The impact of the protein interactome on the syntenic structure of mammalian genomes.

Conserved synteny denotes evolutionary preserved gene order across species. It is not well understood to which degree functional relationships between genes are preserved in syntenic blocks. Here we investigate whether protein-coding genes conserved in mammalian syntenic blocks encode gene products...

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Main Authors: Isa Kristina Kirk, Nils Weinhold, Søren Brunak, Kirstine Belling
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0179112&type=printable
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author Isa Kristina Kirk
Nils Weinhold
Søren Brunak
Kirstine Belling
author_facet Isa Kristina Kirk
Nils Weinhold
Søren Brunak
Kirstine Belling
author_sort Isa Kristina Kirk
collection DOAJ
description Conserved synteny denotes evolutionary preserved gene order across species. It is not well understood to which degree functional relationships between genes are preserved in syntenic blocks. Here we investigate whether protein-coding genes conserved in mammalian syntenic blocks encode gene products that serve the common functional purpose of interacting at protein level, i.e. connectivity. High connectivity among protein-protein interactions (PPIs) was only moderately associated with conserved synteny on a genome-wide scale. However, we observed a smaller subset of 3.6% of all syntenic blocks with high-confidence PPIs that had significantly higher connectivity than expected by random. Additionally, syntenic blocks with high-confidence PPIs contained significantly more chromatin loops than the remaining blocks, indicating functional preservation among these syntenic blocks. Conserved synteny is typically defined by sequence similarity. In this study, we also examined whether a functional relationship, here PPI connectivity, can identify syntenic blocks independently of orthology. While orthology-based syntenic blocks with high-confident PPIs and the connectivity-based syntenic blocks largely overlapped, the connectivity-based approach identified additional syntenic blocks that were not found by conventional sequence-based methods alone. Additionally, the connectivity-based approach enabled identification of potential orthologous genes between species. Our analyses demonstrate that subsets of syntenic blocks are associated with highly connected proteins, and that PPI connectivity can be used to detect conserved synteny even if sequence conservation drifts beyond what orthology algorithms normally can identify.
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spelling doaj-art-2f3295abb8414465ad32ddebd8d707222025-08-20T02:03:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e017911210.1371/journal.pone.0179112The impact of the protein interactome on the syntenic structure of mammalian genomes.Isa Kristina KirkNils WeinholdSøren BrunakKirstine BellingConserved synteny denotes evolutionary preserved gene order across species. It is not well understood to which degree functional relationships between genes are preserved in syntenic blocks. Here we investigate whether protein-coding genes conserved in mammalian syntenic blocks encode gene products that serve the common functional purpose of interacting at protein level, i.e. connectivity. High connectivity among protein-protein interactions (PPIs) was only moderately associated with conserved synteny on a genome-wide scale. However, we observed a smaller subset of 3.6% of all syntenic blocks with high-confidence PPIs that had significantly higher connectivity than expected by random. Additionally, syntenic blocks with high-confidence PPIs contained significantly more chromatin loops than the remaining blocks, indicating functional preservation among these syntenic blocks. Conserved synteny is typically defined by sequence similarity. In this study, we also examined whether a functional relationship, here PPI connectivity, can identify syntenic blocks independently of orthology. While orthology-based syntenic blocks with high-confident PPIs and the connectivity-based syntenic blocks largely overlapped, the connectivity-based approach identified additional syntenic blocks that were not found by conventional sequence-based methods alone. Additionally, the connectivity-based approach enabled identification of potential orthologous genes between species. Our analyses demonstrate that subsets of syntenic blocks are associated with highly connected proteins, and that PPI connectivity can be used to detect conserved synteny even if sequence conservation drifts beyond what orthology algorithms normally can identify.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0179112&type=printable
spellingShingle Isa Kristina Kirk
Nils Weinhold
Søren Brunak
Kirstine Belling
The impact of the protein interactome on the syntenic structure of mammalian genomes.
PLoS ONE
title The impact of the protein interactome on the syntenic structure of mammalian genomes.
title_full The impact of the protein interactome on the syntenic structure of mammalian genomes.
title_fullStr The impact of the protein interactome on the syntenic structure of mammalian genomes.
title_full_unstemmed The impact of the protein interactome on the syntenic structure of mammalian genomes.
title_short The impact of the protein interactome on the syntenic structure of mammalian genomes.
title_sort impact of the protein interactome on the syntenic structure of mammalian genomes
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0179112&type=printable
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