Subfunctionalization

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Subfunctionalization is a neutral mutation process in which each paralog retains a subset of its original ancestral function. The figure illustrates that the ancestral gene (orange & blue) is capable of both functions before gene duplication. After gene duplication the functional capabilities are divided amongst the gene copies. After this divergence each paralog is capable of independently performing a distinct ancestral function. Subfunctionalization.PNG
Subfunctionalization is a neutral mutation process in which each paralog retains a subset of its original ancestral function. The figure illustrates that the ancestral gene (orange & blue) is capable of both functions before gene duplication. After gene duplication the functional capabilities are divided amongst the gene copies. After this divergence each paralog is capable of independently performing a distinct ancestral function.

Subfunctionalization was proposed by Stoltzfus (1999) [1] and Force et al. (1999) [2] as one of the possible outcomes of functional divergence that occurs after a gene duplication event, in which pairs of genes that originate from duplication, or paralogs, take on separate functions. [3] [4] [5] [6] [7] Subfunctionalization is a neutral mutation process of constructive neutral evolution; meaning that no new adaptations are formed. [8] [7] During the process of gene duplication paralogs simply undergo a division of labor by retaining different parts (subfunctions) of their original ancestral function. [9] This partitioning event occurs because of segmental gene silencing leading to the formation of paralogs that are no longer duplicates, because each gene only retains a single function. [7] It is important to note that the ancestral gene was capable of performing both functions and the descendant duplicate genes can now only perform one of the original ancestral functions. [7]

Contents

Alternative Hypothesis

Subfunctionalization after gene duplication is thought to be the newer model of functional divergence. [10] Before 1910, scientists were unaware that genes were capable of multifunctionalization. [7] The original thought was that each gene possessed one function, but in fact genes have independently mutable regions and possessed the ability to subfunctionalize. [11] [7] Neofunctionalization, where one paralogous copy derives a new function after gene duplication, is thought to be the classical model of functional divergence. [11] Nevertheless, because of its neutral mutation process subfunctionalization seem to present a more parsimonious explanation for the retention of duplicates in a genome. [6] [12] [13]

Specialization

Specialization is a unique model of subfunctionalization, in which paralogs divide into various areas of specialty rather than function. In this model both gene copies perform exactly the same ancestral function. For instance, while the ancestral gene may have performed its function in all tissues, developmental stage, and environmental conditions, the paralogous genes become specialists, dividing themselves among different tissues, developmental stages, and environmental conditions. [14] For example, if the ancestral gene is responsible for both digestive and lymphatic regulatory processes, after gene duplication one of the paralogs would claim responsibility for lymphatic regulation and the other for digestive regulation. Specialization is also unique in the fact that it is a positive rather than neutral mutation process. [7] When a gene specializes among different tissues, developmental stages, or environmental conditions it acquires an improvement in function. Isozymes are a good example of this because they are gene products of paralogs that catalyze the same biochemical reaction. [14] However, different members have evolved particular adaptations to different tissues or different developmental stages that enhance the physiological fine-tuning of the cell. [7]

Gene Sharing

Gene sharing occurs when a gene acquires a secondary function during its evolutionary process. Gene sharing is unique because the gene maintains and performs both its ancestral function and its acquired function. Gene duplication is not necessary in this model, as the addition of functionality occurs before, or often instead of gene duplication. Gene sharing is a fairly common occurrence and is most often seen in enzymes taking on a various subfunctions such as signal transduction and transcriptional regulation. [7] The most noteworthy example of gene sharing is crystallins, the proteins responsible for transparency and diffraction in the eye lens, which have also been found to serve as a metabolic enzyme in other tissue. [7]

Escape from adaptive conflict

Adaptive conflict arises in gene sharing when an improvement to one gene function severely impairs another function. This occurs because selective constraints are particularly stringent in the case of gene sharing. [7] It is very difficult for either function to undergo morphological changes, due to the fact that both the ancestral and novel functions are needed. As a result of its dual function the gene is subjected to two or more independent sets of evolutionary pressure. [7] This means that positively selecting for improvements in one function is likely to cause deleterious effect in the other function. There are two solutions to the predicament of adaptive conflict. The gene can either completely lose its new function or undergo gene duplication followed by subfunctionalization, [7] also called "function splitting". [15]

Duplication-Degeneration-Complementation

In the Duplication- Degeneration- Complementation (DDC) model of subfunctionalization both gene copies are needed to perform the original ancestral function. [10] In this model after a duplication event, both paralogs suffer deleterious mutations leading to functional degradation. This degradation is so severe that neither gene copy can perform the ancestral function or any subset of that function independently. In order to be functional, the paralogs must work together to perform the ancestral task. This teamwork among paralogs is possible because the subfunction lost in one gene copy is complemented in the other gene copy. [7] This functional sharing would not be possible if both paralogs had lost identical subfunctions. The degeneration and complementation processes make the DDC model a selectively neutral mutation process. The mutations accumulated in both paralogs would have been deleterious if they had not been complemented by the other copy. [7] One example of the DDC model is when functionally similar paralogs are expressed at such low levels that both copies are required to produce sufficient amounts of the original gene product. [7]

Segregation avoidance

Segregation avoidance occurs when an unequal crossing over event leads to a locus duplication containing two heterogeneous alleles creating a situation akin to permanent heterozygosity. [7] This occurs primarily in situations of overdominant selection where the heterozygote has increased fitness but less fit homozygotes are still retained in the population. [7] Segregation avoidance addresses the issue of segregational load, wherein the mean fitness of the population is less than the highest possible fitness. The unequal crossing over and subsequent duplication of a locus containing heterogeneous alleles ensures the highest possible fitness. By avoiding homogeneous alleles organisms in the population can benefit from the advantages that both alleles have to offer. A prime example is the ace-1 locus in house mosquitoes, Culex pipiens. [16] Because of segregation avoidance house mosquitos are able to benefit from ace-1R pesticide resistant allele during pesticide exposure and ace-1S wild-type allele during non-exposure. [7] This duality is particularly useful, as the mutant allele causes decreased fitness during period's non-exposure. [16]

Hemoglobin

Human hemoglobin provides a variety of subfunctionalization examples. For instance, the gene for hemoglobin α-chain is undoubtedly derived from a duplicate copy of hemoglobin β-chain. [7] However, neither chain can function independently to form a monomeric hemoglobin molecule, that is a molecule consisting entirely of α-chains or entirely of β-chains. [7] Conversely, hemoglobin consists of both α and β chains, with α2-β2 being among the most efficient forms of hemoglobin in the human genome. This is a prime example of subfunctionalization. Another good example is the emergence of fetal hemoglobin from embryonic hemoglobin after duplication of the hemoglobin γ- chain. [7] This example of subfunctionalization illustrates how different forms of hemoglobin are present at various developmental stages. In fact, there is distinct hemoglobin at each developmental stage: ζ2-ε2 and α2-ε2 in the embryo, α2-γ2 in the fetus, and α2-β2 and α2-δ2 in adults. [7] Each type of hemoglobin has advantages that are particular to the developmental stage in which it thrives. For example, embryonic and fetal hemoglobin have higher oxygen affinity than adult hemoglobin giving them improved functionality in hypoxic environments such as the uterus. [7]

See also

Related Research Articles

Microevolution is the change in allele frequencies that occurs over time within a population. This change is due to four different processes: mutation, selection, gene flow and genetic drift. This change happens over a relatively short amount of time compared to the changes termed macroevolution.

<span class="mw-page-title-main">Mutation</span> Alteration in the nucleotide sequence of a genome

In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosis, or meiosis or other types of damage to DNA, which then may undergo error-prone repair, cause an error during other forms of repair, or cause an error during replication. Mutations may also result from insertion or deletion of segments of DNA due to mobile genetic elements.

<span class="mw-page-title-main">Dominance (genetics)</span> One gene variant masking the effect of another in the other copy of the gene

In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second is called recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes (autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child. Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance, such as incomplete dominance, in which a gene variant has a partial effect compared to when it is present on both chromosomes, and co-dominance, in which different variants on each chromosome both show their associated traits.

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, the evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

<span class="mw-page-title-main">Neutral theory of molecular evolution</span>

The neutral theory of molecular evolution holds that most evolutionary changes occur at the molecular level, and most of the variation within and between species are due to random genetic drift of mutant alleles that are selectively neutral. The theory applies only for evolution at the molecular level, and is compatible with phenotypic evolution being shaped by natural selection as postulated by Charles Darwin.

Population genetics is a subfield of genetics that deals with genetic differences within and among populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and population structure.

<span class="mw-page-title-main">Pseudogene</span> Functionless relative of a gene

Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by gene duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes are usually identified when genome sequence analysis finds gene-like sequences that lack regulatory sequences needed for transcription or translation, or whose coding sequences are obviously defective due to frameshifts or premature stop codons. Pseudogenes are a type of junk DNA.

Gene duplication is a major mechanism through which new genetic material is generated during molecular evolution. It can be defined as any duplication of a region of DNA that contains a gene. Gene duplications can arise as products of several types of errors in DNA replication and repair machinery as well as through fortuitous capture by selfish genetic elements. Common sources of gene duplications include ectopic recombination, retrotransposition event, aneuploidy, polyploidy, and replication slippage.

<span class="mw-page-title-main">Gene family</span> Set of several similar genes

A gene family is a set of several similar genes, formed by duplication of a single original gene, and generally with similar biochemical functions. One such family are the genes for human hemoglobin subunits; the ten genes are in two clusters on different chromosomes, called the α-globin and β-globin loci. These two gene clusters are thought to have arisen as a result of a precursor gene being duplicated approximately 500 million years ago.

<span class="mw-page-title-main">Sequence homology</span> Shared ancestry between DNA, RNA or protein sequences

Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speciation event (orthologs), or a duplication event (paralogs), or else a horizontal gene transfer event (xenologs).

<span class="mw-page-title-main">Paleopolyploidy</span> State of having undergone whole genome duplication in deep evolutionary time

Paleopolyploidy is the result of genome duplications which occurred at least several million years ago (MYA). Such an event could either double the genome of a single species (autopolyploidy) or combine those of two species (allopolyploidy). Because of functional redundancy, genes are rapidly silenced or lost from the duplicated genomes. Most paleopolyploids, through evolutionary time, have lost their polyploid status through a process called diploidization, and are currently considered diploids, e.g., baker's yeast, Arabidopsis thaliana, and perhaps humans.

<span class="mw-page-title-main">Gene</span> Sequence of DNA or RNA that codes for an RNA or protein product

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<span class="mw-page-title-main">Gene cluster</span>

A gene family is a set of homologous genes within one organism. A gene cluster is a group of two or more genes found within an organism's DNA that encode similar polypeptides, or proteins, which collectively share a generalized function and are often located within a few thousand base pairs of each other. The size of gene clusters can vary significantly, from a few genes to several hundred genes. Portions of the DNA sequence of each gene within a gene cluster are found to be identical; however, the resulting protein of each gene is distinctive from the resulting protein of another gene within the cluster. Genes found in a gene cluster may be observed near one another on the same chromosome or on different, but homologous chromosomes. An example of a gene cluster is the Hox gene, which is made up of eight genes and is part of the Homeobox gene family.

<span class="mw-page-title-main">Gene redundancy</span>

Gene redundancy is the existence of multiple genes in the genome of an organism that perform the same function. Gene redundancy can result from gene duplication. Such duplication events are responsible for many sets of paralogous genes. When an individual gene in such a set is disrupted by mutation or targeted knockout, there can be little effect on phenotype as a result of gene redundancy, whereas the effect is large for the knockout of a gene with only one copy. Gene knockout is a method utilized in some studies aiming to characterize the maintenance and fitness effects functional overlap.

Functional divergence is the process by which genes, after gene duplication, shift in function from an ancestral function. Functional divergence can result in either subfunctionalization, where a paralog specializes one of several ancestral functions, or neofunctionalization, where a totally new functional capability evolves. It is thought that this process of gene duplication and functional divergence is a major originator of molecular novelty and has produced the many large protein families that exist today.

Evolution by gene duplication is an event by which a gene or part of a gene can have two identical copies that can not be distinguished from each other. This phenomenon is understood to be an important source of novelty in evolution, providing for an expanded repertoire of molecular activities. The underlying mutational event of duplication may be a conventional gene duplication mutation within a chromosome, or a larger-scale event involving whole chromosomes (aneuploidy) or whole genomes (polyploidy). A classic view, owing to Susumu Ohno, which is known as Ohno model, he explains how duplication creates redundancy, the redundant copy accumulates beneficial mutations which provides fuel for innovation. Knowledge of evolution by gene duplication has advanced more rapidly in the past 15 years due to new genomic data, more powerful computational methods of comparative inference, and new evolutionary models.

<span class="mw-page-title-main">Unequal crossing over</span> Chromosomal crossover resulting in gene duplication or deletion

Unequal crossing over is a type of gene duplication or deletion event that deletes a sequence in one strand and replaces it with a duplication from its sister chromatid in mitosis or from its homologous chromosome during meiosis. It is a type of chromosomal crossover between homologous sequences that are not paired precisely. Normally genes are responsible for occurrence of crossing over. It exchanges sequences of different links between chromosomes. Along with gene conversion, it is believed to be the main driver for the generation of gene duplications and is a source of mutation in the genome.

<span class="mw-page-title-main">Neofunctionalization</span>

Neofunctionalization, one of the possible outcomes of functional divergence, occurs when one gene copy, or paralog, takes on a totally new function after a gene duplication event. Neofunctionalization is an adaptive mutation process; meaning one of the gene copies must mutate to develop a function that was not present in the ancestral gene. In other words, one of the duplicates retains its original function, while the other accumulates molecular changes such that, in time, it can perform a different task.

Constructive neutral evolution(CNE) is a theory that seeks to explain how complex systems can evolve through neutral transitions and spread through a population by chance fixation (genetic drift). Constructive neutral evolution is a competitor for both adaptationist explanations for the emergence of complex traits and hypotheses positing that a complex trait emerged as a response to a deleterious development in an organism. Constructive neutral evolution often leads to irreversible or "irremediable" complexity and produces systems which, instead of being finely adapted for performing a task, represent an excess complexity that has been described with terms such as "runaway bureaucracy" or even a "Rube Goldberg machine".

References

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  16. 1 2 Hughes AL (1999). Adaptive evolution of genes and genomes. New York: Oxford University Press. ISBN   978-0-19-511626-7.
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