Evidence map›Paper›PMID 29858274›Full record

ArticleGenome research2018

Human long intrinsically disordered protein regions are frequent targets of positive selection.

Arina Afanasyeva, Mathias Bockwoldt, Christopher R Cooney, Ines Heiland, Toni I Gossmann

Abstract read
In one paragraph

Article in Genome research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Arina Afanasyeva *Department of Animal and Plant Sciences, University of Sheffield, Sheffield S102TN, United Kingdom.
Mathias Bockwoldt *Department of Arctic and Marine Biology, UiT The Arctic University of Norway, 9037 Tromsø, Norway.
Christopher R CooneyDepartment of Animal and Plant Sciences, University of Sheffield, Sheffield S102TN, United Kingdom.
Ines HeilandDepartment of Arctic and Marine Biology, UiT The Arctic University of Norway, 9037 Tromsø, Norway.
Toni I GossmannDepartment of Animal and Plant Sciences, University of Sheffield, Sheffield S102TN, United Kingdom.ORCID 0000-0001-6609-4116

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intrinsically disordered regions occur frequently in proteins and are characterized by a lack of a well-defined three-dimensional structure. Although these regions do not show a higher order of structural organization, they are known to be functionally important. Disordered regions are rapidly evolving, largely attributed to relaxed purifying selection and an increased role of genetic drift. It has also been suggested that positive selection might contribute to their rapid diversification. However, for our own species, it is currently unknown whether positive selection has played a role during the evolution of these protein regions. Here, we address this question by investigating the evolutionary pattern of more than 6600 human proteins with intrinsically disordered regions and their ordered counterparts. Our comparative approach with data from more than 90 mammalian genomes uses a priori knowledge of disordered protein regions, and we show that this increases the power to detect positive selection by an order of magnitude. We can confirm that human intrinsically disordered regions evolve more rapidly, not only within humans but also across the entire mammalian phylogeny. They have, however, experienced substantial evolutionary constraint, hinting at their fundamental functional importance. We find compelling evidence that disordered protein regions are frequent targets of positive selection and estimate that the relative rate of adaptive substitutions differs fourfold between disordered and ordered protein regions in humans. Our results suggest that disordered protein regions are important targets of genetic innovation and that the contribution of positive selection in these regions is more pronounced than in other protein parts.

Indexed as

AnimalsEvolution, MolecularGenomeHumansIntrinsically Disordered ProteinsMammalsProtein DomainsSelection, GeneticIntrinsically Disordered Proteins

Identifiers

PMID29858274
PMCPMC6028134

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.