NDLI: Evolutionary History and Functional Diversification of Phosphomannomutase Genes

Content Provider	Springer Nature Link
Author	Quental, Rita Moleirinho, Ana Azevedo, Luísa Amorim, António
Copyright Year	2010
Abstract	Phosphomannomutases (PMMs) catalyze the interconversion of mannose-6-phosphate to mannose-1-phosphate. In humans, two PMM enzymes exist—PMM1 and PMM2; yet, they have different functional specificities. PMM2 presents PMM activity, and its deficiency causes a Congenital Disorder of Glycosylation (PMM2-CDG). On the other hand, PMM1 can also act as glucose-1,6-bisphosphatase in the brain after stimulation with inosine monophosphate and thus far has not been implicated in any human disease. This study aims to refine the evolutionary time frame at which gene duplication gave rise to PMM1 and PMM2, and to identify the most likely amino acid positions underlying the proteins’ different functions. The phylogenetic analysis using available protein sequences, allowed us to establish that duplication occurred early in vertebrate evolution. In order to understand the molecular basis underlying the functional divergence, conserved and most likely functional divergence-related sites were identified, through the analysis of site-specific evolutionary rates. This analysis indicates that most of the sites known to be important in the homodimer formation and in the catalytic activity are conserved in both proteins. Among those potentially related to functional divergence, two positions (183 and 186 in human PMM1) emerge as the most interesting ones. The residues at these positions have different side-chain conformations in the protein structure in the unbound and bound states, and are highly but differently conserved in PMM1 and in PMM2 proteins. Altogether, these results provide new data into the evolutionary history of PMM1 and PMM2 duplicates and highlight the most probable sites that evolved to distinct functional specificities.
Starting Page	119
Ending Page	127
Page Count	9
File Format	PDF
ISSN	00222844
Journal	Journal of Molecular Evolution
Volume Number	71
Issue Number	2
e-ISSN	14321432
Language	English
Publisher	Springer-Verlag
Publisher Date	2010-07-27
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Phosphomannomutase Glucose-1,6-bisphosphatase CDG-Ia Functional divergence Gene duplication Phylogeny Rate shift Animal Genetics and Genomics Plant Genetics & Genomics Plant Sciences Microbiology Evolutionary Biology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Genetics Molecular Biology Ecology, Evolution, Behavior and Systematics

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