Limits...
Molecular trajectories leading to the alternative fates of duplicate genes.

Marotta M, Piontkivska H, Tanaka H - PLoS ONE (2012)

Bottom Line: The alternative fates are associated with expression divergence between these species, and reduced expression in humans is regulated by silencing mutations that have been propagated between duplicates by gene conversion.The difference in evolutionary processes left a unique DNA footprint in which dying duplicates are significantly more similar to each other (99.4%) than preserved ones.Such molecular trajectories could provide insights for the mechanisms underlying duplicate life and death in extant genomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.

ABSTRACT
Gene duplication generates extra gene copies in which mutations can accumulate without risking the function of pre-existing genes. Such mutations modify duplicates and contribute to evolutionary novelties. However, the vast majority of duplicates appear to be short-lived and experience duplicate silencing within a few million years. Little is known about the molecular mechanisms leading to these alternative fates. Here we delineate differing molecular trajectories of a relatively recent duplication event between humans and chimpanzees by investigating molecular properties of a single duplicate: DNA sequences, gene expression and promoter activities. The inverted duplication of the Glutathione S-transferase Theta 2 (GSTT2) gene had occurred at least 7 million years ago in the common ancestor of African great apes and is preserved in chimpanzees (Pan troglodytes), whereas a deletion polymorphism is prevalent in humans. The alternative fates are associated with expression divergence between these species, and reduced expression in humans is regulated by silencing mutations that have been propagated between duplicates by gene conversion. In contrast, selective constraint preserved duplicate divergence in chimpanzees. The difference in evolutionary processes left a unique DNA footprint in which dying duplicates are significantly more similar to each other (99.4%) than preserved ones. Such molecular trajectories could provide insights for the mechanisms underlying duplicate life and death in extant genomes.

Show MeSH
Molecular trajectories for the evolution of GSTT2 duplication.Purifying selection could have maintained the paralogous SNP site in chimpanzee. Under relaxed selection (for human duplication), gene conversion have homogenized duplicates, which resulted in (1) erasing the paralogous SNP and (2) transferring hypomorphic mutations.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3375281&req=5

pone-0038958-g006: Molecular trajectories for the evolution of GSTT2 duplication.Purifying selection could have maintained the paralogous SNP site in chimpanzee. Under relaxed selection (for human duplication), gene conversion have homogenized duplicates, which resulted in (1) erasing the paralogous SNP and (2) transferring hypomorphic mutations.

Mentions: In this study, we delineated evolutionary processes that differed between preserved and dying GSTT2 (Glutathione S-transferase Theta 2) duplicates, and elucidated important molecular events for each trajectory (Figure 6). First, we traced back the origin of tandem inverted GSTT2 duplication to the common ancestor of African great apes (Figure 1). The level of GSTT2 mRNA expression distinguishes dying duplicates (in humans) from preserved ones (in chimpanzees) (Figure 2). The mutations introducing premature stop codons are associated with a silenced duplicate (Figure 3), and regulatory mutations have been propagated between duplicates by gene conversion (Figure 4). In contrast, natural selection could be responsible for the preservation of duplicates and high-level expression in chimpanzees (Figure 5). These processes have left a paradoxical molecular footprint for duplicate evolution; DNA sequences are more similar to each other in dying duplicates than in preserved duplicates (Figure 5 and S6).


Molecular trajectories leading to the alternative fates of duplicate genes.

Marotta M, Piontkivska H, Tanaka H - PLoS ONE (2012)

Molecular trajectories for the evolution of GSTT2 duplication.Purifying selection could have maintained the paralogous SNP site in chimpanzee. Under relaxed selection (for human duplication), gene conversion have homogenized duplicates, which resulted in (1) erasing the paralogous SNP and (2) transferring hypomorphic mutations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375281&req=5

pone-0038958-g006: Molecular trajectories for the evolution of GSTT2 duplication.Purifying selection could have maintained the paralogous SNP site in chimpanzee. Under relaxed selection (for human duplication), gene conversion have homogenized duplicates, which resulted in (1) erasing the paralogous SNP and (2) transferring hypomorphic mutations.
Mentions: In this study, we delineated evolutionary processes that differed between preserved and dying GSTT2 (Glutathione S-transferase Theta 2) duplicates, and elucidated important molecular events for each trajectory (Figure 6). First, we traced back the origin of tandem inverted GSTT2 duplication to the common ancestor of African great apes (Figure 1). The level of GSTT2 mRNA expression distinguishes dying duplicates (in humans) from preserved ones (in chimpanzees) (Figure 2). The mutations introducing premature stop codons are associated with a silenced duplicate (Figure 3), and regulatory mutations have been propagated between duplicates by gene conversion (Figure 4). In contrast, natural selection could be responsible for the preservation of duplicates and high-level expression in chimpanzees (Figure 5). These processes have left a paradoxical molecular footprint for duplicate evolution; DNA sequences are more similar to each other in dying duplicates than in preserved duplicates (Figure 5 and S6).

Bottom Line: The alternative fates are associated with expression divergence between these species, and reduced expression in humans is regulated by silencing mutations that have been propagated between duplicates by gene conversion.The difference in evolutionary processes left a unique DNA footprint in which dying duplicates are significantly more similar to each other (99.4%) than preserved ones.Such molecular trajectories could provide insights for the mechanisms underlying duplicate life and death in extant genomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.

ABSTRACT
Gene duplication generates extra gene copies in which mutations can accumulate without risking the function of pre-existing genes. Such mutations modify duplicates and contribute to evolutionary novelties. However, the vast majority of duplicates appear to be short-lived and experience duplicate silencing within a few million years. Little is known about the molecular mechanisms leading to these alternative fates. Here we delineate differing molecular trajectories of a relatively recent duplication event between humans and chimpanzees by investigating molecular properties of a single duplicate: DNA sequences, gene expression and promoter activities. The inverted duplication of the Glutathione S-transferase Theta 2 (GSTT2) gene had occurred at least 7 million years ago in the common ancestor of African great apes and is preserved in chimpanzees (Pan troglodytes), whereas a deletion polymorphism is prevalent in humans. The alternative fates are associated with expression divergence between these species, and reduced expression in humans is regulated by silencing mutations that have been propagated between duplicates by gene conversion. In contrast, selective constraint preserved duplicate divergence in chimpanzees. The difference in evolutionary processes left a unique DNA footprint in which dying duplicates are significantly more similar to each other (99.4%) than preserved ones. Such molecular trajectories could provide insights for the mechanisms underlying duplicate life and death in extant genomes.

Show MeSH