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Transcriptomic prediction of pig Leg1s functions in HepG2 cells

ABSTRACT: The newly identified liver-enriched gene 1 (Leg1) encodes a protein with characteristic Domain of Unknown Function 781 (DUF781/LEG1) domain constituting a protein family with only one member. Functional study in zebrafish suggested that Leg1 genes were involved in the liver development, while the platypus MLP homolog that was enriched in mammary gland and milk acts as an anti-bacterial substance. However, no functional study on eutherian Leg1s has been published at present. Thus, we first report here a functional prediction research in a cellular model. As previously reported, eutherian Leg1s could be classified into three paralogous groups. Pig has all three Leg1 genes, while human and mouse only have retained Leg1a. Hence, pig is an ideal model to study the gene function. RNA-seq was then performed by overexpression of pig Leg1s and platypus MLP in the HepG2 cells. Enrichment analysis showed that pLeg1a and pLeg1b might be of little function in the liver cell; however, pLeg1c was probably involved in the ER stress response and protein folding. Additionally, gene set enrichment analysis revealed that platypus MLP has anti-bacterial activity confirming the functional study in the platypus. Therefore, our study, from the transcriptomic perspective of view, concluded that the mammalian Leg1s have different functions in the liver cells due to subfunctionalization of the paralogous genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145329 | GEO | 2020/05/01

REPOSITORIES: GEO

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Evolutionary and Molecular Characterization of liver enriched gene 1

Project description:Liver enriched gene 1 (Leg1) is a newly identified gene with few functional information. To know the function of Leg1 in mammals, a phylogenetic study was first conducted and indicated that Leg1 is an ancient gene, existing from bacteria to mammals. Analysis of pig genome shows the presence of three copies of pig Leg1s (pLeg1), which could be grouped to Leg1a, Leg1b, and Leg1c clades, respectively. Purifying force acts upon the evolution of Leg1 genes, making them highly likely be functional constraint.Additionally, expression analysis of pLeg1 in combination with the available expression data of human and mouse Leg1s suggests that the eutherian Leg1s might preserve similar function in contrary to those of zebrafish and platypus. Therefore, pLeg1a might provide essential information regarding eutherian Leg1a. In our work, pLeg1a and its coding protein pLEG1a display high similarities to its human and mouse counterparts in terms of gene organization, expression pattern, glycosylation, structures. Moreover, preliminary functional study using RNA-seq suggested that pLeg1a involves in the lipid homeostasis. In conclusion, our study has provided some basic information regarding the evolution, and function of Leg1 genes, which could be applied to further validation of Leg1.

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