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Network analysis of metabolic enzyme evolution in Escherichia coli.

Light S, Kraulis P - BMC Bioinformatics (2004)

Bottom Line: In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model.However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs.Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

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Affiliation: Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm Center for Physics, Astronomy and Biotechnology, Stockholm University, Stockholm SE-10691, Sweden. sara@sbc.su.se

ABSTRACT

Background: The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc.

Results: Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL) between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1.

Conclusions: The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

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Homology vs minimal path length (MPL) without the 20 most promiscuous compounds for functionally similar enzyme pairs. The plots show the correlation between homology and MPL for functionally similar (shared primary EC number) enzyme pairs when the 20 most promiscuous compounds have been removed. The solid line represents the metabolic network of E. coli. The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.
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Figure 9: Homology vs minimal path length (MPL) without the 20 most promiscuous compounds for functionally similar enzyme pairs. The plots show the correlation between homology and MPL for functionally similar (shared primary EC number) enzyme pairs when the 20 most promiscuous compounds have been removed. The solid line represents the metabolic network of E. coli. The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.

Mentions: The functionally similar, dissimilar and undetermined homologous enzyme pairs were plotted against MPL and normalized against 1,000 randomized networks by the same method as described above. From this procedure we could determine that most of the correlation between homology and MPL at MPL 1 can be attributed to enzymes with similar functions (Figure 9) and enzymes with undetermined function (data not shown). However, there is still an over-representation of functionally dissimilar homologous enzyme pairs at MPL 1 (Figure 10) indicating that there is a statistically significant proportion of the homologous enzyme pairs whose homology cannot be attributed to chemical similarity. We also note an over-representation at MPL 10 for the functionally similar homologous pairs (Figure 9). The over-representation consists of 9 pairs of homologous inner membrane MFS transporters which show 15–20% sequence identity.


Network analysis of metabolic enzyme evolution in Escherichia coli.

Light S, Kraulis P - BMC Bioinformatics (2004)

Homology vs minimal path length (MPL) without the 20 most promiscuous compounds for functionally similar enzyme pairs. The plots show the correlation between homology and MPL for functionally similar (shared primary EC number) enzyme pairs when the 20 most promiscuous compounds have been removed. The solid line represents the metabolic network of E. coli. The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.
© Copyright Policy
Related In: Results  -  Collection

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Figure 9: Homology vs minimal path length (MPL) without the 20 most promiscuous compounds for functionally similar enzyme pairs. The plots show the correlation between homology and MPL for functionally similar (shared primary EC number) enzyme pairs when the 20 most promiscuous compounds have been removed. The solid line represents the metabolic network of E. coli. The dotted vertical lines represent three standard deviations of the number of homologous enzyme pairs for the randomized networks. The number of homologous enzyme pairs has been normalized by the average number of homologous enzyme pairs for the randomized networks.
Mentions: The functionally similar, dissimilar and undetermined homologous enzyme pairs were plotted against MPL and normalized against 1,000 randomized networks by the same method as described above. From this procedure we could determine that most of the correlation between homology and MPL at MPL 1 can be attributed to enzymes with similar functions (Figure 9) and enzymes with undetermined function (data not shown). However, there is still an over-representation of functionally dissimilar homologous enzyme pairs at MPL 1 (Figure 10) indicating that there is a statistically significant proportion of the homologous enzyme pairs whose homology cannot be attributed to chemical similarity. We also note an over-representation at MPL 10 for the functionally similar homologous pairs (Figure 9). The over-representation consists of 9 pairs of homologous inner membrane MFS transporters which show 15–20% sequence identity.

Bottom Line: In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model.However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs.Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

View Article: PubMed Central - HTML - PubMed

Affiliation: Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm Center for Physics, Astronomy and Biotechnology, Stockholm University, Stockholm SE-10691, Sweden. sara@sbc.su.se

ABSTRACT

Background: The two most common models for the evolution of metabolism are the patchwork evolution model, where enzymes are thought to diverge from broad to narrow substrate specificity, and the retrograde evolution model, according to which enzymes evolve in response to substrate depletion. Analysis of the distribution of homologous enzyme pairs in the metabolic network can shed light on the respective importance of the two models. We here investigate the evolution of the metabolism in E. coli viewed as a single network using EcoCyc.

Results: Sequence comparison between all enzyme pairs was performed and the minimal path length (MPL) between all enzyme pairs was determined. We find a strong over-representation of homologous enzymes at MPL 1. We show that the functionally similar and functionally undetermined enzyme pairs are responsible for most of the over-representation of homologous enzyme pairs at MPL 1.

Conclusions: The retrograde evolution model predicts that homologous enzymes pairs are at short metabolic distances from each other. In general agreement with previous studies we find that homologous enzymes occur close to each other in the network more often than expected by chance, which lends some support to the retrograde evolution model. However, we show that the homologous enzyme pairs which may have evolved through retrograde evolution, namely the pairs that are functionally dissimilar, show a weaker over-representation at MPL 1 than the functionally similar enzyme pairs. Our study indicates that, while the retrograde evolution model may have played a small part, the patchwork evolution model is the predominant process of metabolic enzyme evolution.

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