's genes are a key determinant of evolutionary success (Shakhnovich and Koonin 2006). As will be discussed in the next section, additional insights into the varying evolutionary success of Protein Families can be gained from the mechanisms proposed to explain the evolution of protein function.