Gene redundancy

As the genome replicates over many generations, the redundant gene's function will most likely evolve due to Genetic drift. Genetic drift influences genetic redundancy by either eliminating variants or fixing variants in the population.[12] In the event that genetic drift maintains the variants, the gene may accumulate mutations that change the overall function.[14] However, many redundant genes may diverge but retain original function by mechanisms such as subfunctionalization, which preserves original gene function albeit by complementary action of the duplicates.[13][12] The three mechanisms of functional divergence in genes are nonfunctionalization (or gene loss), neofunctionalization and subfunctionalization.[11]

During nonfunctionalization, or degeneration/gene loss, one copy of the duplicated gene acquires mutations that render it inactive or silent. Non-functionalization is often the result of single gene duplications.[11] At this time, the gene has no function and is called a pseudogene. Pseudogenes can be lost over time due to genetic mutations. Neofunctionalization occurs when one copy of the gene accumulates mutations that give the gene a new, beneficial function that is different than the original function. Subfunctionalization occurs when both copies of the redundant gene acquire mutations. Each copy becomes only partially active; two of these partial copies then act as one normal copy of the original gene. Figure 2 to the right provides a visualization of this concept.

Transposable elements play various roles in functional differentiation. By enacting recombination, transposable elements can move redundant sequences in the genome.[15] This change in sequence structure and location is a source of functional divergence.[15] Transposable elements potentially impact gene expression, given that they contain a sizeable amount of micro-RNAs.[15]

Researchers often use the history of redundant genes in the form of gene families to learn about the phylogeny of a species. It takes time for redundant genes to undergo functional diversification; the degree of diversification between orthologs tells us how closely related the two genomes are. Gene duplication events can also be detected by looking at increases in gene duplicates.

A good example of using gene redundancy in evolutionary studies is the Evolution of the KCS gene family in plants. This paper studies how one KCS gene evolved into an entire gene family via duplication events. The number of redundant genes in the species allows researchers to determine when duplication events took place and how closely related species are.

Currently, there are three ways to detect paralogs in a known genomic sequence: simple homology (FASTA), gene family evolution (TreeFam) and orthology (eggNOG v3). Researchers often construct phylogenies and utilize microarrays to compare the structures of genomes to identify redundancy.[18] Methods like creating syntenic alignments and analysis of orthologous regions are used to compare multiple genomes. Single genomes can be scanned for redundant genes using exhaustive pairwise comparisons.[18] Before performing more laborious analyses of redundant genes, researchers typically test for functionality by comparing open reading frame length and the rates between silent and non-silent mutations.[18] Since the Human Genome Project's completion, researchers are able to annotate the human genome much more easily. Using online databases like the Genome Browser at UCSC, researchers can look for homology in the sequence of their gene of interest.

The mode of duplication by which redundancy occurs has been found to impact the classifications in breast cancer disposition genes.[19] Gross duplications complicate clinical interpretation because it is difficult to discern if they occur in tandem. Recent methods, like DNA breakpoint assay, have been used to determine tandem status.[19] In turn, these tandem gross duplications can be more accurately screened for pathogenic status.[19] This research has important implications for evaluating risk of breast cancer.[19]

Researchers have also identified redundant genes that confer selective advantage on the organismal level. The partial ARM1 gene, a redundant gene resulting from a partial duplication, has been found to confer resistance to Blumeria graminis, a mildew fungus.[20] This gene exists in members of the Triticeae tribe, including wheat, rye, and barley.[20]

The Human Olfactory Receptor (OR) gene family contains 339 intact genes and 297 pseudogenes. These genes are found in different locations throughout the genome, but only about 13% are on different chromosomes or on distantly spaced loci. 172 subfamilies of OR genes have been found in humans, each at its own loci. Because the genes in each of these subfamilies are structurally and functionally similar, and in close proximity to each other, it is hypothesized that each evolved from single genes undergoing duplication events. The high number of subfamilies in humans explains why we are able to recognize so many odors.

Human OR genes have homologues in other mammals, such as mice, that demonstrate the evolution of Olfactory Receptor genes. One particular family that is involved in the initial event of odor perception has been found to be highly conserved throughout all of vertebrate evolution.[21]

Duplication events and redundant genes have often been thought to have a role in some human diseases. Large scale whole genome duplication events that occurred early in vertebrate evolution may be the reason that human monogenic disease genes often contain a high number of redundant genes. Chen et al. hypothesizes that the functionally redundant paralogs in human monogenic disease genes mask the effects of dominant deleterious mutations, thereby maintaining the disease gene in the human genome.[22]

Whole genome duplications may be a leading cause of retention of some tumor causing genes in the human genome.[23] For example, Strout et al.[24] have shown that tandem duplication events, likely via homologous recombination, are linked to acute myeloid leukemia. The partial duplication of the ALL1 (MLL) gene is a genetic defect has been found in patients with acute myeloid leukemia.