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Characterization and comparison of the tissue-related modules in human and mouse.

Yang R, Su B - PLoS ONE (2010)

Bottom Line: Modules, serving as the building blocks and operational units of biological systems, provide more information than individual genes.In addition, we defined a novel quantity, "total constraint intensity," a proxy of multiple constraints (of co-regulated genes and tissues where the co-regulation occurs) on the evolution of genes in module context.We demonstrate that the evolutionary rate of a gene is negatively correlated with its total constraint intensity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.

ABSTRACT

Background: Due to the advances of high throughput technology and data-collection approaches, we are now in an unprecedented position to understand the evolution of organisms. Great efforts have characterized many individual genes responsible for the interspecies divergence, yet little is known about the genome-wide divergence at a higher level. Modules, serving as the building blocks and operational units of biological systems, provide more information than individual genes. Hence, the comparative analysis between species at the module level would shed more light on the mechanisms underlying the evolution of organisms than the traditional comparative genomics approaches.

Results: We systematically identified the tissue-related modules using the iterative signature algorithm (ISA), and we detected 52 and 65 modules in the human and mouse genomes, respectively. The gene expression patterns indicate that all of these predicted modules have a high possibility of serving as real biological modules. In addition, we defined a novel quantity, "total constraint intensity," a proxy of multiple constraints (of co-regulated genes and tissues where the co-regulation occurs) on the evolution of genes in module context. We demonstrate that the evolutionary rate of a gene is negatively correlated with its total constraint intensity. Furthermore, there are modules coding the same essential biological processes, while their gene contents have diverged extensively between human and mouse.

Conclusions: Our results suggest that unlike the composition of module, which exhibits a great difference between human and mouse, the functional organization of the corresponding modules may evolve in a more conservative manner. Most importantly, our findings imply that similar biological processes can be carried out by different sets of genes from human and mouse, therefore, the functional data of individual genes from mouse may not apply to human in certain occasions.

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Histograph of the maximal similarity for the 65 mouse modules to all the human modules.The trend line is fitted by the lowess algorithm [54]. This plot displays a few pairs of human-mouse modules with relatively high similarity.
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pone-0011730-g005: Histograph of the maximal similarity for the 65 mouse modules to all the human modules.The trend line is fitted by the lowess algorithm [54]. This plot displays a few pairs of human-mouse modules with relatively high similarity.

Mentions: Considering that genes often “group” into gene sets and provide mutual functional backups resulting from genetic redundancy [23], [24], we further investigated the modified similarity for each pair of modules (one from human and the other from mouse) by taking into account the paralogs (see Figure 3). We observe that there is an increase for most of the original similarities, but the majority of the modified similarities are still less than 0.3 (see Figure 4). We then ask whether there are a few “conserved” modules among these modules. For each mouse module M, we define its counterpart which has the maximal similarity to M in human. As illustrated in Figure 5, the histograph of the maximal similarity showed that more than half of the pairs share less than 15% genes, and there are only four pairs of modules with relatively high between-species similarity. For instance, the first pair of modules, which are specifically expressed in the liver, have 45% similarity. The second pair showed ∼28% similarity, both of which are highly expressed in the lung, but highly suppressed in the CD4+ and CD8+ T cell lines. Interestingly, the remaining two pairs are composed of a human module associated with the amygdale, cerebellum and hypothalamus, and two mouse counterparts, which are either highly expressed in the amygdale, cerebellum, hypothalamus, dorsal root ganglion and olfactory bulb, or dominant in the dorsal root ganglion and trigeminal ganglion. It is possible that the two mouse counterparts may originate from one de facto module, which was artificially split into two in the subsequent module-merging process because the similarity between them is high(0.558).


Characterization and comparison of the tissue-related modules in human and mouse.

Yang R, Su B - PLoS ONE (2010)

Histograph of the maximal similarity for the 65 mouse modules to all the human modules.The trend line is fitted by the lowess algorithm [54]. This plot displays a few pairs of human-mouse modules with relatively high similarity.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908688&req=5

pone-0011730-g005: Histograph of the maximal similarity for the 65 mouse modules to all the human modules.The trend line is fitted by the lowess algorithm [54]. This plot displays a few pairs of human-mouse modules with relatively high similarity.
Mentions: Considering that genes often “group” into gene sets and provide mutual functional backups resulting from genetic redundancy [23], [24], we further investigated the modified similarity for each pair of modules (one from human and the other from mouse) by taking into account the paralogs (see Figure 3). We observe that there is an increase for most of the original similarities, but the majority of the modified similarities are still less than 0.3 (see Figure 4). We then ask whether there are a few “conserved” modules among these modules. For each mouse module M, we define its counterpart which has the maximal similarity to M in human. As illustrated in Figure 5, the histograph of the maximal similarity showed that more than half of the pairs share less than 15% genes, and there are only four pairs of modules with relatively high between-species similarity. For instance, the first pair of modules, which are specifically expressed in the liver, have 45% similarity. The second pair showed ∼28% similarity, both of which are highly expressed in the lung, but highly suppressed in the CD4+ and CD8+ T cell lines. Interestingly, the remaining two pairs are composed of a human module associated with the amygdale, cerebellum and hypothalamus, and two mouse counterparts, which are either highly expressed in the amygdale, cerebellum, hypothalamus, dorsal root ganglion and olfactory bulb, or dominant in the dorsal root ganglion and trigeminal ganglion. It is possible that the two mouse counterparts may originate from one de facto module, which was artificially split into two in the subsequent module-merging process because the similarity between them is high(0.558).

Bottom Line: Modules, serving as the building blocks and operational units of biological systems, provide more information than individual genes.In addition, we defined a novel quantity, "total constraint intensity," a proxy of multiple constraints (of co-regulated genes and tissues where the co-regulation occurs) on the evolution of genes in module context.We demonstrate that the evolutionary rate of a gene is negatively correlated with its total constraint intensity.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.

ABSTRACT

Background: Due to the advances of high throughput technology and data-collection approaches, we are now in an unprecedented position to understand the evolution of organisms. Great efforts have characterized many individual genes responsible for the interspecies divergence, yet little is known about the genome-wide divergence at a higher level. Modules, serving as the building blocks and operational units of biological systems, provide more information than individual genes. Hence, the comparative analysis between species at the module level would shed more light on the mechanisms underlying the evolution of organisms than the traditional comparative genomics approaches.

Results: We systematically identified the tissue-related modules using the iterative signature algorithm (ISA), and we detected 52 and 65 modules in the human and mouse genomes, respectively. The gene expression patterns indicate that all of these predicted modules have a high possibility of serving as real biological modules. In addition, we defined a novel quantity, "total constraint intensity," a proxy of multiple constraints (of co-regulated genes and tissues where the co-regulation occurs) on the evolution of genes in module context. We demonstrate that the evolutionary rate of a gene is negatively correlated with its total constraint intensity. Furthermore, there are modules coding the same essential biological processes, while their gene contents have diverged extensively between human and mouse.

Conclusions: Our results suggest that unlike the composition of module, which exhibits a great difference between human and mouse, the functional organization of the corresponding modules may evolve in a more conservative manner. Most importantly, our findings imply that similar biological processes can be carried out by different sets of genes from human and mouse, therefore, the functional data of individual genes from mouse may not apply to human in certain occasions.

Show MeSH