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Title :¡¡Consequence of genome duplication in Xenopus laevis: a new model to study aneuploidy in human diseases

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Abstract

Gene dosage imbalance by chromosomal duplication causes many human diseases, including Down syndrome and various types of cancers. Although we have learned about the molecular features of duplicated genes in yeast and plants, their roles in vertebrate development and cell homeostasis are heavily understudied, mainly because of a lack of proper model organisms. Here we present the allotetraploid genome of the African clawed frog Xenopus laevis that has maintained two copies of 9 homologous chromosomes (2N=18) for over 20 million years. Through collaborative efforts by the members of the international consortium, we have constructed 2.7 billion bases of scaffolds (JGI 7.1 version; N50 is 3.6 M bp), and validated the majority of their chromosomal locations with a large-scale BAC-FISH experiment. Surprisingly, we could also segregate the scaffolds to their diploid ancestors before allotetraploidization occurred (designated as L and S chromosomes, respectively, according to their size differences), using unique tandem repeat signatures.

To investigate functional consequences of duplicated genes, we performed large-scale transcriptome (RNA-seq) experiments across 11 different developmental stages and 14 adult tissues. Using over 25 million de novo assembled transcripts and other evidence, we annotated about 40,000 genes orthologous to more than 14,000 human genes. By comparing their expression patterns to its sister species Xenopus (Silurana) tropicalis, which has a diploid genome, we first confirmed that orthologous genes between these two species showed highly similar expression patterns. By analyzing the expression of two copies of duplicated genes (homoeologs), we found that they are more likely to contribute equally in early development, but one copy of them (mostly from L chromosomes) is more preferentially used in later developmental stages and adult tissues. These results provide comprehensive resources to make Xenopus an attractive model organism, not only in cell and developmental biology but also in systems biology and many other areas in biomedical research.

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Publications (*indicates shared first authorship)

1. Kwon T*, Chung M-I*, Gupta R, Baker JC, Marcotte EM, Wallingford JB (2014) Identifying direct target of transcription factor Rfx2 that coordinate ciliogenesis and cell movement Genomics Data,2:192-194

2. Kwon T, Huse HK, Vogel C, Whiteley M, Marcotte EM (2014) Protein-to-mRNA ratios are conserved between Pseudomonas strains. J. Proteome Res.,13(5):2370-2380 PMID:24742327¡¡