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Developmental constraints on vertebrate genome evolution.

Roux J, Robinson-Rechavi M - PLoS Genet. (2008)

Bottom Line: We show that, in both species, genes expressed early in development (1) have a more dramatic effect of knock-out or mutation and (2) are more likely to revert to single copy after whole genome duplication, relative to genes expressed late.We determine the pattern of these constraints, which differs from the model used to describe vertebrate morphological conservation ("hourglass" model).While morphological constraints reach a maximum at mid-development (the "phylotypic" stage), genomic constraints appear to decrease in a monotonous manner over developmental time.

View Article: PubMed Central - PubMed

Affiliation: Université de Lausanne, Département d'Ecologie et d'Evolution, Quartier Sorge, Lausanne, Switzerland.

ABSTRACT
Constraints in embryonic development are thought to bias the direction of evolution by making some changes less likely, and others more likely, depending on their consequences on ontogeny. Here, we characterize the constraints acting on genome evolution in vertebrates. We used gene expression data from two vertebrates: zebrafish, using a microarray experiment spanning 14 stages of development, and mouse, using EST counts for 26 stages of development. We show that, in both species, genes expressed early in development (1) have a more dramatic effect of knock-out or mutation and (2) are more likely to revert to single copy after whole genome duplication, relative to genes expressed late. This supports high constraints on early stages of vertebrate development, making them less open to innovations (gene gain or gene loss). Results are robust to different sources of data -- gene expression from microarrays, ESTs, or in situ hybridizations; and mutants from directed KO, transgenic insertions, point mutations, or morpholinos. We determine the pattern of these constraints, which differs from the model used to describe vertebrate morphological conservation ("hourglass" model). While morphological constraints reach a maximum at mid-development (the "phylotypic" stage), genomic constraints appear to decrease in a monotonous manner over developmental time.

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Expression in zebrafish development of essential genes.(A) Median expression profiles of zebrafish essential genes, in red dashed line and triangles, compared to non-annotated genes in black solid line and circles. (B) Significance of the expression difference between the two groups of genes. 1‰ and 1% confidence intervals are drawn in dashed lines. Significant points (outside the 1% confidence interval) are filled on both plots. A Spearman correlation was computed (coefficient ρ) to test the trend over time. The x-axis is in logarithmic scale. A gray box on the x-axis indicates the phylotypic period.
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pgen-1000311-g002: Expression in zebrafish development of essential genes.(A) Median expression profiles of zebrafish essential genes, in red dashed line and triangles, compared to non-annotated genes in black solid line and circles. (B) Significance of the expression difference between the two groups of genes. 1‰ and 1% confidence intervals are drawn in dashed lines. Significant points (outside the 1% confidence interval) are filled on both plots. A Spearman correlation was computed (coefficient ρ) to test the trend over time. The x-axis is in logarithmic scale. A gray box on the x-axis indicates the phylotypic period.

Mentions: Considering gene expression either “present” or “absent” allows straightforward statistical analysis, but it is a strong approximation of the continuous nature of gene expression. To take advantage of the quantitative signal from the microarray data, we contrasted the median expression level of all the essential genes to that of all of the reference genes (Figure 2A). We used the median because it is less sensitive to extreme values [18]; results were consistent using the mean (not shown). To estimate the significance of the difference between the two curves, we performed a randomization test (see Methods), which provides 1% and 1‰ confidence intervals (Figure 2B). The expectation is now that the essential genes should be enriched in genes highly expressed at the stages with strong constraints. And consistently with the previous observations, essential genes are significantly more expressed in early stages (until 11.7 hours), and less expressed in late stages of development (from 5 days to 14 days). No specific trend is visible around the phylotypic stage. Similar results are obtained for genes which give an “abnormal” phenotype after loss of function (Text S1 and Figure S4).


Developmental constraints on vertebrate genome evolution.

Roux J, Robinson-Rechavi M - PLoS Genet. (2008)

Expression in zebrafish development of essential genes.(A) Median expression profiles of zebrafish essential genes, in red dashed line and triangles, compared to non-annotated genes in black solid line and circles. (B) Significance of the expression difference between the two groups of genes. 1‰ and 1% confidence intervals are drawn in dashed lines. Significant points (outside the 1% confidence interval) are filled on both plots. A Spearman correlation was computed (coefficient ρ) to test the trend over time. The x-axis is in logarithmic scale. A gray box on the x-axis indicates the phylotypic period.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600815&req=5

pgen-1000311-g002: Expression in zebrafish development of essential genes.(A) Median expression profiles of zebrafish essential genes, in red dashed line and triangles, compared to non-annotated genes in black solid line and circles. (B) Significance of the expression difference between the two groups of genes. 1‰ and 1% confidence intervals are drawn in dashed lines. Significant points (outside the 1% confidence interval) are filled on both plots. A Spearman correlation was computed (coefficient ρ) to test the trend over time. The x-axis is in logarithmic scale. A gray box on the x-axis indicates the phylotypic period.
Mentions: Considering gene expression either “present” or “absent” allows straightforward statistical analysis, but it is a strong approximation of the continuous nature of gene expression. To take advantage of the quantitative signal from the microarray data, we contrasted the median expression level of all the essential genes to that of all of the reference genes (Figure 2A). We used the median because it is less sensitive to extreme values [18]; results were consistent using the mean (not shown). To estimate the significance of the difference between the two curves, we performed a randomization test (see Methods), which provides 1% and 1‰ confidence intervals (Figure 2B). The expectation is now that the essential genes should be enriched in genes highly expressed at the stages with strong constraints. And consistently with the previous observations, essential genes are significantly more expressed in early stages (until 11.7 hours), and less expressed in late stages of development (from 5 days to 14 days). No specific trend is visible around the phylotypic stage. Similar results are obtained for genes which give an “abnormal” phenotype after loss of function (Text S1 and Figure S4).

Bottom Line: We show that, in both species, genes expressed early in development (1) have a more dramatic effect of knock-out or mutation and (2) are more likely to revert to single copy after whole genome duplication, relative to genes expressed late.We determine the pattern of these constraints, which differs from the model used to describe vertebrate morphological conservation ("hourglass" model).While morphological constraints reach a maximum at mid-development (the "phylotypic" stage), genomic constraints appear to decrease in a monotonous manner over developmental time.

View Article: PubMed Central - PubMed

Affiliation: Université de Lausanne, Département d'Ecologie et d'Evolution, Quartier Sorge, Lausanne, Switzerland.

ABSTRACT
Constraints in embryonic development are thought to bias the direction of evolution by making some changes less likely, and others more likely, depending on their consequences on ontogeny. Here, we characterize the constraints acting on genome evolution in vertebrates. We used gene expression data from two vertebrates: zebrafish, using a microarray experiment spanning 14 stages of development, and mouse, using EST counts for 26 stages of development. We show that, in both species, genes expressed early in development (1) have a more dramatic effect of knock-out or mutation and (2) are more likely to revert to single copy after whole genome duplication, relative to genes expressed late. This supports high constraints on early stages of vertebrate development, making them less open to innovations (gene gain or gene loss). Results are robust to different sources of data -- gene expression from microarrays, ESTs, or in situ hybridizations; and mutants from directed KO, transgenic insertions, point mutations, or morpholinos. We determine the pattern of these constraints, which differs from the model used to describe vertebrate morphological conservation ("hourglass" model). While morphological constraints reach a maximum at mid-development (the "phylotypic" stage), genomic constraints appear to decrease in a monotonous manner over developmental time.

Show MeSH