Limits...
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.

Show MeSH

Related in: MedlinePlus

Variation across mouse development of the ratio of genes with different Knock-Out phenotypes.(A) Ratio of expressed essential genes relative to “non essential” genes. At each time point, the ratio of the number of essential genes expressed on the number of “non essential” genes expressed is plotted. Detailed counts for each data point in Dataset S2. A weighted linear regression was fitted to the data and the regression line plotted. A Bonferroni multiple-testing correction was used to adjust the significance threshold (α = 0.05/6 = 0.0083). A gray box on the x-axis indicates the phylotypic period. (B) Ratio of expressed genes inducing abnormal phenotypes when non functional compared to non essential genes. The linear regression is not significant after multiple testing correction (r = −0.477; p = 0.014). (C) Ratio of expressed essential genes compared to genes inducing abnormal phenotypes when non functional. Legend as in Figure 4A.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2600815&req=5

pgen-1000311-g004: Variation across mouse development of the ratio of genes with different Knock-Out phenotypes.(A) Ratio of expressed essential genes relative to “non essential” genes. At each time point, the ratio of the number of essential genes expressed on the number of “non essential” genes expressed is plotted. Detailed counts for each data point in Dataset S2. A weighted linear regression was fitted to the data and the regression line plotted. A Bonferroni multiple-testing correction was used to adjust the significance threshold (α = 0.05/6 = 0.0083). A gray box on the x-axis indicates the phylotypic period. (B) Ratio of expressed genes inducing abnormal phenotypes when non functional compared to non essential genes. The linear regression is not significant after multiple testing correction (r = −0.477; p = 0.014). (C) Ratio of expressed essential genes compared to genes inducing abnormal phenotypes when non functional. Legend as in Figure 4A.

Mentions: We performed a similar analysis in mouse, with some differences of methodology due to the data available. For expression, we used of a large amount of EST (Expressed Sequence Tags) data from libraries spanning development, from which we deduced presence or absence of expression (see Methods). Only phenotypes obtained by the targeted knock-out technique were used. As knock-out experiments with no observable phenotype are reported in mouse, we can use these as a reference set, instead of non annotated genes as in zebrafish. The ratio of expressed essential genes to expressed reference genes is significantly negatively correlated with developmental time (Figure 4A), as in zebrafish (Figure 1).


Developmental constraints on vertebrate genome evolution.

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

Variation across mouse development of the ratio of genes with different Knock-Out phenotypes.(A) Ratio of expressed essential genes relative to “non essential” genes. At each time point, the ratio of the number of essential genes expressed on the number of “non essential” genes expressed is plotted. Detailed counts for each data point in Dataset S2. A weighted linear regression was fitted to the data and the regression line plotted. A Bonferroni multiple-testing correction was used to adjust the significance threshold (α = 0.05/6 = 0.0083). A gray box on the x-axis indicates the phylotypic period. (B) Ratio of expressed genes inducing abnormal phenotypes when non functional compared to non essential genes. The linear regression is not significant after multiple testing correction (r = −0.477; p = 0.014). (C) Ratio of expressed essential genes compared to genes inducing abnormal phenotypes when non functional. Legend as in Figure 4A.
© Copyright Policy
Related In: Results  -  Collection

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

pgen-1000311-g004: Variation across mouse development of the ratio of genes with different Knock-Out phenotypes.(A) Ratio of expressed essential genes relative to “non essential” genes. At each time point, the ratio of the number of essential genes expressed on the number of “non essential” genes expressed is plotted. Detailed counts for each data point in Dataset S2. A weighted linear regression was fitted to the data and the regression line plotted. A Bonferroni multiple-testing correction was used to adjust the significance threshold (α = 0.05/6 = 0.0083). A gray box on the x-axis indicates the phylotypic period. (B) Ratio of expressed genes inducing abnormal phenotypes when non functional compared to non essential genes. The linear regression is not significant after multiple testing correction (r = −0.477; p = 0.014). (C) Ratio of expressed essential genes compared to genes inducing abnormal phenotypes when non functional. Legend as in Figure 4A.
Mentions: We performed a similar analysis in mouse, with some differences of methodology due to the data available. For expression, we used of a large amount of EST (Expressed Sequence Tags) data from libraries spanning development, from which we deduced presence or absence of expression (see Methods). Only phenotypes obtained by the targeted knock-out technique were used. As knock-out experiments with no observable phenotype are reported in mouse, we can use these as a reference set, instead of non annotated genes as in zebrafish. The ratio of expressed essential genes to expressed reference genes is significantly negatively correlated with developmental time (Figure 4A), as in zebrafish (Figure 1).

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
Related in: MedlinePlus