Origin and evolution of the metazoan non-coding regulatory genome: Insights from the sponge Amphimedon queenslandica

Gaiti, Federico (2017). Origin and evolution of the metazoan non-coding regulatory genome: Insights from the sponge Amphimedon queenslandica PhD Thesis, School of Biological Sciences, The University of Queensland. doi:10.14264/uql.2017.494

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Author Gaiti, Federico
Thesis Title Origin and evolution of the metazoan non-coding regulatory genome: Insights from the sponge Amphimedon queenslandica
Formatted title
Origin and evolution of the metazoan non-coding regulatory genome: Insights from the sponge Amphimedon queenslandica
School, Centre or Institute School of Biological Sciences
Institution The University of Queensland
DOI 10.14264/uql.2017.494
Publication date 2017-04-10
Thesis type PhD Thesis
Supervisor Bernard M. Degnan
Milos Tanurdzic
Selene L. Fernandez-Valverde
Total pages 165
Total colour pages 25
Total black and white pages 140
Language eng
Subjects 0601 Biochemistry and Cell Biology
0604 Genetics
0603 Evolutionary Biology
Formatted abstract
Although early-branching non-eumetazoan animals (poriferans and ctenophores) possess
a repertoire of transcription factors and other developmental genes similar to that of modern
eumetazoans (cnidarians, placozoans and bilaterians), the nature and complexity of their
regulatory capabilities still remain to be elucidated. It is, therefore, unclear if complex
regulatory landscapes, which appear to underlie eumetazoan complexity and diversity,
evolved earlier and were part of the genomic landscape of the very first crown animals. To
this end, I undertake a systematic investigation of long non-coding RNAs (lncRNAs) and
generate genome-wide maps of enhancer elements in the sponge Amphimedon
queenslandica
. As a sponge, Amphimedon has one of the least complex animal body plans
and is an extant representative of one of the oldest animal phyletic lineages. Despite its
morphological simplicity, I show that this sponge shares a conserved gene regulatory
landscape with more morphologically-complex eumetazoans.

Specifically, Amphimedon developmentally expresses an array of lncRNAs in similar
manner to their eumetazoan counterparts. RNA-seq and CEL-seq analyses reveal that
sponge lncRNA expression is restricted to specific developmental periods and correlates
well with major developmental milestones – typical hallmarks of regulatory molecules. In situ
hybridization analysis of a subset of Amphimedon lncRNAs reveals their expression is also
restricted to specific cell-types and localized to distinct cellular domains. Subsets of sponge
lncRNAs appear to constitute integral parts of evolutionarily conserved co-expression
modules, which contain known developmental regulatory genes (e.g., TGF-b). Sponge
intergenic lncRNAs can also be separated in two distinct populations of poly(A)+ transcripts
based on the chromatin status at their transcription start sites, resembling those found in
bilaterians. These results indicate that lncRNAs are an ancient feature of the metazoan
regulatory system, suggesting that the last common ancestor of animals had much more
complex non-coding RNA regulatory capacities than previously thought. These findings are
also consistent with lncRNAs being important developmental regulators that operate in
conserved developmental gene modules, despite their lack of apparent sequence
conservation.

In addition, I collect an extensive ChIP-seq compendium of histone post-translational
modifications (PTMs) in Amphimedon, and show that, despite its simple morphology, the
combinatorial patterns of histone PTMs that are central to gene regulation in
morphologically-complex bilaterians and cnidarians are present in this sponge. Based on
these histone PTMs patterns, I identify enhancer elements and other chromatin-related
regulatory features that can now be deemed to be unique to multicellular animals. Strikingly,
Amphimedon enhancers appear to be enriched in the vicinity of developmental genes and
in metazoan-specific microsyntenic units, suggesting that their genomic location is
extremely ancient and places constraints on the evolution of surrounding genes.

Collectively, this first in-depth analysis of gene regulation in a non-eumetazoan suggests
that a major shift in genome regulatory complexity occurred along the metazoan stem, in
concert with the evolution of the metazoan multicellular condition. These results are
therefore consistent with complex gene regulation originating at least 700 million years ago,
predating the last common ancestor of extant animals, and argue that quantitative rather
than qualitative differences in regulatory mechanisms likely underlie the morphological and
functional diversification of eumetazoans.
Keyword Long non-coding RNA
Evolution
Histones
Gene regulation
Complexity
Cis-regulation
Enhancers
Multicellularity
Sponge
Chromatin
Additional Notes This document begins with Roman numerals, but the PDF numbering begins from page 1. Using the PDF numbering, color pages are: 29, 33, 50, 53, 57, 59-60, 62, 70-72, 75, 78, 80-81, 88, 92, 95, 97, 99, 102, 105, 124, 126, 128.

Document type: Thesis
Collections: UQ Theses (RHD) - Official
UQ Theses (RHD) - Open Access
 
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Created: Mon, 27 Mar 2017, 23:48:09 EST by Federico Gaiti on behalf of Learning and Research Services (UQ Library)