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Human and chimpanzee gene expression differences replicated in mice fed different diets.

Somel M, Creely H, Franz H, Mueller U, Lachmann M, Khaitovich P, Pääbo S - PLoS ONE (2008)

Bottom Line: The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain.Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes.Our results suggest that the mouse can be used to study at least some aspects of human-specific traits.

View Article: PubMed Central - PubMed

Affiliation: Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. somel@eva.mpg.de

ABSTRACT
Although the human diet is markedly different from the diets of closely related primate species, the influence of diet on phenotypic and genetic differences between humans and other primates is unknown. In this study, we analyzed gene expression in laboratory mice fed diets typical of humans and of chimpanzees. The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain. Importantly, 10% of the genes that differ in their expression between humans and chimpanzee livers differed also between the livers of mice fed the human and chimpanzee diets. Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes. Our results suggest that the mouse can be used to study at least some aspects of human-specific traits.

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Sequence divergence of genes potentially involved in human-chimpanzee dietary differences.Median sequence divergence estimates between humans and chimpanzees is shown for promoter regions (left) and for amino acid sequences (Ka/Ki) (right). The error bars represent 95% bootstrap confidence intervals for the median, calculated by resampling from the divergence estimate distributions for each gene set 1,000 times. Diet diff.-Human genes with mouse orthologs showing diet-related human-chimpanzee expression differences in liver; All diff.-Human genes with mouse orthologs showing human-chimpanzee expression differences in liver; All exprs.-Human genes with mouse orthologs expressed in liver; All genes-All available human genes with mouse orthologs.
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pone-0001504-g003: Sequence divergence of genes potentially involved in human-chimpanzee dietary differences.Median sequence divergence estimates between humans and chimpanzees is shown for promoter regions (left) and for amino acid sequences (Ka/Ki) (right). The error bars represent 95% bootstrap confidence intervals for the median, calculated by resampling from the divergence estimate distributions for each gene set 1,000 times. Diet diff.-Human genes with mouse orthologs showing diet-related human-chimpanzee expression differences in liver; All diff.-Human genes with mouse orthologs showing human-chimpanzee expression differences in liver; All exprs.-Human genes with mouse orthologs expressed in liver; All genes-All available human genes with mouse orthologs.

Mentions: In order to gauge the rate of evolution of the 117 genes affected by diet, we compared the DNA sequence divergence in their promoter regions [13] between humans and chimpanzees and the inferred amino acid sequences of their encoded proteins [17] to (i) all orthologous human and mouse genes that differ in gene expression between human and chimpanzees in liver, (ii) all human-mouse orthologs expressed in human or chimpanzee livers, and (iii) all human-mouse orthologs irrespective of their expression in liver. We find that both the promoter sequences (one-sided permutation test p = 0.01, 0.06, 0.04, respectively) and the amino acid sequences (p = 0.002, <0.001, 0.043, respectively) evolve faster in the 117 genes than in the latter sets of genes (Figure 3; Table S8). We also tested whether there is any significant overlap between the 117 genes that are affected by diet and differ in expression between humans and chimpanzees and either genes positively selected in their promoters in the human and chimpanzee lineages recently published by Haygood et al. [18] or in their amino acid sequences recently published by Bakewell et al. [19]. We find no such significant overlaps. This may not be surprising given the presumably high false negative rate pertaining to the identification of relevant genes in our study as well as the other studies.


Human and chimpanzee gene expression differences replicated in mice fed different diets.

Somel M, Creely H, Franz H, Mueller U, Lachmann M, Khaitovich P, Pääbo S - PLoS ONE (2008)

Sequence divergence of genes potentially involved in human-chimpanzee dietary differences.Median sequence divergence estimates between humans and chimpanzees is shown for promoter regions (left) and for amino acid sequences (Ka/Ki) (right). The error bars represent 95% bootstrap confidence intervals for the median, calculated by resampling from the divergence estimate distributions for each gene set 1,000 times. Diet diff.-Human genes with mouse orthologs showing diet-related human-chimpanzee expression differences in liver; All diff.-Human genes with mouse orthologs showing human-chimpanzee expression differences in liver; All exprs.-Human genes with mouse orthologs expressed in liver; All genes-All available human genes with mouse orthologs.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2200793&req=5

pone-0001504-g003: Sequence divergence of genes potentially involved in human-chimpanzee dietary differences.Median sequence divergence estimates between humans and chimpanzees is shown for promoter regions (left) and for amino acid sequences (Ka/Ki) (right). The error bars represent 95% bootstrap confidence intervals for the median, calculated by resampling from the divergence estimate distributions for each gene set 1,000 times. Diet diff.-Human genes with mouse orthologs showing diet-related human-chimpanzee expression differences in liver; All diff.-Human genes with mouse orthologs showing human-chimpanzee expression differences in liver; All exprs.-Human genes with mouse orthologs expressed in liver; All genes-All available human genes with mouse orthologs.
Mentions: In order to gauge the rate of evolution of the 117 genes affected by diet, we compared the DNA sequence divergence in their promoter regions [13] between humans and chimpanzees and the inferred amino acid sequences of their encoded proteins [17] to (i) all orthologous human and mouse genes that differ in gene expression between human and chimpanzees in liver, (ii) all human-mouse orthologs expressed in human or chimpanzee livers, and (iii) all human-mouse orthologs irrespective of their expression in liver. We find that both the promoter sequences (one-sided permutation test p = 0.01, 0.06, 0.04, respectively) and the amino acid sequences (p = 0.002, <0.001, 0.043, respectively) evolve faster in the 117 genes than in the latter sets of genes (Figure 3; Table S8). We also tested whether there is any significant overlap between the 117 genes that are affected by diet and differ in expression between humans and chimpanzees and either genes positively selected in their promoters in the human and chimpanzee lineages recently published by Haygood et al. [18] or in their amino acid sequences recently published by Bakewell et al. [19]. We find no such significant overlaps. This may not be surprising given the presumably high false negative rate pertaining to the identification of relevant genes in our study as well as the other studies.

Bottom Line: The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain.Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes.Our results suggest that the mouse can be used to study at least some aspects of human-specific traits.

View Article: PubMed Central - PubMed

Affiliation: Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. somel@eva.mpg.de

ABSTRACT
Although the human diet is markedly different from the diets of closely related primate species, the influence of diet on phenotypic and genetic differences between humans and other primates is unknown. In this study, we analyzed gene expression in laboratory mice fed diets typical of humans and of chimpanzees. The effects of human diets were found to be significantly different from that of a chimpanzee diet in the mouse liver, but not in the brain. Importantly, 10% of the genes that differ in their expression between humans and chimpanzee livers differed also between the livers of mice fed the human and chimpanzee diets. Furthermore, both the promoter sequences and the amino acid sequences of these diet-related genes carry more differences between humans and chimpanzees than random genes. Our results suggest that the mouse can be used to study at least some aspects of human-specific traits.

Show MeSH