Theoretical models Evolution by gene duplication

1 theoretical models

1.1 preservation of gene duplicates

1.1.1 dosage effects
1.1.2 activity reducing mutations


1.2 long-term fate of duplicated genes

1.2.1 neofunctionalization

1.2.1.1 iad model


1.2.2 subfunctionalization

1.2.2.1 ddc model
1.2.2.2 eac model

theoretical models

several models exist try explain how new cellular functions of genes , encoded protein products evolve through mechanism of duplication , divergence. although each model can explain aspects of evolutionary process, relative importance of each aspect still unclear. page presents theoretical models discussed in literature. review articles on topic can found @ bottom.

in following, distinction made between explanations short-term effects (preservation) of gene duplication , long-term outcomes.

preservation of gene duplicates

since gene duplication occurs in 1 cell, either in single-celled organism or in germ cell of multi-cellular organism, carrier (i.e. organism) has compete against other organisms not carry duplication. if duplication disrupts normal functioning of organism, organism has reduced reproductive success (or low fitness) compared competitors , die out rapidly. if duplication has no effect on fitness, might maintained in proportion of population. in cases, duplication of gene might beneficial, providing carrier fitness advantage.

dosage effects

the so-called dosage of gene refers amount of mrna transcripts , subsequently translated protein molecules produced gene per time , per cell. if amount of gene product below optimal level, there 2 kinds of mutations can increase dosage: increases in gene expression promotor mutations , increases in gene copy number gene duplication.

the more copies of same (duplicated) gene cell has in genome, more gene product can produced simultaneously. assuming no regulatory feedback loops exist automatically down-regulate gene expression, amount of gene product (or gene dosage) increase each additional gene copy, until upper limit reached or sufficient gene product available.

furthermore, under positive selection increased dosage, duplicated gene advantageous , increase in frequency in population. in case, no further mutations necessary preserve (or retain) duplicates. however, @ later time, such mutations still occur, leading genes different functions (see below).

gene dosage effects after duplication can harmful cell , duplication might therefore selected against. instance, when metabolic network within cell fine-tuned can tolerate amount of gene product, gene duplication offset balance.

activity reducing mutations

in cases of gene duplications have no immediate fitness effect, retention of duplicate copy still possible if both copies accumulate mutations instance reduce functional efficiency of encoded proteins without inhibiting function altogether. in such case, molecular function (e.g. protein/enzyme activity) still available cell @ least extend available before duplication (now provided proteins expressed 2 gene loci, instead of 1 gene locus). however, accidental loss of 1 gene copy might detrimental, since 1 copy of gene reduced activity lie below activity available before duplication.

long-term fate of duplicated genes

if gene duplication preserved, fate random mutations in 1 duplicate gene copy cause gene become non-functional . such non-functional remnants of genes, detectable sequence homology, can still found in genomes , called pseudogenes.

functional divergence between duplicate genes possible fate. there several theoretical models try explain mechanisms leading divergence:

neofunctionalization

the term neofunctionalization first coined force et al. 1999, refers general mechanism proposed ohno 1970. long-term outcome of neofunctionalization 1 copy retains original (pre-duplication) function of gene, while second copy acquires distinct function. known mdn model, mutation during non-functionality . major criticism of model high likelihood of non-functionalization, i.e. loss of functionality of gene, due random accumulation of mutations.

iad model

iad stands innovation, amplification, divergence , aims explain evolution of new gene functions while preserving existing functions. innovation, i.e. establishment of new molecular function, can occur via promiscuous side-activities of genes , proteins, not optimised do. example, enzymes can catalyse more 1 reaction, though optimised catalysing 1 reaction. such promiscuous protein functions, if provide advantage host organism, can amplified additional copies of gene. such rapid amplification best known bacteria carry genes on smaller non-chromosomal dna molecules (called plasmids) capable of rapid replication. gene on such plasmid replicated , additional copies amplify expression of encoded proteins, , promiscuous function. after several such copies have been made, , passed on descendent bacterial cells, few of these copies might accumulate mutations lead side-activity becoming main activity.

the iad model have been tested in lab using bacterial enzyme dual function starting point. enzyme capable of catalysing not original function, side function can carried out other enzyme. allowing bacteria enzyme evolve under selection improve both activities (original , side) several generations, shown 1 ancestral bifunctional gene poor activities (innovation) evolved first gene amplification increase expression of poor enzyme, , later accumulated more beneficial mutations improved 1 or both of activities can passed on next generation (divergence)

subfunctionalization

subfunctionalization first coined force et al. 1999. model requires ancestral (pre-duplication) gene have several functions (sub-functions), descendant (post-duplication) genes specialise on in complementary fashion. there @ least 2 different models labeled subfunctionalization, ddc , eac .

ddc model

ddc stands duplication-degeneration-complementation . model first introduced force et al. 1999. first step gene duplication. gene duplication in neither advantageous, nor deleterious, remain @ low frequency within population of individuals not carry duplication. according ddc, period of neutral drift may lead complementary retention of sub-functions distributed on 2 gene copies. comes activity reducing (degenerative) mutations in both duplicates, accumulating on time periods , many generations. taken together, 2 mutated genes provide same set of functions ancestral gene (before duplication). however, if 1 of genes removed, remaining gene not able provide full set of functions , host cell suffer detrimental consequences. therefore, @ later stage of process, there strong selection pressure against removing of 2 gene copies arose gene duplication. duplication becomes permanently established in genome of host cell or organism.

eac model

eac stands escape adaptive conflict . name first appeared in publication hittinger , carroll 2007.

the evolutionary process described eac model begins before gene duplication event. singleton (not duplicated) gene evolves towards 2 beneficial functions simultaneously. creates adaptive conflict gene, since unlikely execute each individual function maximum efficiency. intermediate evolutionary result multi-functional gene , after gene duplication sub-functions carried out specialised descendants of gene. end result same under ddc model, 2 functionally specialised genes (paralogs). in contrast ddc model, eac model puts more emphasis on multi-functional pre-duplication state of evolving genes , gives different explanation why duplicated multi-functional genes benefit additional specialisation after duplication (because of adaptive conflict of multi-functional ancestor needs resolved). under eac there assumption of positive selection pressure driving evolution after gene duplication, whereas ddc model requires neutral ( undirected ) evolution take place, i.e. degeneration , complementation.