The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.

Diploid organisms contain a maternal and a paternal genome complement that is thought to provide robustness and allow developmental progression despite genetic perturbations that occur in heterozygosity. However, changes affecting gene dosage from the chromosome down to the individual gene level pos...

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Main Authors: M Felicia Basilicata, Claudia Isabelle Keller Valsecchi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-12-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009906&type=printable
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author M Felicia Basilicata
Claudia Isabelle Keller Valsecchi
author_facet M Felicia Basilicata
Claudia Isabelle Keller Valsecchi
author_sort M Felicia Basilicata
collection DOAJ
description Diploid organisms contain a maternal and a paternal genome complement that is thought to provide robustness and allow developmental progression despite genetic perturbations that occur in heterozygosity. However, changes affecting gene dosage from the chromosome down to the individual gene level possess a significant pathological potential and can lead to developmental disorders (DDs). This indicates that expression from a balanced gene complement is highly relevant for proper cellular and organismal function in eukaryotes. Paradoxically, gene and whole chromosome duplications are a principal driver of evolution, while heteromorphic sex chromosomes (XY and ZW) are naturally occurring aneuploidies important for sex determination. Here, we provide an overview of the biology of gene dosage at the crossroads between evolutionary benefit and pathogenicity during disease. We describe the buffering mechanisms and cellular responses to alterations, which could provide a common ground for the understanding of DDs caused by copy number alterations.
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publishDate 2021-12-01
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spelling doaj-art-e35d0ed3c4b14d6da2336a5885239b682025-08-20T03:15:43ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-12-011712e100990610.1371/journal.pgen.1009906The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.M Felicia BasilicataClaudia Isabelle Keller ValsecchiDiploid organisms contain a maternal and a paternal genome complement that is thought to provide robustness and allow developmental progression despite genetic perturbations that occur in heterozygosity. However, changes affecting gene dosage from the chromosome down to the individual gene level possess a significant pathological potential and can lead to developmental disorders (DDs). This indicates that expression from a balanced gene complement is highly relevant for proper cellular and organismal function in eukaryotes. Paradoxically, gene and whole chromosome duplications are a principal driver of evolution, while heteromorphic sex chromosomes (XY and ZW) are naturally occurring aneuploidies important for sex determination. Here, we provide an overview of the biology of gene dosage at the crossroads between evolutionary benefit and pathogenicity during disease. We describe the buffering mechanisms and cellular responses to alterations, which could provide a common ground for the understanding of DDs caused by copy number alterations.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009906&type=printable
spellingShingle M Felicia Basilicata
Claudia Isabelle Keller Valsecchi
The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.
PLoS Genetics
title The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.
title_full The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.
title_fullStr The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.
title_full_unstemmed The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.
title_short The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations.
title_sort good the bad and the ugly evolutionary and pathological aspects of gene dosage alterations
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1009906&type=printable
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