INVESTIGADORES
FERNANDEZ Ariel
artículos
Título:
Subfunctionalization reduces the fitness cost of gene duplication in human by buffering dosage imbalances
Autor/es:
ARIEL FERNANDEZ; YUN-HUEI TZENG; SZE-BI HSU
Revista:
BMC GENOMICS
Editorial:
BIOMED CENTRAL LTD
Referencias:
Año: 2011 vol. 12 p. 604 - 604
ISSN:
1471-2164
Resumen:
Background: Driven essentially by random genetic drift, subfunctionalization has been identified as a possible
non-adaptive mechanism for the retention of duplicate genes in small-population species, where widespread
deleterious mutations are likely to cause complementary loss of subfunctions across gene copies. Through
subfunctionalization, duplicates become indispensable to maintain the functional requirements of the ancestral
locus. Yet, gene duplication produces a dosage imbalance in the encoded proteins and thus, as investigated in this
paper, subfunctionalization must be subject to the selective forces arising from the fitness bottleneck introduced
by the duplication event.Driven essentially by random genetic drift, subfunctionalization has been identified as a possible
non-adaptive mechanism for the retention of duplicate genes in small-population species, where widespread
deleterious mutations are likely to cause complementary loss of subfunctions across gene copies. Through
subfunctionalization, duplicates become indispensable to maintain the functional requirements of the ancestral
locus. Yet, gene duplication produces a dosage imbalance in the encoded proteins and thus, as investigated in this
paper, subfunctionalization must be subject to the selective forces arising from the fitness bottleneck introduced
by the duplication event.
Results: We show that, while arising from random drift, subfunctionalization must be inescapably subject to
selective forces, since the diversification of expression patterns across paralogs mitigates duplication-related dosage
imbalances in the concentrations of encoded proteins. Dosage imbalance effects become paramount when
proteins rely on obligatory associations to maintain their structural integrity, and are expected to be weaker when
protein complexation is ephemeral or adventitious. To establish the buffering effect of subfunctionalization on
selection pressure, we determine the packing quality of encoded proteins, an established indicator of dosage
sensitivity, and correlate this parameter with the extent of paralog segregation in humans, using species with larger
population -and more efficient selection- as controls.We show that, while arising from random drift, subfunctionalization must be inescapably subject to
selective forces, since the diversification of expression patterns across paralogs mitigates duplication-related dosage
imbalances in the concentrations of encoded proteins. Dosage imbalance effects become paramount when
proteins rely on obligatory associations to maintain their structural integrity, and are expected to be weaker when
protein complexation is ephemeral or adventitious. To establish the buffering effect of subfunctionalization on
selection pressure, we determine the packing quality of encoded proteins, an established indicator of dosage
sensitivity, and correlate this parameter with the extent of paralog segregation in humans, using species with larger
population -and more efficient selection- as controls.
Conclusions: Recognizing the role of subfunctionalization as a dosage-imbalance buffer in gene duplication events
enabled us to reconcile its mechanistic nonadaptive origin with its adaptive role as an enabler of the evolution of
genetic redundancy. This constructive role was established in this paper by proving the following assertion: If
subfunctionalization is indeed adaptive, its effect on paralog segregation should scale with the dosage sensitivity of the
duplicated genes. Thus, subfunctionalization becomes adaptive in response to the selection forces arising from the
fitness bottleneck imposed by gene duplication.Recognizing the role of subfunctionalization as a dosage-imbalance buffer in gene duplication events
enabled us to reconcile its mechanistic nonadaptive origin with its adaptive role as an enabler of the evolution of
genetic redundancy. This constructive role was established in this paper by proving the following assertion: If
subfunctionalization is indeed adaptive, its effect on paralog segregation should scale with the dosage sensitivity of the
duplicated genes. Thus, subfunctionalization becomes adaptive in response to the selection forces arising from the
fitness bottleneck imposed by gene duplication.If
subfunctionalization is indeed adaptive, its effect on paralog segregation should scale with the dosage sensitivity of the
duplicated genes. Thus, subfunctionalization becomes adaptive in response to the selection forces arising from the
fitness bottleneck imposed by gene duplication.. Thus, subfunctionalization becomes adaptive in response to the selection forces arising from the
fitness bottleneck imposed by gene duplication.