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Testing the ortholog conjecture with comparative functional genomic data from mammals.

Nehrt NL, Clark WT, Radivojac P, Hahn MW - PLoS Comput. Biol. (2011)

Bottom Line: Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species.In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence.We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.

View Article: PubMed Central - PubMed

Affiliation: School of Informatics and Computing, Indiana University, Bloomington, Indiana, USA.

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The relationship between functional similarity and sequence identity for paralogs on the same chromosome (blue) and on different chromosomes (red).Standard error bars are shown. (A) Biological Process ontology, (B) Molecular Function ontology.
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pcbi-1002073-g003: The relationship between functional similarity and sequence identity for paralogs on the same chromosome (blue) and on different chromosomes (red).Standard error bars are shown. (A) Biological Process ontology, (B) Molecular Function ontology.

Mentions: It is known that paralogous sequences residing on the same chromosome are more likely to undergo non-allelic gene conversion in mammals [37], and are therefore more likely to maintain similar function due to concerted evolution. To explore this possibility, we examined the relationship between functional similarity and sequence identity for two types of gene duplication events: (i) those where the duplicated gene remains on the same chromosome (intrachromosomal), and (ii) those where the duplicated gene is moved to a different chromosome (interchromosomal). Figure 3 shows that a duplication event that places the new gene on a different chromosome reduces a protein's chances of retaining the original function. Interestingly, the extent of the functional divergence is statistically significant only in the Biological Process category, suggesting that while the biochemical function may be retained, the cellular context in which this function is utilized for a newly copied gene may be significantly different. Thus, gene transposition appears to be a viable evolutionary mechanism for mixing and matching protein molecular functions to attain more complex cellular functionalities.


Testing the ortholog conjecture with comparative functional genomic data from mammals.

Nehrt NL, Clark WT, Radivojac P, Hahn MW - PLoS Comput. Biol. (2011)

The relationship between functional similarity and sequence identity for paralogs on the same chromosome (blue) and on different chromosomes (red).Standard error bars are shown. (A) Biological Process ontology, (B) Molecular Function ontology.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3111532&req=5

pcbi-1002073-g003: The relationship between functional similarity and sequence identity for paralogs on the same chromosome (blue) and on different chromosomes (red).Standard error bars are shown. (A) Biological Process ontology, (B) Molecular Function ontology.
Mentions: It is known that paralogous sequences residing on the same chromosome are more likely to undergo non-allelic gene conversion in mammals [37], and are therefore more likely to maintain similar function due to concerted evolution. To explore this possibility, we examined the relationship between functional similarity and sequence identity for two types of gene duplication events: (i) those where the duplicated gene remains on the same chromosome (intrachromosomal), and (ii) those where the duplicated gene is moved to a different chromosome (interchromosomal). Figure 3 shows that a duplication event that places the new gene on a different chromosome reduces a protein's chances of retaining the original function. Interestingly, the extent of the functional divergence is statistically significant only in the Biological Process category, suggesting that while the biochemical function may be retained, the cellular context in which this function is utilized for a newly copied gene may be significantly different. Thus, gene transposition appears to be a viable evolutionary mechanism for mixing and matching protein molecular functions to attain more complex cellular functionalities.

Bottom Line: Among paralogs, those found within the same species are consistently more functionally similar than those found in a different species.In addition to offering implications for the computational prediction of protein function, our results shed light on the relationship between sequence divergence and functional divergence.We conclude that the most important factor in the evolution of function is not amino acid sequence, but rather the cellular context in which proteins act.

View Article: PubMed Central - PubMed

Affiliation: School of Informatics and Computing, Indiana University, Bloomington, Indiana, USA.

Show MeSH