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Gene coexpression networks reveal key drivers of phenotypic divergence in porcine muscle.

Zhao X, Liu ZY, Liu QX - BMC Genomics (2015)

Bottom Line: Our results showed the regulation of muscle development might be more complex than had been previously acknowledged, and is regulated by the coordinated action of muscle, nerve and immunity related genes.Muscle phenotype divergence was found to be regulated by the divergence of coexpression network modules under artificial selection, and not by changes in the coding sequence of genes.Our results present multiple lines of evidence suggesting links between modules and muscle phenotypes, and provide insights into the molecular bases of genome organization in muscle development and phenotype variation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Developmental Genetics, Shandong Agricultural University, Tai'an, Shandong, China. zhxicgz@gmail.com.

ABSTRACT

Background: Domestication of the wild pig has led to obese and lean phenotype breeds, and evolutionary genome research has sought to identify the regulatory mechanisms underlying this phenotypic diversity. However, revealing the molecular mechanisms underlying muscle phenotype variation based on differentially expressed genes has proved to be difficult. To characterize the mechanisms regulating muscle phenotype variation under artificial selection, we aimed to provide an integrated view of genome organization by weighted gene coexpression network analysis.

Results: Our analysis was based on 20 publicly available next-generation sequencing datasets of lean and obese pig muscle generated from 10 developmental stages. The evolution of the constructed coexpression modules was examined using the genome resequencing data of 37 domestic pigs and 11 wild boars. Our results showed the regulation of muscle development might be more complex than had been previously acknowledged, and is regulated by the coordinated action of muscle, nerve and immunity related genes. Breed-specific modules that regulated muscle phenotype divergence were identified, and hundreds of hub genes with major roles in muscle development were determined to be responsible for key functional distinctions between breeds. Our evolutionary analysis showed that the role of changes in the coding sequence under positive selection in muscle phenotype divergence was minor.

Conclusions: Muscle phenotype divergence was found to be regulated by the divergence of coexpression network modules under artificial selection, and not by changes in the coding sequence of genes. Our results present multiple lines of evidence suggesting links between modules and muscle phenotypes, and provide insights into the molecular bases of genome organization in muscle development and phenotype variation.

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Visualization of breed-specific gene coexpression networks in prenatal animals. (A) LT-yellow green (B) LT-purple (C) LT-blue (D) Lde-tan (E) LDE-red (F) Lde-pink (G) Lde-turquoise (H) Lde-midnight blue (I) Lde-blue. The top 300 connections are shown for each module. Dots correspond to genes and lines to connections; hubs genes have at least 15 connections. Where the gene symbols are unknown, gene IDs are shown.
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Fig3: Visualization of breed-specific gene coexpression networks in prenatal animals. (A) LT-yellow green (B) LT-purple (C) LT-blue (D) Lde-tan (E) LDE-red (F) Lde-pink (G) Lde-turquoise (H) Lde-midnight blue (I) Lde-blue. The top 300 connections are shown for each module. Dots correspond to genes and lines to connections; hubs genes have at least 15 connections. Where the gene symbols are unknown, gene IDs are shown.

Mentions: Differences in transcriptional levels are important for studying the evolutionary basis of phenotypic differences at the molecular level [18]. Differences in network modules could provide a basis for better understanding of the differences in muscle development between lean and obese pigs. In this study, we identified six highly lean-specific modules and five highly obese-specific modules in the prenatal animals (Additional file 1: Table S6 and Table S7). A GO analysis of these module genes revealed that nine of these modules were involved in muscle development, neuron development and cellular response (Additional file 1: Table S8 and Table S9). Hub genes involved in muscle development were enriched in six lean-specific modules (HSBP1 in Lde-blue; MYL1 and DLK1 in Lde-midnight blue; MAP4 and FERMT2 in Lde-only-turquoise; TPM2, TCEA3, ZFP36L1, DES, TNNT3, and ANK3 in Lde-pink; MAPK12, MYLPF, and MYH2 in Lde-red; and SIRT1, OSR2, and MEF2D in Lde-tan) and in three obese-specific modules (GNB2L1 in LT-blue; ACTN2, MYH7, MYOZ3, MALAT1, PTP4A3, and ENO3 in LT-purple, and TNNI2 and DAG1 in LT-yellow green) (FigureĀ 3). The hub genes in the LT-dark red module were significantly enriched for genes involved in cellular response (RRAGD, EPHX1, TPD52 and PSMA2). Overall, a greater number of muscle development-related modules that regulate fiber number and muscle fiber composition were identified in lean Lde animals than in obese LT animals.Figure 3


Gene coexpression networks reveal key drivers of phenotypic divergence in porcine muscle.

Zhao X, Liu ZY, Liu QX - BMC Genomics (2015)

Visualization of breed-specific gene coexpression networks in prenatal animals. (A) LT-yellow green (B) LT-purple (C) LT-blue (D) Lde-tan (E) LDE-red (F) Lde-pink (G) Lde-turquoise (H) Lde-midnight blue (I) Lde-blue. The top 300 connections are shown for each module. Dots correspond to genes and lines to connections; hubs genes have at least 15 connections. Where the gene symbols are unknown, gene IDs are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4328970&req=5

Fig3: Visualization of breed-specific gene coexpression networks in prenatal animals. (A) LT-yellow green (B) LT-purple (C) LT-blue (D) Lde-tan (E) LDE-red (F) Lde-pink (G) Lde-turquoise (H) Lde-midnight blue (I) Lde-blue. The top 300 connections are shown for each module. Dots correspond to genes and lines to connections; hubs genes have at least 15 connections. Where the gene symbols are unknown, gene IDs are shown.
Mentions: Differences in transcriptional levels are important for studying the evolutionary basis of phenotypic differences at the molecular level [18]. Differences in network modules could provide a basis for better understanding of the differences in muscle development between lean and obese pigs. In this study, we identified six highly lean-specific modules and five highly obese-specific modules in the prenatal animals (Additional file 1: Table S6 and Table S7). A GO analysis of these module genes revealed that nine of these modules were involved in muscle development, neuron development and cellular response (Additional file 1: Table S8 and Table S9). Hub genes involved in muscle development were enriched in six lean-specific modules (HSBP1 in Lde-blue; MYL1 and DLK1 in Lde-midnight blue; MAP4 and FERMT2 in Lde-only-turquoise; TPM2, TCEA3, ZFP36L1, DES, TNNT3, and ANK3 in Lde-pink; MAPK12, MYLPF, and MYH2 in Lde-red; and SIRT1, OSR2, and MEF2D in Lde-tan) and in three obese-specific modules (GNB2L1 in LT-blue; ACTN2, MYH7, MYOZ3, MALAT1, PTP4A3, and ENO3 in LT-purple, and TNNI2 and DAG1 in LT-yellow green) (FigureĀ 3). The hub genes in the LT-dark red module were significantly enriched for genes involved in cellular response (RRAGD, EPHX1, TPD52 and PSMA2). Overall, a greater number of muscle development-related modules that regulate fiber number and muscle fiber composition were identified in lean Lde animals than in obese LT animals.Figure 3

Bottom Line: Our results showed the regulation of muscle development might be more complex than had been previously acknowledged, and is regulated by the coordinated action of muscle, nerve and immunity related genes.Muscle phenotype divergence was found to be regulated by the divergence of coexpression network modules under artificial selection, and not by changes in the coding sequence of genes.Our results present multiple lines of evidence suggesting links between modules and muscle phenotypes, and provide insights into the molecular bases of genome organization in muscle development and phenotype variation.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Developmental Genetics, Shandong Agricultural University, Tai'an, Shandong, China. zhxicgz@gmail.com.

ABSTRACT

Background: Domestication of the wild pig has led to obese and lean phenotype breeds, and evolutionary genome research has sought to identify the regulatory mechanisms underlying this phenotypic diversity. However, revealing the molecular mechanisms underlying muscle phenotype variation based on differentially expressed genes has proved to be difficult. To characterize the mechanisms regulating muscle phenotype variation under artificial selection, we aimed to provide an integrated view of genome organization by weighted gene coexpression network analysis.

Results: Our analysis was based on 20 publicly available next-generation sequencing datasets of lean and obese pig muscle generated from 10 developmental stages. The evolution of the constructed coexpression modules was examined using the genome resequencing data of 37 domestic pigs and 11 wild boars. Our results showed the regulation of muscle development might be more complex than had been previously acknowledged, and is regulated by the coordinated action of muscle, nerve and immunity related genes. Breed-specific modules that regulated muscle phenotype divergence were identified, and hundreds of hub genes with major roles in muscle development were determined to be responsible for key functional distinctions between breeds. Our evolutionary analysis showed that the role of changes in the coding sequence under positive selection in muscle phenotype divergence was minor.

Conclusions: Muscle phenotype divergence was found to be regulated by the divergence of coexpression network modules under artificial selection, and not by changes in the coding sequence of genes. Our results present multiple lines of evidence suggesting links between modules and muscle phenotypes, and provide insights into the molecular bases of genome organization in muscle development and phenotype variation.

Show MeSH
Related in: MedlinePlus