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Coordinated genome-wide modifications within proximal promoter cis-regulatory elements during vertebrate evolution.

Yokoyama KD, Thorne JL, Wray GA - Genome Biol Evol (2010)

Bottom Line: Focusing on regulatory motifs overrepresented at specific locations within or near the promoter, we find that a surprisingly large number of cis-regulatory elements have been subject to coordinated genome-wide modifications during vertebrate evolution, such that the motif frequency changes on a single branch of vertebrate phylogeny.Many of these modifications are likely to be compensatory changes throughout the genome following changes in protein factor binding affinities, whereas others may be due to changes in mutation rates or effective population size.The likelihood that this happened many times during vertebrate evolution highlights the need to examine additional taxa and to understand the evolutionary and molecular mechanisms underlying the evolution of protein-DNA interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University, USA. ken.yokoyama@ucdenver.edu

ABSTRACT
There often exists a "one-to-many" relationship between a transcription factor and a multitude of binding sites throughout the genome. It is commonly assumed that transcription factor binding motifs remain largely static over the course of evolution because changes in binding specificity can alter the interactions with potentially hundreds of sites across the genome. Focusing on regulatory motifs overrepresented at specific locations within or near the promoter, we find that a surprisingly large number of cis-regulatory elements have been subject to coordinated genome-wide modifications during vertebrate evolution, such that the motif frequency changes on a single branch of vertebrate phylogeny. This was found to be the case even between closely related mammal species, with nearly a third of all location-specific consensus motifs exhibiting significant modifications within the human or mouse lineage since their divergence. Many of these modifications are likely to be compensatory changes throughout the genome following changes in protein factor binding affinities, whereas others may be due to changes in mutation rates or effective population size. The likelihood that this happened many times during vertebrate evolution highlights the need to examine additional taxa and to understand the evolutionary and molecular mechanisms underlying the evolution of protein-DNA interactions.

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Prevalence of evolutionary modifications within location-specific consensus motifs according to divergence time. y axis values represent the fraction of regulatory consensus motifs exhibiting evolutionary changes in sequence following species divergence (Z-score > 5). Species comparisons were conducted in a pairwise fashion, each comparison producing a single set of modified motifs. The sets of modified motifs are separated according to divergence time between the corresponding pair of species (x axis) (Hedges et al. 2006). Each barplot shows the median fraction of modified consensus motifs (center line), the first and third quartile (bar extremes), and the most extreme comparisons within 80% of the interquartile range (standard bar). Circles represent single outlier points.
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fig4: Prevalence of evolutionary modifications within location-specific consensus motifs according to divergence time. y axis values represent the fraction of regulatory consensus motifs exhibiting evolutionary changes in sequence following species divergence (Z-score > 5). Species comparisons were conducted in a pairwise fashion, each comparison producing a single set of modified motifs. The sets of modified motifs are separated according to divergence time between the corresponding pair of species (x axis) (Hedges et al. 2006). Each barplot shows the median fraction of modified consensus motifs (center line), the first and third quartile (bar extremes), and the most extreme comparisons within 80% of the interquartile range (standard bar). Circles represent single outlier points.

Mentions: Using this approach, we conducted pairwise comparisons across an array of eight mammalian lineages (supplementary table 1, Supplementary Material online). We found that a large fraction of location-specific regulatory motifs have been subject to evolutionary changes in consensus sequence. For instance, we find that close to a third of all location-specific consensus motifs have been modified on either the human or mouse lineages following their divergence (Z > 5) (supplementary tables 2 & 3, Supplementary Material online). Comparisons between other species with divergence times similar to that of human and mouse (Hedges et al. 2006) produced similar numbers of modified consensus sequences, with predicted modifications generally occurring within 24–35% of all location-specific consensus motifs (fig. 4). There was also a strong correlation between divergence time and the prevalence of consensus sequence modification. Only 6% of all consensus motifs exhibited differences within primates, at divergence times less than 30 My (Hedges et al. 2006). In contrast, about half of all location-specific consensus motifs exhibited differences between eutherians and the more distantly related possum lineage (divergence times of 160 My [Hedges et al. 2006]).


Coordinated genome-wide modifications within proximal promoter cis-regulatory elements during vertebrate evolution.

Yokoyama KD, Thorne JL, Wray GA - Genome Biol Evol (2010)

Prevalence of evolutionary modifications within location-specific consensus motifs according to divergence time. y axis values represent the fraction of regulatory consensus motifs exhibiting evolutionary changes in sequence following species divergence (Z-score > 5). Species comparisons were conducted in a pairwise fashion, each comparison producing a single set of modified motifs. The sets of modified motifs are separated according to divergence time between the corresponding pair of species (x axis) (Hedges et al. 2006). Each barplot shows the median fraction of modified consensus motifs (center line), the first and third quartile (bar extremes), and the most extreme comparisons within 80% of the interquartile range (standard bar). Circles represent single outlier points.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3021792&req=5

fig4: Prevalence of evolutionary modifications within location-specific consensus motifs according to divergence time. y axis values represent the fraction of regulatory consensus motifs exhibiting evolutionary changes in sequence following species divergence (Z-score > 5). Species comparisons were conducted in a pairwise fashion, each comparison producing a single set of modified motifs. The sets of modified motifs are separated according to divergence time between the corresponding pair of species (x axis) (Hedges et al. 2006). Each barplot shows the median fraction of modified consensus motifs (center line), the first and third quartile (bar extremes), and the most extreme comparisons within 80% of the interquartile range (standard bar). Circles represent single outlier points.
Mentions: Using this approach, we conducted pairwise comparisons across an array of eight mammalian lineages (supplementary table 1, Supplementary Material online). We found that a large fraction of location-specific regulatory motifs have been subject to evolutionary changes in consensus sequence. For instance, we find that close to a third of all location-specific consensus motifs have been modified on either the human or mouse lineages following their divergence (Z > 5) (supplementary tables 2 & 3, Supplementary Material online). Comparisons between other species with divergence times similar to that of human and mouse (Hedges et al. 2006) produced similar numbers of modified consensus sequences, with predicted modifications generally occurring within 24–35% of all location-specific consensus motifs (fig. 4). There was also a strong correlation between divergence time and the prevalence of consensus sequence modification. Only 6% of all consensus motifs exhibited differences within primates, at divergence times less than 30 My (Hedges et al. 2006). In contrast, about half of all location-specific consensus motifs exhibited differences between eutherians and the more distantly related possum lineage (divergence times of 160 My [Hedges et al. 2006]).

Bottom Line: Focusing on regulatory motifs overrepresented at specific locations within or near the promoter, we find that a surprisingly large number of cis-regulatory elements have been subject to coordinated genome-wide modifications during vertebrate evolution, such that the motif frequency changes on a single branch of vertebrate phylogeny.Many of these modifications are likely to be compensatory changes throughout the genome following changes in protein factor binding affinities, whereas others may be due to changes in mutation rates or effective population size.The likelihood that this happened many times during vertebrate evolution highlights the need to examine additional taxa and to understand the evolutionary and molecular mechanisms underlying the evolution of protein-DNA interactions.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Duke University, USA. ken.yokoyama@ucdenver.edu

ABSTRACT
There often exists a "one-to-many" relationship between a transcription factor and a multitude of binding sites throughout the genome. It is commonly assumed that transcription factor binding motifs remain largely static over the course of evolution because changes in binding specificity can alter the interactions with potentially hundreds of sites across the genome. Focusing on regulatory motifs overrepresented at specific locations within or near the promoter, we find that a surprisingly large number of cis-regulatory elements have been subject to coordinated genome-wide modifications during vertebrate evolution, such that the motif frequency changes on a single branch of vertebrate phylogeny. This was found to be the case even between closely related mammal species, with nearly a third of all location-specific consensus motifs exhibiting significant modifications within the human or mouse lineage since their divergence. Many of these modifications are likely to be compensatory changes throughout the genome following changes in protein factor binding affinities, whereas others may be due to changes in mutation rates or effective population size. The likelihood that this happened many times during vertebrate evolution highlights the need to examine additional taxa and to understand the evolutionary and molecular mechanisms underlying the evolution of protein-DNA interactions.

Show MeSH