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Group 5 Name of group:Humus and Pitta Group secretary plus email:Philip Sentongo(bt09263@qmul.ac.uk) Group members plus email:Jessica Jayne Guy ([|bt09122@qmul.ac.uk] ) Sara AL-Zubeidi (bt09337@qmul.ac.uk) Jamie Parker (bt09208@qmul.ac.uk) Philip Sentongo (bt09263@qmul.ac.uk) Haroun Hickman (bt09056@qmul.ac.uk)

What is the evolutionary fate of duplicated genes (max 1000 words) excluding references

**__The evolutionary fate of duplicated genes.__** Duplication is a very important process in evolution, as once a gene is duplicated; generally one of the two can mutate, and diverge from the other, which can result in two different genes with different functions. By definition, duplication is ‘a chromosome aberration in which a chromosomes segment is present more than once in the haploid genome.’ It has been found that the new genes are formed from prexisiting ones, and that its new functions evolve from prexisiting gene functions.

There are two main types of gene duplication that are focused on in terms of evolution; these are orthologous genes and paralogous genes. Orthologous genes are present in many species that are closely related and all these genes descend from a gene that is present in a common ancestor. They retain the same function, and are only duplicated as ‘an accompaniment to speciation.’(Hart et al 2005). Paralogous genes are multiple genes that come from a gene from a common ancestor through one or many duplications, after which sequence divergence occurs. After gene duplication, the paralogs are inactive, and one in able to evolve in any way. It has been found that the most common occurrence is that one of the paralogs undergoes a mutation that stops it form functioning as it did before. It can also be deleted. However, sometimes, a paralog can undergo mutations that cause it not to be destroyed, but instead causes the paralogs to diverge, by changing the function of one paralogs, so it’s different to the original gene.

. ....You should celarly say where this figure comes from and the figure needs explanation in the text These gene duplications can also give rise to specialization of genes. This can occur by a gene duplication of a gene being expressed in two tissue types for example. After duplication, the two paralogs can undergo different mutation, which could occur in the enhancer elements, resulting in one gene now only expressing in one tissue type, and the one only expressing in the other tissue type. This is known as subfunctionalization. Often, gene duplications are a result of meiotic recombination occurring between homologous segments or portions of DNA that are either very similar in sequence, or identical. Some times, this recombination can occur between two very short matching sequences of DNA sequences, one occurring either side of a gene. After recombination, this produces one chromosome with two copies of the gene in question, and one short chromosome. Once the process of unequal crossing over has occurred, more unequal crossing over can occur, adding more copied of the gene to the chromosome containing two copies of the gene.

An example of how successive duplication of genes over time can contribute to the evolution of organisms is the Globin Gene Family.
 * Duplication example, Globin Gene family **

The most primitive oxygen-carrying protein is a globin polypeptide chain of 150 amino acids, found in marine worms and primitive fish. Haemoglobin and Myoglobin are part of the Globin Gene Family. They originate from the same ancestrol globin gene. After duplication of the ancestrol globin gene, it created myoglobin and haemoglobin, both similar in shape and function but specialised to operate in diffferent tissues. For Haemoglobin, the ancestrol globin gene also gave rise to the following genes by succesive duplication: Alpha, Beta, Gamma, Epsilon and Zeta. (α,ß,γ,ε,ζ) These genes are specialised for different stages in the development from foetus to adult. Each globin is made in different amounts at different times of human development.



During the evolution of mammals, the ß globin gene underwent duplication and mutation to give rise to a second ß- like chain that is made for the foetus which subseuqently has a higher affinity than an adult for oxygen and helps with the transfer of oxygen from mother to foetus.

The gene for the new ß -like chain subsequently mutated and duplicated again to produce two new genes, ε and the γ, ε chain being produced earlier in development than the foetal γ chain. The gene duplication of the adult beta chain gene again took place during primate evolution to give rise to σ globin gene and thus a minor form of haemoglobin found only in adult primates. The ancestrol α globin also duplicated to give rise to modern α globin and ζ. At each stage of developemt ....spelling, the heamoglobin tetramer consists of two α-type and two ß-type chains. The ε and ζ chains appear in early embryos which are then replaced by γ and α chains in the foetus, giving (α2 γ2) haemoglobin which has a better affinity for oxygen than adult haemoglobin (α2 ß2)



There are evolutionary forces influencing gene duplicability, one explanation for this is the dosage imbalance hypothesis. This states that the imbalance of the components of a protein complex can be deleterious. If a dosage imbalance is deleterious the survivability of a duplicated gene is determined by the dosage effect. This was later extended to include the fact that protein under-wrapping ....means what? has an effect on dosage imbalances, decreasing gene duplicability. This is because under-wrapped proteins have a higher chance of having their intramolecular hydrogen bonds attacked ....by what? , when not stabilised by interactions with other proteins, forming aberrant misfolding and aggregation through overexpression which causes dosage sensitivity.

In yeast under-wrapping was consistently more under-wrapped in singletons than duplicated genes in different functional categories. As complexity increases, especially in higher eukaryotes, under-wrapping becomes less important to the dosage effect this is due to several factors: · Alternative splicing which can be used to avoid imbalances · More efficient control of expression, i.e. non-coding RNAs and chaperons · Many can interact with similar or the same proteins removing themselves, stopping imbalances · Since complex organisms have considerably smaller populations a slightly deleterious dosage imbalance due to duplication have a higher chance of being fixed in the population · Functional diversification may have led to retention of the duplicated genes, i.e. the major histocompatability complex, MHC, in mammals.

When whole genome duplications occur there is little or no dosage imbalance. Whole genome duplication (WGD) followed by massive gene loss and speciation is a powerful source of functional innovation. One example of this is S.//cerevisae// who’s ancestor underwent an ancient WGD when compared to K.//waltii// a related species that diverged before the duplication event it was found that one region on K.//waltii// corresponded to two regions on S.//cerevisae//. it was found that although the WGD doubled the amount of DNA S.//cerevisae// underwent subsequent small gene loss equally between the sister regions resulting in a genome that is only 13% larger and 10% more genes than K.//waltii//. After the WGD it was found that in 95% of cases accelerated evolution only occurred in one (the derived) paralogue. While one kept its ancestral function, the other was free to evolve more rapidly and develop a new function i.e. CET1 is a mRNA capping enzyme beta subunit (80kDa) is a slowly evolving ancestral gene its paralogue is a rapidly evolving derived function CTL1 a RNA triphophatase with no capping function. Ancestral and derived paralogues are distinct from each other and recognised by the using mutants with deletions, in 18% of cases deletion of the ancestral paralogue was lethal when grown in a rich medium. Whereas in derived paralogues no mutants with such deletions were ever lethal. This shows that the derived functions are not essential in such conditions and compliment the ancestral genes. It also showed that in many cases on gaining a new function the derived paralogue has lost its ancestral function.

· Alberts .B. //et al.// (2004). Essential cell biology, 2nd edition. Chapter 9 – //‘how genes and genomes evolve.’// New York, Garland Publishing. 297-301.  · Lodish H.F. //et al// (2000). Molecular cell biology, 4th edition. Chapter 9.2 – //‘chromosomal organization of genes and non coding DNA.’// New York, W. H. Freeman. · Hartl, D.L, Jones, E.W. (2005) Genetics – Analysis of gene and genomes, 6th edition. Chapter 17.1 – ‘//molecular evolution.’// Massachusetts, Jones and Bartlett publishing. 724-725.  · Clark. P.D, (2005). Molecular biology – understanding the genetic revolution. Chapter 20 – ‘//Molecular evolution.’// Oxford, Elsevire academic press.
 * __References:__**

Kellis M, Birren BW, Lander ES, 2004. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature. 428(6983),pp617-24 Liang H, Plazonic KR, Chen J, Li WH, Fernández A, 2007. Protein under-wrapping causes dosage sensitivity and decreases gene duplicability. PLoS Genet. 4(1):e11 ....excellent