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The 3D genome of the frog Xenopus laevis

Llorente-Armijo, Sara (2020) BINP52 20192
Degree Projects in Bioinformatics
Abstract
The organization of DNA inside the nucleus has a crucial role in the regulation of gene expression. Tight gene regulation is especially critical during embryonic development and cell fate commitment. Xenopus laevis is a long-standing model organism for studying embryo development and cell reprogramming. However, genomics studies have been challenging due to its allotetraploid condition. Here, we perform an analysis of the 3D genome in endoderm and ectoderm cells from X. laevis embryos. We generate Hi-C contact maps for these samples and observe features of the chromatin architecture similar to the ones already reported in other organisms. We also observe chromatin interactions between the homoeologous chromosomes - those chromosomes that... (More)
The organization of DNA inside the nucleus has a crucial role in the regulation of gene expression. Tight gene regulation is especially critical during embryonic development and cell fate commitment. Xenopus laevis is a long-standing model organism for studying embryo development and cell reprogramming. However, genomics studies have been challenging due to its allotetraploid condition. Here, we perform an analysis of the 3D genome in endoderm and ectoderm cells from X. laevis embryos. We generate Hi-C contact maps for these samples and observe features of the chromatin architecture similar to the ones already reported in other organisms. We also observe chromatin interactions between the homoeologous chromosomes - those chromosomes that diverged through speciation and converged by interspecific hybridization in the genome of the frog X. laevis. We show that the contacts between these homoeologous chromosomes are most likely an artefact caused by the high identity at the sequence level. This high sequence identity is also responsible of the higher number of multimapping reads in X. laevis compared to other model organism. These results pave the way to better understand the genome of X. laevis and study the role of the chromatin architecture during embryo development and evolution in this long-standing model organism. (Less)
Popular Abstract
It is crucial that our cells express the right set of genes at the right time, for example, when we are fighting an infection or when our bodies are developing. Our genes are part of the 2 meters long molecule of DNA, which is in almost every single one of our cells. This DNA is stored in a cell nucleus that is only a few microns in diameter. You can already see the great challenge that our cells face, because they need to compact the genome into a very small space while still making sure that the genes are properly expressed. So just so you can get an idea of the tremendous level of compaction, this would be equivalent to fit The Great Wall of China inside an Olympic swimming pool.

The early development of an embryo is a vital moment.... (More)
It is crucial that our cells express the right set of genes at the right time, for example, when we are fighting an infection or when our bodies are developing. Our genes are part of the 2 meters long molecule of DNA, which is in almost every single one of our cells. This DNA is stored in a cell nucleus that is only a few microns in diameter. You can already see the great challenge that our cells face, because they need to compact the genome into a very small space while still making sure that the genes are properly expressed. So just so you can get an idea of the tremendous level of compaction, this would be equivalent to fit The Great Wall of China inside an Olympic swimming pool.

The early development of an embryo is a vital moment. According to Lewis Wolpert: “It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life” (Lewis Wolpert, 1986). Gastrulation is the moment when the fate of the cells of the embryo starts to be defined. Some cells will form the skin, others will be part of the brain or the heart. All these cells are different in shape and function, even though they all have the same genome. Work characterizing how cells defined their identity in the frog Xenopus laevis resulted in the Nobel Prize to John Gurdon in 2012. This frog is a long-standing model organism to study embryo development, but its special genome has hindered the genomic studies.

The genome of Xenopus laevis is like two genomes in one, since it comes from the fusion of the genomes of two ancestral species of frog. Therefore, the sequences between some chromosomes are very similar. In order to study how the genome of Xenopus laevis is packed in the cell nucleus, we first need to ensure that we are able to generate reliable and good-quality data from the genome of this special frog. This study addresses the challenges that rise in the frog Xenopus laevis when studying how its complex genome is compacted.

To understand how the genome is packed inside the nucleus, we study which regions of the genome are interacting. We use a sequencing technique that allows us to study the interactions along the whole genome, which is called Hi-C. From this technique, we obtain many pairs of sequences that are interacting. We then need to find where these sequences belong within the genome. Here, the challenges of the complex genome of Xenopus laevis appear.

A higher number of sequences compared to other organisms are reported to be found in more than one location along the genome of Xenopus laevis. These ambiguous sequences need to be filtered out, which make us lose the information of some interactions. On the other hand, we found interactions between the chromosomes that are very similar at the sequence level. We have shown that these interactions are not real but they are generated during the processing of the data. Both of these problems are caused by the high similarity between the two-genomes-in-one that make up the complex genome of Xenopus laevis. In conclusion, this study paves the way to better understand the genome of Xenopus laevis and unravel the role of DNA organization during the early embryonic development in this model organism.


Master’s Degree Project in Bioinformatics 60 credits 2020
Department of Biology, Lund University

Advisor: Juan M. Vaquerizas
Unit/Department: Regulatory Genomics, Max Planck Institute for Molecular Biomedicine, Muenster (Less)
Please use this url to cite or link to this publication:
author
Llorente-Armijo, Sara
supervisor
organization
course
BINP52 20192
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9014792
date added to LUP
2020-06-09 09:45:39
date last changed
2020-06-09 09:45:39
@misc{9014792,
  abstract     = {{The organization of DNA inside the nucleus has a crucial role in the regulation of gene expression. Tight gene regulation is especially critical during embryonic development and cell fate commitment. Xenopus laevis is a long-standing model organism for studying embryo development and cell reprogramming. However, genomics studies have been challenging due to its allotetraploid condition. Here, we perform an analysis of the 3D genome in endoderm and ectoderm cells from X. laevis embryos. We generate Hi-C contact maps for these samples and observe features of the chromatin architecture similar to the ones already reported in other organisms. We also observe chromatin interactions between the homoeologous chromosomes - those chromosomes that diverged through speciation and converged by interspecific hybridization in the genome of the frog X. laevis. We show that the contacts between these homoeologous chromosomes are most likely an artefact caused by the high identity at the sequence level. This high sequence identity is also responsible of the higher number of multimapping reads in X. laevis compared to other model organism. These results pave the way to better understand the genome of X. laevis and study the role of the chromatin architecture during embryo development and evolution in this long-standing model organism.}},
  author       = {{Llorente-Armijo, Sara}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{The 3D genome of the frog Xenopus laevis}},
  year         = {{2020}},
}