Protein Evolution Is Faster Outside the Cell

Julenius, Karin; Pedersen, Anders Gorm

doi:10.1093/molbev/msl081

Cited by 86 publications

(97 citation statements)

References 52 publications

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“…The analysis of the versatility of the old and young domains also showed that the young domains are the most versatile; with a versatility index twice that of other domain classes. The analysis of sub-cellular localization indicated that modern domains are mainly located in the proteins of extracellular regions and in extracellular segments of membrane proteins, consistent with previous studies showing that proteins in extracellular regions evolve faster than those of intracellular proteins (Julenius & Pedersen, 2006). Most old domains are located in the nucleus and cytoplasm.…”

Section: Discussionsupporting

confidence: 88%

Comparison of Exon-boundary Old and Young Domains during Metazoan Evolution

Lee¹

2009

Genomics & Informatics

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Domains are the building blocks of proteins. Exon shuffling is an important mechanism accounting for combination of a limited repertoire of protein domains in the evolution of multicellular species. A relative excess of domains encoded by symmetric exons in metazoan phyla has been presented as evidence of exon shuffling, and symmetric domains can be divided into old and new domains by determining the ages of the domains. In this report, we compare the spread, versatility, and subcellular localization of old and new domains by analyzing eight metazoan genomes and their respective annotated proteomes. We found that new domains have been expanding as multicellular organisms evolved, and this expansion was principally because of increases in class 1-1 domains amongst several classes of domain families. We also found that younger domains have been expanding in membranes and secreted proteins along with multi-cellular organism evolution. In contrast, old domains are located mainly in nuclear and cytoplasmic proteins. We conclude that the increasing mobility and versatility of new domains, in contrast to old domains, plays a significant role in metazoan evolution, facilitating the creation of secreted and transmembrane multidomain proteins unique to metazoa.

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Section: Discussionsupporting

confidence: 88%

Comparison of Exon-boundary Old and Young Domains during Metazoan Evolution

Lee¹

2009

Genomics & Informatics

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“…We built a phylogeny using the naive MSA, and we built two phylogenies each from the structural unmasked and masked MSAs. Previous work has shown that combined structural and functional constraints impose differing selection pressures in TM vs. extramembrane (EM) domains, in turn producing distinct amino-acid frequency distributions in each domain class (Tourasse and Li, 2000;Stevens and Arkin, 2001;Julenius and Pedersen, 2006;Oberai et al, 2009;Spielman and Wilke, 2013;Franzosa et al, 2013). As our structurally-curated MSAs allowed us to precisely identify each MSA column as either TM or EM, we were able to conduct far more rigorous phylogentic inference using a partitioned analysis.…”

Section: Structurally-aware Msa Strongly Improves Phylogenetic Inferencementioning

confidence: 99%

Comprehensive, structurally-curated alignment and phylogeny of vertebrate biogenic amine receptors

Spielman

Kumar

Wilke

2014

Preprint

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Biogenic amine receptors play critical roles in regulating behavior and physiology, particularly within the central nervous system, in both vertebrates and invertebrates. These receptors belong to the G-protein coupled receptor (GPCR) family and interact with endogenous bioamine ligands, such as dopamine, serotonin, and epinephrine, and they are targeted by a wide array of pharmaceuticals. Despite these receptors' clear clinical and biological importance, their evolutionary history remains poorly characterized. In particular, the relationships among biogenic amine receptors and any specific evolutionary constraints acting within distinct receptor subtypes are largely unknown. To advance and facilitate studies in this receptor family, we have constructed a comprehensive, high-quality, structurally-curated sequence alignment of vertebrate biogenic amine receptors. We demonstrate that aligning GPCR sequences without considering structure produces an alignment with substantial error, whereas a structurally-aware approach greatly improves alignment accuracy. Moreover, we show that phylogenetic inference with our structurally-curated alignment offers dramatic improvements over a structurally-naive alignment. Using the structural alignment and its corresponding phylogeny, we deduce novel biogenic amine receptor relationships and uncover previously unrecognized lineage-specific receptor clades. Moreover, we find that roughly 1% of the 3039 sequences in our final alignment are either misannotated or unclassified, and we propose updated classifications for these receptors. We release our comprehensive alignment and its corresponding phylogeny as a resource for future research into the evolution and diversification of biogenic amine receptors.

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“…An obvious sequence adaptation is the hydrophobic matching of the protein exterior, reflected in an apolar transmembrane amino acid composition. Although amino acid diversity is more limited in the transmembrane segments, simple compositional differences do not explain the slower divergence rates of transmembrane regions (1,4,5).…”

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confidence: 92%

“…disease mutation ͉ potassium channel ͉ protein folding ͉ protein stability ͉ single nucleotide polymorphisms E volutionary rates vary considerably in different cellular compartments (1). Membrane proteins have been found to diverge faster overall than soluble proteins (2,3), but this increased rate is confined entirely to the rapidly evolving extramembrane regions.…”

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confidence: 99%

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Structural imperatives impose diverse evolutionary constraints on helical membrane proteins

Oberai

Joh

Pettit

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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The amino acid sequences of transmembrane regions of helical membrane proteins are highly constrained, diverging at slower rates than their extramembrane regions and than water-soluble proteins. Moreover, helical membrane proteins seem to fall into fewer families than water-soluble proteins. The reason for the differential restrictions on sequence remains unexplained. Here, we show that the evolution of transmembrane regions is slowed by a previously unrecognized structural constraint: Transmembrane regions bury more residues than extramembrane regions and soluble proteins. This fundamental feature of membrane protein structure is an important contributor to the differences in evolutionary rate and to an increased susceptibility of the transmembrane regions to disease-causing single-nucleotide polymorphisms.disease mutation ͉ potassium channel ͉ protein folding ͉ protein stability ͉ single nucleotide polymorphisms E volutionary rates vary considerably in different cellular compartments (1). Membrane proteins have been found to diverge faster overall than soluble proteins (2, 3), but this increased rate is confined entirely to the rapidly evolving extramembrane regions. Transmembrane regions, on average, diverge much more slowly than the extramembrane regions more slowly than soluble proteins (1, 4-6).A major factor controlling protein sequence divergence is the need to preserve protein function by maintaining a folded structure (7). Because the physical forces that drive folding can change with environment, proteins in different cellular locations can be subject to distinct evolutionary constraints. Membrane proteins, in particular, must accommodate to a dramatically varied environment, ranging from hydrocarbon chains in the bilayer core to water as they emerge from the membrane (8, 9). It therefore seems possible that distinct structural imperatives found in different environments could be an important contributor to evolutionary rates. An obvious sequence adaptation is the hydrophobic matching of the protein exterior, reflected in an apolar transmembrane amino acid composition. Although amino acid diversity is more limited in the transmembrane segments, simple compositional differences do not explain the slower divergence rates of transmembrane regions (1, 4, 5).Here, we find that the transmembrane regions of membrane proteins bury more residues on average than soluble proteins and much more than extramembrane regions, a possible mechanism for increasing stabilization in the absence of the hydrophobic effect. Because buried residues evolve at slower rates than surface residues (10-12), the higher level of residue burial in the transmembrane regions leads to slower sequence divergence. Moreover, we find that higher residue burial may explain a higher prevalence of disease-causing mutations in the transmembrane region of membrane proteins compared with the extramembrane regions. Results and DiscussionTransmembrane Regions Bury More Residues. Fig. 1A shows plots of the fractional surface area buried per residue v...

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Protein Evolution Is Faster Outside the Cell

Cited by 86 publications

References 52 publications

Comparison of Exon-boundary Old and Young Domains during Metazoan Evolution

Comparison of Exon-boundary Old and Young Domains during Metazoan Evolution

Comprehensive, structurally-curated alignment and phylogeny of vertebrate biogenic amine receptors

Structural imperatives impose diverse evolutionary constraints on helical membrane proteins

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