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\title{\bf Transcription-dependent DNA supercoils determine the 3D organization of dinoflagellate genomes}
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\author[1,,*,$\#$]{Georgi K. Marinov}
\author[3,7,*]{Alexandro E. Trevino}
\author[2,8,*]{Tingting Xiang}
\author[1]{John R. Pringle}
\author[1,6]{Anshul Kundaje}
\author[2]{Arthur R. Grossman}
\author[1,3,4,5,$\#$]{William J. Greenleaf}
\renewcommand\Affilfont{\itshape\small}
\affil[1]{Department of Genetics, Stanford University, Stanford, California 94305, USA}
\affil[2]{Carnegie Institution for Science, Department of Plant Biology, Stanford, California 94305, USA}
\affil[3]{Center for Personal Dynamic Regulomes, Stanford University, Stanford, California 94305, USA}
\affil[4]{Department of Applied Physics, Stanford University, Stanford, California 94305, USA}
\affil[5]{Chan Zuckerberg Biohub, San Francisco, California, USA}
\affil[6]{Department of Computer Science, Stanford University, Stanford, California 94305, USA}
\affil[7]{Department of Bioengineering, Stanford University, Stanford, California 94305, USA}
\affil[8]{Department of  Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC 28223, USA}
\affil[*]{These authors contributed equally to this work}
\affil[$\#$]{Corresponding author}
\date{}

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\begin{abstract}

\noindent {\normalsize \textbf{Unlike most eukaryotes, dinoflagellate chromosomes exist in a permanently condensed, liquid crystalline state and are primarily packaged by proteins of viral and bacterial origin, rather than by nucleosomal histones. Genes are organized into polycistronic arrays, and gene regulation is thought to be largely post-transcriptional. How dinoflagellate chromosomes are physically organized has long remained a mystery. Here, we analyze the 3D genome structure of \textit{Breviolum minutum}, a coral symbiont dinoflagellate. We find that the genome partitions into topologically associating domains of 100-2000 kilobases, not associated with chromatin loops. Domain boundaries instead correspond to transitions between convergent gene arrays. Importantly, transcriptional inhibition degrades these domains. This study points to transcription-induced supercoiling as a fundamental force shaping the physical genome. }
}
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\begin{figure*}[!ht]
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\includegraphics[width=18.5cm]{Fig1-V6.png}
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\caption{
{\bf \textit{B. minutum} genome is physically partitioned into topological domains defined by polycistronic gene arrays}. 
(A-C) Organization of dinoflagellate chromosomes. (A) Hi-C scaffolding of the \textit{B. minutum} draft genome assembly identifies 91 major pseudochromosomes $\geq$500kb in size. 
% (B) Hi-C scaffolding efficiency (black) relative to the previous assembly (grey) and a recent Hi-C assembly in donkey (color). Confident scaffolds are larger and make up a high percentage of the assembly size, while small scaffolds comprising collapsed repeats and other artifacts are typical. 
(B) Inset from (A). KR-normalized \cite{KR} 5-kb resolution Hi-C map for pseudochromosome 10. Pseudochromosomes are physically partitioned into strong topological domains (``dinoTADs''). 
(C) Focus on a single topological domain, inset from (D). The usual signs of loop extrusion domains (presence of loops and stripes in Hi-C maps) are not observed in dinoTADs. 
(D) The number of dinoTADs per chromosome scales with chromosome size.
(E) Comparison of \textit{H. sapiens} (grey) and \textit{B. minutum} (yellow) topological domain sizes.
(F-H) Boundaries of dinoTADs are primarily associated with transitions between convergent polycistronic gene arrays. 
(F) Shown is the Hi-C map for pseudochromosome 10 together with transcript levels on the forward and the reverse strands. 
(G) Average Hi-C contacts across dinoTAD boundaries.
(H) Average forward- and reverse-strand RNA-seq contacts across dinoTAD boundaries.
}
\label{Fig1}
\end{figure*}

The three dimensional organization of genomes and its functional consequences have attracted much attention in recent years, especially in mammalian systems. These studies have by now identified multiple physical mechanisms underlying genome folding \cite{Szabo2019}. Two main topological forces are currently thought to drive 3D organization. Associations between similar chromatin states drive the formation of compartments, and this mechanism is probably present in most eukaryotes \cite{Szabo2019}. Better known (and more prominent in mammalian genomes) are the constraints on cohesin-mediated loop extrusion \cite{Rao2014}, imposed by pairs of boundary elements specified by occupancy sites of the CTCF insulation factor. They drive the formation of topologically associating loop extrusion domains (TADs), approximately 100-1000 kbp in size \cite{Rao2014}. 

Three-dimensional genome architecture has been proposed to have multiple important functional consequences for gene regulation \cite{Narendra2015,Vian2018}, organismal development \cite{Lupianez2015}, replication \cite{Pope2014}, mutational processes \cite{Canela2017}, and others. However, how functional activity in turn impacts genome organization is still poorly understood, and little is known how these biophysical properties vary across eukaryotes. 

Dinoflagellates are a diverse, widespread lineage of eukaryotes that play major roles in aquatic ecosystems. As an example, the association of dinoflagellates in the Symbiodiniaceae clade \cite{LaJeunesse2018} with reef-building coral species provides the metabolic basis for vital and highly biologically diverse reef ecosystems. 

Dinoflagellates are also a unique lineage possessing numerous highly divergent molecular features relative to other eukaryotic organisms \cite{Hackett2004}. Nucleosomal packaging of chromatin evolved in archaea and developed into its present form, shared across all eukaryotes, prior to the time of the Last Eukaryotic Common Ancestor (LECA) \cite{Talbert2019}. All living eukaryotes ancestrally possess four core nucleosomal histones (H2A, H2B, H3 and H4), each featuring long unstructured N-terminal tails. These tails, as well as a few residues in the histone fold domain, are subject to extensive posttranslational modifications, serving as recruitment platforms for effector domain-containing proteins thus forming the basis of the so called ``histone code''\cite{Jenuwein2001} and playing important roles in essentially all biochemical processes involving chromatin. The code's fundamental importance is strongly underscored by the fact that key histone code residues are almost invariant across eukaryotes \cite{Postberg2010}. 

Dinoflagellates are a striking exception. Their chromosomes exist in a liquid crystalline state, are permanently condensed throughout the cell cycle, and are characterized by a very low DNA to protein ratio of 1:10 (compared to the usual 1:1 \cite{Herzog1981}). This is because, even though histone genes (although highly divergent) are retained in dinoflagellate genomes  \cite{Marinov2015}, a combination of virus-derived dinoflagellate-specific nucleoproteins (DVNPs) and bacterial-derived histone-like proteins (HLPs) have taken over as the main DNA packaging components \cite{Gornik2012,Jano2017}.

The functional organization of dinoflagellate genomes is also unusual, though not without some parallels \cite{Lukes2009}, as genes are organized into polycistronic gene arrays transcribed as a single unit, with individual mRNAs generated through \textit{trans}-splicing; it is generally thought that transcriptional regulation is largely absent. In addition, despite being relatively small unicellular organisms, their genomes are often very large in size (up to two orders of magnitude larger than mammalian genomes). 

These fascinating features of dinoflagellate nuclei simultaneously present numerous intriguing questions regarding the adaptation of the conventional eukaryotic gene regulation mechanisms to the general absence of nucleosomal chromatin, and also provide an opportunity to explore the biophysical forces underlying genomic organization in the context of such an exceptional natural experiment. 

Here, we chart the 3D genome organization of the coral symbiont \textit{Breviolum minutum} (previously \textit{Symbiodinium minutum}), and uncover a novel mechanism for its formation. 

We first generated three genome-wide chromosome conformation capture (Hi-C) libraries for the \textit{B. minutum} SSB01 strain using a slight modification of the standard \textit{in situ} Hi-C protocol \cite{Rao2014}, including one under elevated temperature conditions. We obtained between $\sim$150 and 220 million distinct Hi-C contacts from each library (Supplementary Table \ref{TableS1}). We pooled reads from all samples and processed them against the existing, highly fragmented \textit{B. minutum} assembly \cite{Shoguchi2013}, then used the resulting Hi-C maps to generate a chromosome-level assembly scaffolding using established methods \cite{Dudchenko2017} (see Supplementary Methods for details). The resulting assembly consists of 91 major pseudochromosomes $\geq$ 500 kbp in size, encompassing $\sim$94\% of the total sequence, with 85 of them $\geq$1 Mbp (Figure \ref{Fig1}A, B and Supplementary Figure \ref{FigS1} A). The longest major pseudochromosomes are $\sim$11 Mbp in size, with a median length of 6.7 Mbp (Supplementary Figure \ref{FigS1}A). At 1-Mbp resolution, they exhibit a bipartite (on a few occasions tripartite) structure, with two major interacting domains (Supplementary Figure \ref{FigS2}). 

This assembly likely underestimates the total genome size, as the original set of contigs clearly contains a number of collapsed repeats, a common feature of Hi-C-based genome assemblies (Figure \ref{Fig1}A, lower right). We note that our assembly disagrees with published reports, which suggest $\sim$20 chromosomes based on microscopy images \cite{Shoguchi2013}. Nonetheless, Hi-C analysis strongly suggests the physical separation of a larger number of pseudochromosomes in the nucleus, as does the recent chromosome-level assembly of \textit{F. kawagutii} (another Symbiodiniaceae species) \cite{Li2020}. We expect truly complete assemblies that leverage a combination of long-read and Hi-C sequencing methods to become available in the near future. 

High-resolution (5 kbp) maps revealed the existence of strong topological domains ranging in length from $\leq$ 200 kbp to $\geq$2 Mbp (Figure \ref{Fig1}B-E, Supplementary Figures \ref{FigS3}--\ref{FigS13}). In mammals, where TADs are best documented \cite{Rao2014}, TAD boundaries are demarcated by opposite-orientation pairs of CTCF sites blocking the process of loop extrusion by cohesin rings \cite{Szabo2019}. Constraints on loop extrusion are reflected in high-resolution Hi-C maps by the presence of loops at TAD boundaries and ``stripes'' on the edges of TAD blocks \cite{Vian2018}. However, we observed no loop or stripe features in \textit{B. minutum} (Figure \ref{Fig1}C), suggesting that dinoflagellate TADs are formed by a different mechanism. We term these domains ``dinoTADs'' to distinguish them from the loop extrusion-related domains in vertebrates. The number of dinoTADs appears to be a function of the chromosome size (Figure \ref{Fig1}D), while comparison with mammalian TADs reveals dinoTADs to be considerably larger  (Figure \ref{Fig1}E).

In order to understand the formation of dinoTADs, we compared Hi-C maps to available annotation features for \textit{B. minutum}, in particular transcriptomic data (Supplementary Methods). Remarkably, we found that each dinoTAD corresponds to a pair of divergent gene arrays (Figure \ref{Fig1}F), while boundaries between dinoTADs coincide with regions of convergence between gene arrays (Figure \ref{Fig1}G-H). 

\begin{figure*}
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\caption{
{\bf Decompaction of dinoTADs upon transcriptional inhibition supports the transcription-induced supercoiling model for their formation}. Shown is pseudochromosome 10 as in Figure \ref{Fig1}. 
(A) Outline of transcription inhibition experiments carried out using $\alpha$-amanitin (orange) and triptolide (purple).
(B) Time course and dosages of transcriptional inhibition.
(C) Comparison of cell function, measured by PSII photosythetic efficiency test (left), and cell viability, measured by a colony counting assay (right), between $\alpha$-amanitin-treated and untreated samples over time. 
(D) KR-normalized Hi-C maps (50-kb resolution) at 0 hours, 24 hours and 48 hours (high dose) after $\alpha$-amanitin treatment show marked loss of dinoTADs.
(E) KR-normalized Hi-C maps (50-kb resolution) at 8 hours, 24 hours and 48 hours (high dose) after triptolide treatment show reduction of insulation at dinoTAD boundaries.
(F) Metaplots of Hi-C signal around domain boundaries (50-kb resolution; see Supplementary Methods for details).
(G) Amplification of \textit{TOP2} and \textit{TOP3} topoisomerase homolog genes in dinoflagellates compated to other unicellular eukaryotes. Transcriptome assemblies from the MMETSP \cite{MMETSP} were used (See Supplementary Methods for details). 
(H) Transcription-induced supercoiling as the main topological force driving the physical organization of dinoflagellate chromosomes. Transcribing RNA Polymerase molecules introduce negative and positive DNA supercoling behind and ahead of the transcription machinery, respectively, and the interactions of negatively supercoiled domains could explain the physical association of divergently-oriented gene arrays. Topological insulation could be driven by supercoiling-related effects, or by unknown boundary elements. Also unknown at present is the role of the expanded repertoire of topoisomerases. 
\label{Fig2}}
\end{center}
\end{figure*}

Numerous models for dinoflagellate chromosome organization have been suggested since the 1960s, primarily based on electron microscopy. These include proposals that chromosomes are organized as ``toroidal chromonemas'' \cite{Oakley1979}, ``stacks of discs'' \cite{Livolant1978}, ``cored pineapples'' \cite{Levi2008}, or around ``central core fibers'' \cite{Spector1981}. Most of these models imply specific topological constraints maintaining the proposed shapes. 

The Hi-C patterns we observe instead strongly suggest a role for dynamic transcription-dependent DNA supercoiling in dinoTAD formation. Studies of 3D genome organization in bacteria have suggested that transcription can cause the formation of self-interacting domains \cite{Le2013}, and similar mechanisms have been proposed as an explanation for topological features observed in the yeast \textit{Schizosaccharomyces pombe} \cite{Benedetti2017}. Transcription can affect topological features due to its effects on DNA supercoiling \cite{Wu1988} -- the torque generated by RNA polymerase causes positive supercoiling in front of the transcription bubble and negative supercoiling behind it. Formation of plectonemes, nucleosome remodeling, or alteration in DNA structure are among the possible consequences \cite{Teves2014}. Transcription-driven plectoneme formation coinciding with long dinoflagellate gene arrays is an intuitive explanation for the compact dinoTADs we observe, although it is also possible that other topological constraints are responsible. 

The transcription-induced supercoiling model makes a clear prediction that can distinguish these possibilities -- inhibition of transcription should lead to the decompaction of dinoTADs. 

We first compared Hi-C maps for \textit{B. minutum} cells grown at 27$\,^{\circ}\mathrm{C}$ and at 34$\,^{\circ}\mathrm{C}$, as exposure to heat stress could result in general reduction in transcription activity \cite{Levin2016}. Indeed, while we do not observe disappearance of dinoTADs in the 34$\,^{\circ}\mathrm{C}$ sample, we do observe mild dinoTAD decompaction and an increase in interactions across dinoTAD boundaries (Supplementary Figures \ref{FigS16}--\ref{FigS18}). 

To directly test the transcription-induced supercoiling model, we carried out transcription inhibition experiments using $\alpha$-amanitin and triptolide (Figure \ref{Fig2}A-B). Triptolide prevents transcription initiation by targeting the XPB subunit of the TFIIH complex, and is fast acting (within hours). In contract, $\alpha$-amanitin directly inhibits RNA Polymerase II, and usually takes $\geq$12 hours to act due to its slow uptake by cells \cite{Bensaude2011}. We note that well-established transcription inhibition conditions for \textit{B. minutum} are lacking, and it is quite possible that inhibitor uptake is more difficult than in mammalian cells. It is also possible that triptolide does not strongly inhibit transcription due to the divergence of dinoflagellate transcription machinery components. We therefore carried out two sets of experiments, one using a ``normal'' dose for each inhibitor (the one usually used for mammalian cells) and a ``high'' dose (4$\times$ higher), harvesting cells at 0, 8, 24 and 48 hours for triptolide and at 0, 16, 24 and 48 hours for $\alpha$-amanitin. 

Of note, we found that even a high concentration of 4 $\mu$g/mL $\alpha$-amanitin did not cause detectable decreases in photosynthetic efficiency or cell viability relative to untreated controls (Figure \ref{Fig2}C), thus excluding increased cell death as a confounding factor in our analysis.

Strikingly, treatment with $\alpha$-amanitin resulted in a progressive, near-complete disappearance of dinoTADs over 48 hours (Figure \ref{Fig2}D and F; Supplementary Figures \ref{FigS33}--\ref{FigS40}); the effects of a lower-dose treatment were more modest. Triptolide treatment did not trigger a disappearance of all topological structures, but nevertheless induced ``blurring'' of boundaries between dinoTADs (Figure \ref{Fig2}E-F; Supplementary Figures \ref{FigS36}--\ref{FigS39}); this milder effect, as mentioned above, is possibly the result of XPB protein divergence \cite{Shoguchi2013}. The effects of transcriptional inhibition were observed in both technical and biological replicates (Supplementary Figures \ref{FigS33}--\ref{FigS40}), and on aggregate across all dinoTADs (Figure \ref{Fig2}F). 

% \hl{Placeholder for potential EM data this week?}

Taken together, these observations support transcription-driven supercoiling as the primary mechanism being the formation of dinoTADs. Examination of dinoflagellate gene repertoires corroborates the hypothesis that their genomes contend with elevated torsional stress. We surveyed available transcriptome assemblies for dinoflagellates and a wide sampling of other unicellular eukaryotes \cite{MMETSP} and uncovered a striking expansion of topoisomerase II- and topoisomerase III-like genes (but not topoisomerase I-like genes) within dinoflagellates (Figure \ref{Fig1}D; Supplementary Figure \ref{FigS15}; Supplementary Table \ref{TableS2}); topoisomerases are necessary for relieving transcription-induced torsional stress \cite{Pommier2016}. 

We also note that topological insulation within dinoTADs is much stronger than self-interacting domains observed in bacteria or \textit{S. pombe} (Supplementary Figures \ref{FigS31}) and \ref{FigS32})), and that no such domains are observed in Hi-C datasets for kinetoplastids, the other well-known lineage of eukaryotes with highly prominent unidirectional polycistronic gene arrays and loss of transcription-level gene regulation (Supplementary Figures \ref{FigS30}).  

These differences are readily explained as the result of the unusual properties of dinoflagellates and underscore their importance as a unique natural experiment for understanding fundamental topological forces driving genome folding. 

Neither bacteria nor \textit{S. pombe} possess unidirectional gene arrays of length comparable to that of dinoflagellates; accordingly, the amount of torsional stress that can accumulate along their genomes is reduced. In addition, transcription activity in those lineages is strongly non-uniform along the length of the genome, unlike the situation in dinoflagellates.

The general absence of nucleosomes is the second, and perhaps more important key variable. In mammals, where genes as long as dinoTADs are quite common (due to the presence of extremely long introns), transcription-dependent DNA supercoiling is nevertheless not directly apparent as a topological force in Hi-C maps, nor is it seen in kinetoplastids, which lack transcriptional regulation and have long gene arrays, but have otherwise mostly conventional nucleosomal chromatin. However, as discussed above, the main topological force in most eukaryotes appears to be the interactions between similar chromatin states, while in metazoans loop extrusion domains are also observed \cite{Szabo2019}. But these interactions are not present in dinoflagellates as their genomes are not packaged by nucleosomes. The model emerging is therefore one in which transcription-induced plectonemes are free to form in dinoflagellate genomes but not in other eukaryotes, where nucleosomal chromatin prevents that, and they can also be quite large due to the long length of dinoflagellate gene arrays (Figure \ref{Fig2}H). 

In summary, we have presented the first map of the physical organization of a dinoflagellate genome using modern molecular tools and have found unexpected links to the functional organization of the genome. The folding of the dinoflagellate genome in 3D space appears to be primarily dependent on transcription, and more specifically, transcription-dependent DNA supercoiling. This model is supported by the co-association of topological domains with pairs of divergent unidirectional gene arrays, the large expansion of topoisomerase genes in dinoflagellate genomes, and, most importantly, the disappearance of dinoTADs upon general inhibition of transcription. As the only known eukaryotes that do not use histones to package DNA, dinoflagellates represent a unique evolutionary experiment that reveals aspects of genome biology that are otherwise masked by nucleosomal chromatin and insulation. This natural experiment also highlights the potential magnitude of transcription-induced supercoiling as a general organizing force for genomes given that transcription-induced torsional stress is present in all organisms.

Nevertheless, numerous unanswered questions remain. It is not known what roles histone genes play in dinoflagellate genome biology. Although clearly not extensively used, they are expressed by all known dinoflagellates \cite{Marinov2015}. ChIP-seq experiments using specifically raised antibodies against the divergent \textit{B. minutum} histones will be necessary to study their roles. It is also possible that as-yet unidentified boundary elements of markedly different chromatin state exist at the boundaries of gene arrays. The specific actions and genomic localization of topoisomerases, which are highly copy-number amplified in dinoflagellates, will also be critical for modeling and interpreting our results. Detailed mechanistic investigation of these and other topics in dinoflagellates will require the development of robust methods for their genetic manipulation, which remains a notoriously difficult problem.  On the other hand, the question of what exactly the interplay between nucleosomes, topoisomerases, torsional stress and genome folding in other eukaryotes is now emerges prominently. Since our Hi-C protocols report the population average across millions of cells, another open question is how local folding states are distributed at the single-cell level, or across the cell cycle, and how these states relate to transcription. Single-cell genomic and superresolution microscopy techniques are needed to resolve these questions. Finally, when exactly in evolution did this unique physical arrangement appear? As Hi-C is becoming a standard tool in the genome assembly toolkit, we expect its application to early branching dinoflagellate lineages and their nearest relatives (such as the perkinsids) to reveal the answers in the not too distant future.

\section*{Author contributions}

G.K.M. performed Hi-C experiments. G.K.M and A.E.T. analyzed the data. A.E.T. and T.X. carried out transcription inhibition experiments and cell viability experiments. T.X. carried out \textit{S. minutum} culture and heat stress treatment. W.J.G., A.R.G.. A.K. and J.R.P. supervised the study. G.K.M., A.E.T. and T.X. interpreted data and wrote manuscript with input from all authors. 

\section*{Acknowledgments}

\hl{This work was supported by NIH grants (P50HG007735, RO1 HG008140, U19AI057266 and UM1HG009442 to W.J.G., 1UM1HG009436 to W.J.G. and A.K., 1DP2OD022870-01 and 1U01HG009431 to A.K.), the Rita Allen Foundation (to W.J.G.), the Baxter Foundation Faculty Scholar Grant, and the Human Frontiers Science Program grant RGY006S (to W.J.G).} W.J.G is a Chan Zuckerberg Biohub investigator and acknowledges grants 2017-174468 and 2018-182817 from the Chan Zuckerberg Initiative. Fellowship support provided by the Stanford School of Medicine Dean's Fellowship (G.K.M.), the Siebel Scholars, the Enhancing Diversity in Graduate Education Program and the Weiland Family Fellowship (A.E.T.). This work is also supported by NSF-IOS EDGE Award 1645164 and Carnegie Venture grant 10907 (to T.X. and G.K.M.).

The authors would like to thank Zohar Shipony, \hl{Erez Lieberman Aiden}, Philip Cleves, and members of the Greenleaf, Kundaje, Pringle and Grossman labs for helpful discussion and suggestions regarding this work.

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\section*{Supplementary Methods}

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Except where otherwise stated, computational analyses were carried out using custom-written Python scripts.

\subsection*{\textit{B. minutum} cell culture}

The clonal axenic \textit{Symbiodinium}/\textit{Breviolum minutum} strain SSB01 was used in all experiments. Stock cultures were grown as previously described\cite{Xiang2013,Xiang2015} in Daigo's IMK medium for marine microalgae (Wako Pure Chemicals) supplemented with casein hydrolysate (IMK+Cas) at 27$\,^{\circ}\mathrm{C}$ at a light intensity of 10 $\mu$mol photons m$^{−2}$ s$^{−1}$ from Philips ALTO II 25-W bulbs on a 12-h-light:12-h-dark cycle. The medium was prepared in artificial seawater (ASW).

\subsection*{Transcription inhibition experiments}

For $\alpha$-amanitin treatment, \textit{Breviolum minutum} cells at a density of $\sim$1 $\times 10^6$ cells/mL were treated with $\alpha$-amanitin (Sigma-Aldrich, Cat \# A2263) at concentrations of 1 $\mu$g/mL (``normal'' dose) and 4 $\mu$g/mL (''high'') dose. 

Samples were harvested at 0, 24, and 48 hours after treatment.

For triptolide treatment, \textit{Breviolum minutum} cells at a density of $\sim$1 $\times 10^6$ cells/mL were treated with triptolide (Sigma-Aldrich, Cat \# T3652) at concentrations of 10 $\mu$M (``normal'' dose) and 40 $\mu$M (''high'') dose.

Samples were harvested fat 0, 8, 24 and 48 hours after treatment.

\subsection*{Cell viability measurements}

\subsubsection*{Photosynthetic activity}

Maximum quantum yields of photosystem II, $Fv/Fm = (Fm - F0)/Fm$ was used to indicate photosynthetic function. S. minutum cultures (approximately $10^6$ cells/mL) were collected and dark adapted for 5 min, and $Fv/Fm$ was determined using a Dual Pam-100 fluorometer (Heinz Walz).

\subsubsection*{Colony formation assay}

Fresh SSB01 cells were sampled at 0, 24 and 48 hours after the treatment of transcription inhibitor $\alpha$-amanitin. For each condition, cell suspensions were diluted 1:5 and 1:10 before plating 1 $\mu$L of each dilution on marine broth (BD) agar plates. Plates were incubated at 27$\,^{\circ}\mathrm{C}$ at a light intensity of 10 $\mu$mol photons m$^{−2}$ s$^{−1}$. Cell numbers on each plate were counted after three weeks.

\subsection*{Hi-C experiments}

The in situ Hi-C procedure used to map 3D genomic interactions in \textit{Symbiodinium} was adapted from previous studies\cite{Rao2014,Mumbach2016} as follows:

\textit{Symbiodinium minutum} SSBO1 cells were first crosslinked using 37\% formaldehyde (Sigma) at a final concentration of 1\% for 15 minutes at room temperature. Formaldehyde was then quenched using 2.5 M Glycine at a final concentration of 0.25 M. Cells were subsequently centrifuged at 2,000 $g$ for 5 minutes, washed once in 1$\times$ PBS, and stored at -80$\,^{\circ}\mathrm{C}$. 

Cell lysis was initiated by incubation with 250 $\mu$L of cold Hi-C Lysis Buffer (10 mM Tris-HCl pH 8.0, 10 mM NaCl, 0.2\% Igepal CA630) on ice for 15 minutes, followed by centrifugation at 2,500 $g$ for 5 minutes, a wash with 500 $\mu$L of cold Hi-C Lysis Buffer, and centrifugation at 2,500 $g$ for 5 minutes. The pellet was the resuspended in 50 $\mu$L of 0.5\% SDS and incubated at 62$\,^{\circ}\mathrm{C}$ for 10 minutes. SDS was quenched by adding 145 $\mu$L of H$_2$O and 25 $\mu$L of 10\% Triton X-100 and incubating at 37$\,^{\circ}\mathrm{C}$ for 15 minutes.

Restriction digestion was carried out by adding 25 $\mu$L of 10$\times$ NEBuffer 2 and 100 U of the MboI restriction enzyme (NEB, R0147) and incubating for $\geq$2 hours at 37$\,^{\circ}\mathrm{C}$ in a Thermomixer at 900 rpm. The reaction was then incubated at 62$\,^{\circ}\mathrm{C}$ for 20 minutes in order to inactivate the restriction enzyme. 

Fragment ends were filled in by adding 37.5 $\mu$L of 0.4 mM biotin-14-dATP (ThermoFisher Scientific, $\#$ 19524-016), 1.5 $\mu$L each of 10 mM dCTP, dGTP and dTTP, and 8 $\mu$L of 5U/$\mu$L DNA Polymerase I Large (Klenow) Fragment (NEB M0210). The reaction was the incubated at 37$\,^{\circ}\mathrm{C}$ in a Thermomixer at 900 rpm for 45 minutes.

Fragment end ligation was carried out by adding 663 $\mu$L H$_2$O, 120 $\mu$L 10$\times$ NEB T4 DNA ligase buffer (NEB B0202), 100 $\mu$L of 10\% Triton X-100, 12 $\mu$L of 10 mg/mL Bovine Serum Albumin (100$\times$ BSA, NEB), 5 $\mu$L of 400 U/$\mu$L T4 DNA Ligase (NEB M0202), and incubating at room temperature for $\geq$4 hours with rotation. 

Nuclei were then pelleted by centrifugation at 3,500 $g$ for 5 minutes; the pellet was resuspended in 200 $\mu$L ChIP Elution Buffer (1\% SDS, 0.1 M NaHCO$_3$), Proteinase K was added, and incubated at 65$\,^{\circ}\mathrm{C}$ overnight to reverse crosslinks. 

After addition of 600 $\mu$L 1$\times$TE buffer, DNA was sonicated using a Qsonica S-4000 with a 1/16'' tip for 3 minutes, with 10 second pulses at intensity 3.5, and 20 seconds rest between pulses. DNA was then purified using the MinElute PCR Purificaiton Kit (Qiagen $\#$28006), with elution in a total volume of 300 $\mu$L 1$\times$ EB buffer. 

For streptavidin pulldown of biotin-labeled DNA, 150 $\mu$L of 10 mg/mL Dynabeads MyOne Streptavidin T1 beads (Life Technologies, 65602) were separated on a magnetic stand, then washed with 400 $\mu$L of 1$\times$ TWB (Tween Washing Buffer; 5 mM Tris-HCl pH 7.5; 0.5 mM EDTA; 1 M NaCl; 0.05\% Tween 20). The beads were resuspended in 300 $\mu$L of 2$\times$ Binding Buffer (10 mM Tris-HCl pH 7.5, 1 mM EDTA; 2 M NaCl), the sonicated DNA was added, and the beads were incubated for $\geq$15 minutes at room temperature on a rotator. After separation on a magnetic stand, the beads were washed with 600 $\mu$L of 1$\times$ TWB, and heated at 55$\,^{\circ}\mathrm{C}$ in a Thermomixer with shaking for 2 minutes. After removal of the supernatant on a magnetic stand, the TWB wash and 55$\,^{\circ}\mathrm{C}$ incubation were repeated. 

Final libraries were prepared on beads using the NEBNext Ultra II DNA Library Prep Kit (NEB, $\#$E7645) as follows. End repair was carried out by resuspending beads in 50 $\mu$L 1$\times$ EB buffer, and adding 3 $\mu$L NEB Ultra End Repair Enzyme and 7 $\mu$L NEB Ultra End Repair Enzyme, followed by incubation at 20$\,^{\circ}\mathrm{C}$ for 30 minutes and then at 65$\,^{\circ}\mathrm{C}$ for 30 minutes. 

Adapters were ligated to DNA fragments by adding 30 $\mu$L Blunt Ligation mix, 1 $\mu$L Ligation Enhancer and 2.5 $\mu$L NEB Adapter, incubating at 20$\,^{\circ}\mathrm{C}$ for 20 minutes, adding 3 $\mu$L USER enzyme, and incubating at 37$\,^{\circ}\mathrm{C}$ for 15 minutes. 

Beads were then separated on a magnetic stand, and washed with 600 $\mu$L TWB for 2 minutes at 55$\,^{\circ}\mathrm{C}$, 1000 rpm in a Thermomixer. After separation on a magnetic stand, beads were washed in 100 $\mu$L 0.1 $\times$ TE buffer, then resuspended in 16 $\mu$L 0.1 $\times$ TE buffer, and heated at 98$\,^{\circ}\mathrm{C}$ for 10 minutes. 

For PCR, 5 $\mu$L of each of the i5 and i7 NEB Next sequencing adapters were added together with 25 $\mu$L 2$\times$ NEB Ultra PCR Mater Mix. PCR was carried out with a 98$\,^{\circ}\mathrm{C}$ incubation for 30 seconds and 12 cycles of 98$\,^{\circ}\mathrm{C}$ for 10 seconds, 65$\,^{\circ}\mathrm{C}$ for 30 seconds, and 72$\,^{\circ}\mathrm{C}$ for 1 minute, followed by incubation at 72$\,^{\circ}\mathrm{C}$ for 5 minutes. 

Beads were separated on a magnetic stand, and the supernatant was cleaned up using 1$\times$ AMPure XP beads. 

Libraries were sequenced in a paired-end format on a Illumina NextSeq instrument using NextSeq 500/550 high output kits (either 2$\times$75 or 2$\times$36 cycles). 

\subsection*{Hi-C data processing and assembly scaffolding}

% Sequencing reads were trimmed down to 36mers and aligned as using Bowtie\cite{Langmead2009} (version 1.0.1) with the following settings: \verb|-v 2| \verb|--k 2| \verb|-m 1| \verb|-t |--best| \verb|--strata|, either as $1 \times $36mers or $2 \times $36mers, depending on the dataset. 

As an initial step, Hi-C sequencing reads from all libraries were trimmed of adapter sequences, pooled together, and processed against the previously published \textit{B. minutum} assembly \cite{Shoguchi2013} using the Juicer pipeline \cite{Durand2016a} for analyzing Hi-C datasets (version 1.8.9 of Juicer Tools). 

The resulting Hi-C matrices were then used as input to the 3D DNA pipeline \cite{Dudchenko2017} for automated scaffolding with the following parameters: \verb|--editor-coarse-resolution| \verb|5000| \verb|--editor-coarse-region| \verb|5000| \verb|--polisher-input-size| \verb|100000| \verb|--polisher-coarse-resolution| \verb|1000| \newline \verb|--polisher-coarse-region| \verb|300000| \newline  \verb|--splitter-input-size| \verb|100000| \newline  \verb|--splitter-coarse-resolution| \verb|5000| \newline \verb|--splitter-coarse-region| \verb|300000| \verb|--sort-output| \verb|--build-gapped-map| \verb|-r 10| \verb|-i 5000|.

Manual correction of obvious assembly and scaffolding errors was then carried out using Juicebox \cite{Durand2016a}.

After finalizing the scaffolding, Hi-C reads were reprocessed against the new assembly using the Juicer pipeline. This was done individually for each library as well as together for the pooled set of reads. 

Data was extracted from the final read matrices using the Juicer suite of tools for Hi-C data analysis.

\subsection*{Identification of Hi-C domains}

Hi-C matrices were first converted to \textit{cool} format using HiCExplorer \cite{Ramirez2018} "hicConvertFormat" with parameters \verb|--inputFormat| \verb|hic| \verb|--outputFormat| \verb|h5| and default resolutions. Subsequent HiCExplorer commands were carried out at 10 kb, 25 kb, and 50 kb resolutions with similar results. Matrices were normalized using "hicNormalize" with parameter \verb|--normalize| \verb|smallest|, and corrected using "hicCorrectMatrix correct" with parameters \verb|--correctionMethod| \verb|KR|. Hi-C domains were computationally identified using the "hicFindTADs" from HiCExplorer with parameter \verb|--correctForMultipleTesting| \verb|fdr|.

\subsection*{RNA-seq datasets}

Approximately $5 \times 10^7$ cells were collected by centrifugation at 100 $g$ for 5 minutes at room temperature. Total RNA was extracted and libraries were constructed for RNA-Seq using the TruSeq RNA Library Prep Kit V2 (Illumina, San Diego, CA, USA) according to the manufacturer protocol. All of the raw sequencing reads are available at Sequence Read Archive (SRA) with accession number SRX7258938.

\subsection*{RNA-seq data analysis}

RNA-seq reads were aligned against the corresponding assemblies using the STAR aligner \cite{Dobin2013} (version 2.5.3a) with the following settings: \verb|--limitSjdbInsertNsj| \verb|10000000| \verb|--outFilterMultimapNmax| \verb|50 \verb|--outFilterMismatchNmax| \verb|999| \newline \verb|--outFilterMismatchNoverReadLmax| \verb|0.04| \newline  \verb|--alignIntronMin| \verb|10|  \verb|--alignIntronMax| \verb|1000000|  \verb|--alignMatesGapMax| \verb|1000000|  \verb|--alignSJoverhangMin| \verb|8|  \verb|--alignSJDBoverhangMin| \verb|1|  \verb|--sjdbScore| \verb|1|  \verb|--twopassMode| \verb|Basic|  \verb|--twopass1readsN| \verb|-1|. As available RNA-seq datasets for \textit{B. minutum} are not strand-specific, the strand orientation of the transcriptome was visualized as follows. Aligned reads were first \textit{de novo} assembled into transcripts and quantified at the transcript level using Stringtie \cite{Pertea2015} (version 1.3.3.b); the orientation of splice junctions serves as a reliable guide for the directionality of these transcripts. Open reading frames (ORFs) were identified for each transcript, and transcripts with ORFs shorter than 60 amino acids were filtered out of the transcript set. Strand-specific genomic tracks were then generated by assigning to each basepair covered by at least one exon in that set the sum of the TPM (Transcript Per Million transcripts) values of all transcripts it is included in.

\subsection*{External Hi-C datasets}

Hi-C data for \textit{Trypanosoma brucei} was obtained from GEO accession GSE118764. 

Hi-C data for \textit{Schizosaccharomyces pombe} was obtained from GEO accession GSE57316.

Hi-C data for \textit{Caulobacter vibrioides} CB15 was obtained from GEO accession GSE45966.

\subsection*{Sequence Analysis}

Topoisomerase and other replication-related proteins were identified in annotated MMETSP transcriptome assemblies using HMMER3.0 \cite{Eddy2011} and the Pfam 27.0 protein domain database \cite{Finn2014} as previously described \cite{Marinov2015}.

\end{multicols}

\clearpage

% \end{document}

\section*{Supplementary Tables}

\begin{small}
\begin{center}
\begin{longtable}{m{11cm}m{2cm}m{2cm}m{2cm}}
\caption[]{Summary of Hi-C datasets used in this study}\\
\hline
Hi-C library & Number raw read pairs & Estimated library complexity & Number Hi-C contacts \\
\hline
\endfirsthead
\multicolumn{4}{c}%
{\tablename\ \thetable\ -- \textit{Continued from previous page}} \\
\hline
Hi-C library & Number raw read pairs & Estimated library complexity & Number Hi-C contacts \\
\hline
\endhead
\hline \multicolumn{4}{r}{\textit{Continued on next page}} \\
\endfoot
\hline
\endlastfoot
L142-SSBO1-HIC & 534,609,924 & 920,112,029   & 220,908,462 \\
L533-SSBO1\_27C\_Hi-C          & 556,089,015 & 1,513,268,498 & 151,618,419 \\
L534-SSBO1\_34C\_Hi-C          & 531,461,453 & 2,971,291,849 & 165,231,965 \\
L1240-SSBO1-$\alpha$\_amanitin-0h-Hi-C & 111,333,226 & 233,525,989 & 34,384,671 \\
% L1241+L1242-SSB01-$\alpha$\_amanitin-16h & 128,072,777 & 495,967,910 & 49,755,212 \\
L1241-SSB01-$\alpha$\_amanitin-16h-Hi-C-rep1 & 60,696,609 & 317,650,525 & 24,238,281 \\
L1242-SSB01-$\alpha$\_amanitin-16h-Hi-C-rep2 & 67,376,168 & 227,736,960 & 25,551,603 \\
% L1243+L1244-SSB01-$\alpha$\_amanitin-24h & 187,913,804 & 265,912,578 & 58,445,663 \\
L1243-SSB01-$\alpha$\_amanitin-24h-Hi-C-rep1 & 81,532,584 & 235,898,386 & 29,748,439 \\
L1244-SSB01-$\alpha$\_amanitin-24h-Hi-C-rep2 & 106,381,220 & 110,607,925 & 28,845,306 \\
% L1245+L1246-SSB01-$\alpha$\_amanitin-48h & 169,163,291 & 277,220,794 & 48,946,415 \\
L1245-SSB01-$\alpha$\_amanitin-48h-Hi-C-rep1 & 90,180,763 & 155,046,434 & 27,045,343 \\
L1246-SSB01-$\alpha$\_amanitin-48h-Hi-C-rep2 & 78,982,528 & 152,703,652 & 22,153,117 \\
L1247-SSB01-$\alpha$\_amanitin\_high-48h-Hi-C & 110,015,013 & 157,350,902 & 28,138,017 \\
L1332-SSB01-$\alpha$\_amanitin-0h-Hi-C-technical\_rep & 117,543,007 & 182,213,300 & 34,089,285 \\
L1333-SSB01-$\alpha$\_amanitin-48h-Hi-C-rep1-technical\_rep & 117,821,773 & 82,740,021 & 23,654,760 \\
L1334-SSB01-$\alpha$\_amanitin\_high-48h-Hi-C-technical\_rep & 95,662,202 & 164,149,035 & 23,944,231 \\
% L1335-SSB01-$\alpha$\_amanitin\_high-0h-Hi-C-second\_time\_course & 140,912,027 & 31,287,862 & 11,633,098 \\
L1336-SSB01-$\alpha$\_amanitin\_high-24h-Hi-C-second\_time\_course & 58,747,402 & 103,174,104 & 15,663,160 \\
L1337-SSB01-$\alpha$\_amanitin\_high-48h-Hi-C-second\_time\_course & 83,691,617 & 62,658,394 & 14,523,464 \\
L1344-SSB01-$\alpha$\_amanitin/triptolide\_0h\_NT-Hi-C & 79,383,186 & 208,157,102 & 23,592,335 \\
L1346-SSB01-triptolide\_8h\_normal\_dose-Hi-C & 81,731,190 & 193,514,340 & 22,700,096 \\
L1347-SSB01-triptolide\_8h\_high\_dose-Hi-C & 112,753,865 & 187,235,670 & 28,552,855 \\
L1348-SSB01-Triptolide\_24h NT-Hi-C	& 52,148,987 & 166,057,825 & 15,674,551 \\
L1349-SSB01-triptolide\_24h\_normal\_dose-Hi-C & 132,715,807 & 206,778,720 & 36,745,591 \\
L1350-SSB01-triptolide\_24h\_high\_dose-Hi-C & 98,429,444 & 265,027,975 & 32,121,298 \\
L1351-SSB01-Triptolide\_48h NT-Hi-C	& 96,846,551 & 240,797,245 & 28,296,251 \\
L1352-SSB01-triptolide\_48h\_normal\_dose-Hi-C & 85,347,611 & 255,500,603 & 25,051,605 \\
L1353-SSB01-triptolide\_48h\_high\_dose-Hi-C & 99,978,207 & 215,504,692 & 26,572,806
\label{TableS1}
\end{longtable}
\end{center}
\end{small}

\clearpage

\begin{small}
\begin{center}
\begin{longtable}{m{2.5cm}m{7cm}m{0.5cm}m{0.5cm}m{0.5cm}m{0.5cm}m{0.7cm}m{0.5cm}m{0.5cm}m{0.5cm}m{0.5cm}}
\caption[]{Inventory of topoisomerases and some other proteins involved in DNA replication in dinoflagellates and other eukaryotes as annotated by transcriptome assemblies in the MMETSP databses}\\
\hline
clade & species & TOP1 & TOP2 & TOP3 & MCM & PCNA & RPA1 & RPA2 & RPA3 & RFC1 \\
\hline
\endfirsthead
\multicolumn{11}{c}%
{\tablename\ \thetable\ -- \textit{Continued from previous page}} \\
\hline
clade & species & TOP1 & TOP2 & TOP3 & MCM & PCNA & RPA1 & RPA2 & RPA3 & RFC1 \\
\hline
\endhead
\hline \multicolumn{11}{r}{\textit{Continued on next page}} \\
\endfoot
\hline
\endlastfoot
Amoebozoa & \textit{Stereomyxa ramosa} Chinc5 & 1 & 2 & 2 & 6 & 2 & 3 & 0 & 2 & 1 \\
Amoebozoa & \textit{Vexillifera} sp. DIVA3 564 2 & 1 & 2 & 2 & 7 & 1 & 2 & 0 & 0 & 1 \\
Apicomplexa & \textit{Lankesteria abbottii} Grappler Inlet BC & 1 & 1 & 0 & 12 & 5 & 1 & 0 & 0 & 1 \\
Bicosoecid & Bicosoecid sp ms1 & 1 & 0 & 0 & 3 & 1 & 1 & 1 & 1 & 0 \\
Bicosoecid & \textit{Cafeteria roenbergensis} E4 10 & 1 & 0 & 2 & 6 & 1 & 0 & 0 & 1 & 0 \\
Bicosoecid & \textit{Cafeteria} sp. Caron Lab Isolate & 1 & 1 & 4 & 15 & 1 & 1 & 0 & 1 & 1 \\
Bolidophyte & \textit{Bolidomonas pacifica} CCMP 1866 & 2 & 5 & 7 & 8 & 1 & 1 & 0 & 0 & 1 \\
Chlorarachniophyte & \textit{Bigelowiella natans} CCMP1258.1 & 1 & 1 & 9 & 3 & 1 & 4 & 1 & 0 & 0 \\
Chlorarachniophyte & \textit{Bigelowiella natans} CCMP1259 & 1 & 1 & 6 & 7 & 1 & 4 & 1 & 0 & 1 \\
Chlorarachniophyte & \textit{Bigelowiella natans} CCMP 2755 & 0 & 0 & 4 & 5 & 1 & 4 & 1 & 0 & 1 \\
Chlorarachniophyte & \textit{Bigelowiella natans} CCMP623 & 1 & 3 & 7 & 9 & 1 & 2 & 1 & 0 & 1 \\
Chlorarachniophyte & \textit{Chlorarachnion reptans} CCCM449 & 2 & 4 & 8 & 11 & 2 & 3 & 1 & 0 & 1 \\
Chlorarachniophyte & \textit{Lotharella amoebiformis} CCMP2058 & 2 & 6 & 5 & 10 & 1 & 4 & 1 & 0 & 1 \\
Chlorarachniophyte & \textit{Lotharella globosa} CCCM811 & 1 & 2 & 1 & 0 & 1 & 1 & 1 & 1 & 1 \\
Chlorarachniophyte & \textit{Lotharella oceanica} CCMP622 & 1 & 0 & 0 & 1 & 1 & 2 & 1 & 1 & 1 \\
Chlorarachniophyte & \textit{Norrisiella sphaerica} BC52 & 1 & 0 & 3 & 0 & 1 & 2 & 1 & 1 & 0 \\
Chlorarachniophyte & \textit{Partenskyella glossopodia} RCC365 & 1 & 2 & 1 & 7 & 1 & 3 & 1 & 2 & 1 \\
Chlorophyte & \textit{Bathycoccus prasinos} CCMP1898 & 1 & 2 & 3 & 9 & 1 & 2 & 0 & 0 & 0 \\
Chlorophyte & \textit{Bathycoccus prasinos} RCC716 & 1 & 2 & 3 & 7 & 1 & 3 & 0 & 0 & 1 \\
Chlorophyte & \textit{Chlamydomonas} cf sp CCMP681 & 1 & 0 & 0 & 5 & 2 & 1 & 0 & 0 & 1 \\
Chlorophyte & \textit{Crustomastix stigmata} CCMP3273 & 1 & 2 & 4 & 10 & 1 & 1 & 1 & 0 & 1 \\
Chlorophyte & \textit{Cyanoptyche gloeocystis} SAG4.97 & 1 & 0 & 0 & 4 & 1 & 1 & 1 & 0 & 0 \\
Chlorophyte & \textit{Dolichomastix tenuilepis} CCMP3274 & 1 & 1 & 3 & 1 & 2 & 1 & 0 & 1 & 1 \\
Chlorophyte & \textit{Dunaliella tertiolecta} CCMP1320 & 1 & 2 & 3 & 10 & 1 & 2 & 0 & 1 & 1 \\
Chlorophyte & \textit{Mantoniella antarctica} SL 175 & 1 & 8 & 4 & 13 & 1 & 2 & 2 & 1 & 1 \\
Chlorophyte & \textit{Mantoniella} sp CCMP1436 & 1 & 2 & 1 & 2 & 1 & 1 & 1 & 1 & 1 \\
Chlorophyte & \textit{Micromonas} sp CCMP2099 & 1 & 2 & 2 & 9 & 1 & 2 & 0 & 1 & 1 \\
Chlorophyte & \textit{Micromonas} sp NEPCC29 & 1 & 2 & 3 & 7 & 1 & 2 & 0 & 1 & 1 \\
Chlorophyte & \textit{Micromonas} sp RCC472 & 1 & 2 & 2 & 7 & 1 & 2 & 1 & 0 & 1 \\
Chlorophyte & \textit{Nephroselmis pyriformis} CCMP717 & 1 & 4 & 8 & 10 & 1 & 2 & 0 & 1 & 1 \\
Chlorophyte & \textit{Picochlorum oklahomensis} CCMP2329 & 1 & 2 & 2 & 6 & 2 & 2 & 1 & 0 & 1 \\
Chlorophyte & \textit{Picochlorum} sp. RCC944 & 1 & 1 & 2 & 6 & 1 & 2 & 0 & 2 & 1 \\
Chlorophyte & \textit{Picocystis salinarum} CCMP1897 & 1 & 2 & 1 & 8 & 2 & 2 & 1 & 2 & 1 \\
Chlorophyte & \textit{Polytomella parva} SAG 63 3 & 1 & 5 & 3 & 18 & 2 & 3 & 0 & 0 & 1 \\
Chlorophyte & \textit{Prasinoderma coloniale} CCMP1413 & 1 & 2 & 0 & 2 & 1 & 1 & 0 & 0 & 0 \\
Chlorophyte & \textit{Prasinoderma singularis} RCC927 & 1 & 1 & 1 & 7 & 1 & 1 & 0 & 1 & 1 \\
Chlorophyte & \textit{Pterosperma} sp. CCMP1384 & 1 & 0 & 0 & 3 & 1 & 1 & 1 & 1 & 1 \\
Chlorophyte & \textit{Pycnococcus provasolii} RCC2336 & 1 & 1 & 0 & 9 & 1 & 1 & 0 & 0 & 1 \\
Chlorophyte & \textit{Pycnococcus provasolii} RCC931 & 1 & 0 & 0 & 7 & 1 & 1 & 0 & 0 & 1 \\
Chlorophyte & \textit{Pyramimonas parkeae} CCMP726 & 1 & 0 & 4 & 7 & 1 & 2 & 1 & 1 & 1 \\
Chlorophyte & \textit{Stichococcus} sp RCC1054 & 1 & 1 & 1 & 8 & 1 & 1 & 0 & 0 & 1 \\
Chlorophyte & \textit{Tetraselmis chuii} PLY429 & 2 & 0 & 0 & 0 & 0 & 2 & 0 & 1 & 2 \\
Chlorophyte & \textit{Tetraselmis striata} LANL1001 & 1 & 4 & 4 & 11 & 1 & 2 & 0 & 1 & 1 \\
Choanoflagellata & \textit{Acanthoeca} like sp 10tr & 1 & 3 & 4 & 10 & 1 & 1 & 0 & 1 & 1 \\
Chromerida & \textit{Chromera velia} CCMP2878 & 1 & 1 & 3 & 10 & 2 & 2 & 0 & 0 & 1 \\
Chromerida & \textit{Vitrella brassicaformis} CCMP3346 & 1 & 1 & 2 & 9 & 2 & 1 & 0 & 0 & 1 \\
Chrysophyte & \textit{Chromulina nebulosa} UTEXLB2642 & 1 & 1 & 1 & 2 & 1 & 1 & 0 & 0 & 1 \\
Chrysophyte & \textit{Dinobryon} sp UTEXLB2267 & 1 & 3 & 0 & 8 & 1 & 1 & 0 & 0 & 1 \\
Chrysophyte & \textit{Mallomonas} Sp CCMP3275 & 1 & 2 & 1 & 9 & 1 & 1 & 0 & 1 & 1 \\
Chrysophyte & \textit{Ochromonas} sp CCMP1393 & 1 & 2 & 2 & 7 & 1 & 1 & 0 & 0 & 1 \\
Chrysophyte & \textit{Paraphysomonas bandaiensis} Caron Lab Isolate & 1 & 2 & 3 & 9 & 2 & 1 & 1 & 1 & 1 \\
Chrysophyte & \textit{Paraphysomonas imperforata} PA2 & 0 & 1 & 3 & 6 & 1 & 1 & 1 & 1 & 1 \\
Chrysophyte & \textit{Pelagococcus subviridis} CCMP1429 & 1 & 1 & 2 & 11 & 1 & 0 & 0 & 0 & 1 \\
Chrysophyte & \textit{Spumella elongata} CCAP 955 1 & 1 & 1 & 3 & 10 & 4 & 3 & 0 & 1 & 1 \\
Ciliate & \textit{Aristerostoma} sp. ATCC 50986 & 2 & 1 & 1 & 0 & 2 & 1 & 0 & 0 & 2 \\
Ciliate & \textit{Blepharisma japonicum} Stock R1072 & 0 & 0 & 0 & 7 & 4 & 1 & 0 & 0 & 0 \\
Ciliate & \textit{Climacostomum virens} Stock W 24 & 1 & 2 & 2 & 9 & 3 & 1 & 0 & 0 & 3 \\
Ciliate & \textit{Condylostoma magnum} COL2 & 0 & 0 & 0 & 2 & 0 & 0 & 0 & 0 & 0 \\
Ciliate & \textit{Euplotes focardii} TN1 & 1 & 0 & 0 & 5 & 2 & 1 & 0 & 2 & 0 \\
Ciliate & \textit{Euplotes harpa} FSP1.4 & 2 & 0 & 5 & 3 & 1 & 0 & 0 & 1 & 0 \\
Ciliate & \textit{Fabrea salina} Unknown & 1 & 1 & 3 & 7 & 2 & 3 & 0 & 0 & 2 \\
Ciliate & \textit{Favella taraikaensis} FeNarragansettBay & 0 & 1 & 2 & 7 & 3 & 0 & 0 & 0 & 0 \\
Ciliate & \textit{Litonotus pictus} P1 & 1 & 1 & 2 & 0 & 0 & 0 & 0 & 0 & 0 \\
Ciliate & \textit{Mesodinium pulex} SPMC105 & 2 & 13 & 2 & 16 & 9 & 4 & 0 & 0 & 6 \\
Ciliate & \textit{Myrionecta rubra} CCMP2563 & 0 & 1 & 4 & 11 & 1 & 1 & 0 & 1 & 0 \\
Ciliate & \textit{Platyophrya macrostoma} WH & 4 & 4 & 4 & 23 & 4 & 6 & 0 & 0 & 3 \\
Ciliate & \textit{Protocruzia adherens} Boccale & 3 & 1 & 0 & 9 & 3 & 3 & 0 & 0 & 1 \\
Ciliate & \textit{Pseudokeronopsis} sp. OXSARD2 & 1 & 1 & 1 & 6 & 1 & 0 & 0 & 1 & 1 \\
Ciliate & \textit{Strombidinopsis acuminatum} SPMC142 & 2 & 6 & 0 & 32 & 10 & 5 & 0 & 0 & 0 \\
Ciliate & \textit{Strombidinopsis} sp. SopsisLIS2011 & 1 & 0 & 0 & 8 & 3 & 2 & 0 & 0 & 0 \\
Ciliate & \textit{Strombidium} inclinatum S3 & 1 & 1 & 2 & 8 & 1 & 1 & 0 & 0 & 1 \\
Ciliate & \textit{Strombidium rassoulzadegani} ras09 & 1 & 0 & 1 & 6 & 1 & 1 & 0 & 1 & 0 \\
Ciliate & \textit{Tiarina fusus} LIS & 1 & 7 & 3 & 16 & 3 & 4 & 2 & 1 & 1 \\
Cryptophyte & \textit{Chroomonas mesostigmatica} cf CCMP1168 & 1 & 5 & 4 & 8 & 1 & 2 & 2 & 0 & 1 \\
Cryptophyte & \textit{Cryptomonas curvata} CCAP979 52 & 2 & 0 & 2 & 0 & 1 & 1 & 0 & 1 & 0 \\
Cryptophyte & \textit{Cryptomonas paramecium} CCAP977 2a & 3 & 2 & 2 & 5 & 1 & 1 & 0 & 0 & 1 \\
Cryptophyte & \textit{Geminigera cryophila} CCMP2564 & 2 & 1 & 5 & 11 & 1 & 2 & 0 & 1 & 2 \\
Cryptophyte & \textit{Geminigera} sp. Caron Lab Isolate & 1 & 3 & 5 & 18 & 1 & 5 & 0 & 1 & 1 \\
Cryptophyte & \textit{Goniomonas pacifica} CCMP1869 & 8 & 4 & 4 & 12 & 1 & 5 & 1 & 3 & 7 \\
Cryptophyte & \textit{Guillardia theta} CCMP 2712 & 1 & 0 & 2 & 3 & 1 & 1 & 0 & 1 & 0 \\
Cryptophyte & \textit{Hemiselmis andersenii} CCMP644 & 1 & 2 & 5 & 12 & 1 & 2 & 0 & 1 & 1 \\
Cryptophyte & \textit{Hemiselmis rufescens} PCC563 & 1 & 0 & 3 & 7 & 1 & 1 & 1 & 1 & 1 \\
Cryptophyte & \textit{Hemiselmis tepida} CCMP443 & 3 & 2 & 0 & 3 & 1 & 1 & 1 & 1 & 1 \\
Cryptophyte & \textit{Hemiselmis viresens} PCC157 & 1 & 0 & 0 & 7 & 1 & 1 & 0 & 1 & 0 \\
Cryptophyte & \textit{Palpitomonas bilix} NIES 2562 & 0 & 1 & 2 & 13 & 4 & 3 & 0 & 1 & 3 \\
Cryptophyte & \textit{Proteomonas sulcata} CCMP704 & 0 & 1 & 0 & 3 & 1 & 1 & 0 & 0 & 1 \\
Cryptophyte & \textit{Rhodomonas lens} RHODO & 2 & 3 & 2 & 2 & 2 & 2 & 0 & 1 & 0 \\
Cryptophyte & \textit{Rhodomonas} sp. CCMP768 & 1 & 0 & 1 & 0 & 1 & 1 & 0 & 0 & 0 \\
Diatome & \textit{Amphiprora} sp. & 1 & 4 & 3 & 9 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Amphora coffeaeformis} CCMP127 & 1 & 1 & 0 & 4 & 1 & 1 & 0 & 0 & 0 \\
Diatome & \textit{Asterionellopsis glacialis} CCMP134 & 1 & 7 & 1 & 10 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Astrosyne radiata} 13vi08 1A & 1 & 8 & 3 & 6 & 3 & 2 & 0 & 0 & 1 \\
Diatome & \textit{Attheya septentrionalis} CCMP2084 & 1 & 2 & 0 & 9 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Aulacoseira subarctica} CCAP 1002 5 & 1 & 2 & 3 & 8 & 2 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Chaetoceros affinis} CCMP159 & 1 & 3 & 1 & 8 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Chaetoceros curvisetus} & 1 & 4 & 4 & 6 & 1 & 3 & 0 & 0 & 1 \\
Diatome & \textit{Chaetoceros debilis} MM31A\_1 & 1 & 3 & 1 & 12 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Chaetoceros neogracile} CCMP1317 & 1 & 9 & 3 & 10 & 1 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Coscinodiscus wailesii} CCMP2513 & 1 & 3 & 6 & 10 & 1 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Craspedostauros australis} CCMP3328 & 1 & 0 & 0 & 4 & 0 & 1 & 0 & 0 & 0 \\
Diatome & \textit{Cyclophora tenuis} ECT3854 & 1 & 1 & 0 & 3 & 1 & 1 & 0 & 0 & 0 \\
Diatome & \textit{Cyclotella meneghiniana} CCMP 338 & 1 & 4 & 3 & 8 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Cylindrotheca closterium} KMMCC:B 181 & 3 & 7 & 3 & 14 & 1 & 2 & 0 & 0 & 1 \\
Diatome & \textit{Dactyliosolen fragilissimus} Unknown & 1 & 3 & 3 & 8 & 1 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Ditylum brightwellii} GSO103 & 1 & 4 & 3 & 11 & 1 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Ditylum brightwellii} GSO104 & 1 & 4 & 5 & 10 & 1 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Ditylum brightwellii} GSO105 & 1 & 2 & 3 & 11 & 2 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Entomoneis} sp. CCMP2396 & 0 & 1 & 0 & 0 & 1 & 1 & 0 & 0 & 0 \\
Diatome & \textit{Eucampia antarctica} CCMP1452 & 1 & 3 & 0 & 5 & 1 & 1 & 1 & 1 & 1 \\
Diatome & \textit{Extubocellulus spinifer} CCMP396 & 1 & 4 & 10 & 13 & 2 & 5 & 3 & 1 & 2 \\
Diatome & \textit{Fragilariopsis kerguelensis} L2\_C3 & 1 & 3 & 3 & 11 & 1 & 1 & 2 & 0 & 1 \\
Diatome & \textit{Fragilariopsis kerguelensis} L26\_C5 & 1 & 3 & 5 & 22 & 1 & 1 & 3 & 0 & 1 \\
Diatome & \textit{Grammatophora oceanica} CCMP 410 & 1 & 1 & 3 & 5 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Helicotheca tamensis} CCMP826 & 0 & 1 & 0 & 1 & 1 & 1 & 0 & 1 & 0 \\
Diatome & \textit{Leptocylindrus danicus} var. apora B651 & 3 & 5 & 3 & 0 & 3 & 2 & 0 & 1 & 1 \\
Diatome & \textit{Leptocylindrus danicus} var. danicus B650 & 3 & 11 & 3 & 19 & 1 & 1 & 0 & 1 & 2 \\
Diatome & \textit{Licmophora paradoxa} CCMP2313 & 1 & 1 & 3 & 7 & 1 & 2 & 0 & 0 & 1 \\
Diatome & \textit{Minutocellus polymorphus} CCMP3303 & 0 & 0 & 0 & 3 & 1 & 1 & 1 & 1 & 0 \\
Diatome & \textit{Minutocellus polymorphus} NH13 & 2 & 8 & 7 & 21 & 1 & 0 & 1 & 0 & 3 \\
Diatome & \textit{Minutocellus polymorphus} RCC2270 & 1 & 2 & 1 & 7 & 1 & 1 & 1 & 1 & 1 \\
Diatome & \textit{Nitzschia punctata} CCMP561 & 1 & 2 & 2 & 9 & 1 & 1 & 1 & 1 & 1 \\
Diatome & \textit{Odontella aurita} isolate 1302 5 & 1 & 3 & 7 & 11 & 2 & 2 & 1 & 1 & 1 \\
Diatome & \textit{Odontella sinensis} Grunow 1884 & 1 & 3 & 0 & 2 & 1 & 1 & 1 & 1 & 1 \\
Diatome & \textit{Proboscia alata} PI\_D3 & 1 & 7 & 2 & 21 & 1 & 1 & 2 & 0 & 1 \\
Diatome & \textit{Pseudo-nitzschia australis} 10249\_10\_AB & 1 & 3 & 4 & 8 & 1 & 1 & 1 & 0 & 1 \\
Diatome & \textit{Pseudo-nitzschia fradulenta} WWA7 & 2 & 11 & 6 & 24 & 4 & 5 & 0 & 0 & 3 \\
Diatome & \textit{Rhizosolenia setigera} CCMP 1694 & 1 & 7 & 4 & 18 & 1 & 2 & 0 & 0 & 2 \\
Diatome & \textit{Skeletonema dohrnii} SkelB & 1 & 2 & 0 & 14 & 1 & 1 & 2 & 1 & 1 \\
Diatome & \textit{Skeletonema marinoi} SkelA & 1 & 1 & 2 & 7 & 1 & 1 & 2 & 0 & 1 \\
Diatome & \textit{Skeletonema menzelii} CCMP793 & 1 & 4 & 4 & 8 & 1 & 1 & 2 & 0 & 1 \\
Diatome & \textit{Stauroneis constricta} CCMP1120 & 1 & 0 & 1 & 1 & 1 & 1 & 1 & 0 & 0 \\
Diatome & \textit{Staurosira complex} sp. CCMP2646 & 1 & 3 & 4 & 8 & 1 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Stephanopyxis turris} CCMP 815 & 2 & 0 & 1 & 7 & 3 & 2 & 0 & 1 & 1 \\
Diatome & \textit{Striatella unipunctata} CCMP2910 & 4 & 2 & 1 & 6 & 3 & 0 & 1 & 0 & 2 \\
Diatome & \textit{Synedropsis recta} cf CCMP1620 & 1 & 2 & 0 & 1 & 1 & 1 & 1 & 1 & 0 \\
Diatome & \textit{Thalassionema frauenfeldii} CCMP 1798 & 1 & 5 & 7 & 15 & 1 & 3 & 1 & 1 & 2 \\
Diatome & \textit{Thalassionema nitzschioides} L26\_B & 1 & 3 & 4 & 8 & 1 & 1 & 1 & 1 & 1 \\
Diatome & \textit{Thalassiosira antarctica} CCMP982 & 1 & 4 & 2 & 12 & 1 & 1 & 3 & 1 & 1 \\
Diatome & \textit{Thalassiosira gravida} GMp14c1 & 1 & 1 & 3 & 13 & 1 & 1 & 2 & 1 & 1 \\
Diatome & \textit{Thalassiosira miniscula} CCMP1093 & 1 & 13 & 6 & 10 & 1 & 1 & 2 & 1 & 1 \\
Diatome & \textit{Thalassiosira oceanica} CCMP1005 & 1 & 10 & 1 & 10 & 1 & 1 & 0 & 0 & 1 \\
Diatome & \textit{Thalassiosira rotula} CCMP3096 & 1 & 5 & 3 & 11 & 1 & 1 & 2 & 1 & 1 \\
Diatome & \textit{Thalassiosira rotula} GSO102 & 1 & 3 & 2 & 11 & 1 & 1 & 1 & 1 & 1 \\
Diatome & \textit{Thalassiosira weissflogii} CCMP1010 & 1 & 4 & 1 & 9 & 1 & 0 & 1 & 0 & 1 \\
Diatome & \textit{Thalassiosira weissflogii} CCMP1336 & 1 & 4 & 1 & 8 & 1 & 0 & 1 & 0 & 1 \\
Diatome & \textit{Thalassiothrix antarctica} L6\_D1 & 1 & 2 & 4 & 6 & 1 & 1 & 0 & 1 & 1 \\
Diatome & \textit{Triceratium dubium} CCMP147 & 0 & 1 & 1 & 1 & 1 & 0 & 1 & 1 & 0 \\
Dinoflagellata & \textit{Alexandrium temarense} CCMP1771 & 3 & 18 & 12 & 45 & 18 & 10 & 3 & 4 & 2 \\
Dinoflagellata & \textit{Amphidinium carterae} CCMP1314 & 2 & 5 & 5 & 8 & 2 & 4 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Azadinium spinosum} 3D9 & 1 & 12 & 13 & 35 & 11 & 6 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Brandtodinium nutriculum} RCC3387 & 1 & 13 & 9 & 30 & 21 & 4 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Ceratium fusus} PA161109 & 1 & 15 & 10 & 18 & 12 & 9 & 1 & 1 & 3 \\
Dinoflagellata & \textit{Crypthecodinium cohnii} Seligo & 1 & 6 & 5 & 15 & 2 & 4 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Dinophysis acuminata} DAEP01 & 4 & 15 & 9 & 29 & 13 & 8 & 0 & 0 & 2 \\
Dinoflagellata & \textit{Durinskia baltica} CSIRO\_CS 38 & 2 & 12 & 9 & 18 & 9 & 8 & 0 & 0 & 4 \\
Dinoflagellata & \textit{Gambierdiscus australes} CAWD 149 & 1 & 5 & 0 & 9 & 14 & 6 & 0 & 0 & 2 \\
Dinoflagellata & \textit{Glenodinium foliaceum} CCAP1116\_3 & 2 & 9 & 3 & 23 & 7 & 6 & 0 & 1 & 4 \\
Dinoflagellata & \textit{Gonyaulax spinifera} CCMP409 & 1 & 2 & 0 & 10 & 10 & 8 & 1 & 1 & 1 \\
Dinoflagellata & \textit{Heterocapsa rotundata} SCCAP K 0483 & 2 & 19 & 4 & 12 & 6 & 4 & 0 & 0 & 6 \\
Dinoflagellata & \textit{Heterocapsa triquestra} CCMP 448 & 1 & 8 & 5 & 13 & 5 & 4 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Karenia brevis} CCMP2229 & 1 & 14 & 8 & 10 & 8 & 7 & 0 & 1 & 4 \\
Dinoflagellata & \textit{Karenia brevis} SP1 & 1 & 14 & 13 & 16 & 6 & 8 & 0 & 1 & 4 \\
Dinoflagellata & \textit{Karenia brevis} SP3 & 1 & 12 & 9 & 13 & 8 & 10 & 0 & 1 & 4 \\
Dinoflagellata & \textit{Karenia brevis} Wilson & 1 & 14 & 7 & 14 & 9 & 8 & 0 & 2 & 5 \\
Dinoflagellata & \textit{Karlodinium micrum} CCMP2283 & 2 & 9 & 7 & 46 & 13 & 31 & 2 & 0 & 5 \\
Dinoflagellata & \textit{Kryptoperidinium foliaceum} CCMP1326 & 4 & 14 & 11 & 64 & 16 & 10 & 1 & 0 & 7 \\
Dinoflagellata & \textit{Lingulodinium polyedra} CCMP1738 & 1 & 17 & 8 & 19 & 11 & 11 & 1 & 0 & 3 \\
Dinoflagellata & \textit{Noctiluca scintillans} Unknown & 1 & 7 & 3 & 9 & 1 & 6 & 0 & 1 & 1 \\
Dinoflagellata & \textit{Oxyrrhis marina} & 1 & 2 & 5 & 9 & 7 & 3 & 0 & 1 & 2 \\
Dinoflagellata & \textit{Oxyrrhis marina} CCMP1795 & 0 & 0 & 0 & 0 & 3 & 0 & 0 & 0 & 0 \\
Dinoflagellata & \textit{Oxyrrhis marina} LB1974 & 1 & 2 & 4 & 10 & 4 & 2 & 0 & 0 & 2 \\
Dinoflagellata & \textit{Pelagodinium beii} RCC1491 & 1 & 8 & 2 & 12 & 11 & 4 & 0 & 0 & 4 \\
Dinoflagellata & \textit{Peridinium aciculiferum} PAER\_2 & 1 & 7 & 5 & 11 & 6 & 5 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Polarella glacialis} CCMP 1383 & 1 & 28 & 5 & 23 & 5 & 5 & 0 & 0 & 8 \\
Dinoflagellata & \textit{Prorocentrum minimum} CCMP1329 & 1 & 15 & 6 & 29 & 13 & 6 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Prorocentrum minimum} CCMP2233 & 1 & 14 & 4 & 29 & 12 & 5 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Protoceratium reticulatum} CCCM 535 CCMP 1889 & 2 & 20 & 9 & 18 & 11 & 10 & 0 & 0 & 2 \\
Dinoflagellata & \textit{Pyrodinium bahamense} pbaha01 & 1 & 21 & 8 & 29 & 19 & 11 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Scrippsiella hangoei} like SHHI\_4 & 1 & 8 & 6 & 22 & 6 & 16 & 0 & 2 & 2 \\
Dinoflagellata & \textit{Scrippsiella hangoei} SHTV5 & 1 & 8 & 11 & 14 & 3 & 5 & 0 & 0 & 2 \\
Dinoflagellata & \textit{Scrippsiella trochoidea} CCMP3099 & 1 & 27 & 10 & 38 & 12 & 8 & 1 & 1 & 3 \\
Dinoflagellata & \textit{Symbiodinium kawagutii} CCMP2468 & 0 & 0 & 0 & 0 & 2 & 0 & 0 & 0 & 0 \\
Dinoflagellata & \textit{Symbiodinium} sp. C1 & 1 & 9 & 4 & 9 & 6 & 4 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Symbiodinium} sp. C15 & 1 & 7 & 2 & 12 & 3 & 4 & 1 & 0 & 3 \\
Dinoflagellata & \textit{Symbiodinium} sp. CCMP2430 & 1 & 7 & 2 & 10 & 7 & 4 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Symbiodinium} sp. Mp & 1 & 7 & 3 & 13 & 6 & 3 & 0 & 0 & 3 \\
Dinoflagellata & \textit{Togula jolla} CCCM 725 & 1 & 17 & 3 & 21 & 3 & 6 & 0 & 0 & 4 \\
Discosea & \textit{Mayorella} sp. BSH 02190019 & 1 & 3 & 2 & 5 & 1 & 1 & 0 & 1 & 1 \\
Discosea & \textit{Neoparamoeba aestuarina} SoJaBio B1 5 56 2 & 3 & 3 & 3 & 12 & 3 & 3 & 0 & 1 & 1 \\
Discosea & \textit{Paramoeba atlantica} 621 1   CCAP 1560 9 & 1 & 3 & 2 & 8 & 3 & 2 & 0 & 1 & 1 \\
Discosea & \textit{Pessonella} sp. PRA 29 & 1 & 1 & 3 & 0 & 1 & 5 & 0 & 2 & 3 \\
Discosea & \textit{Stygamoeba regulata} BSH 02190019 & 3 & 8 & 2 & 7 & 2 & 4 & 0 & 0 & 2 \\
Discosea & \textit{Trichosphaerium} sp. Am I 7 wt & 2 & 0 & 0 & 1 & 2 & 3 & 0 & 0 & 2 \\
Eugelnophyta & \textit{Eutreptiella gymnastica} like CCMP1594 & 1 & 1 & 1 & 5 & 2 & 1 & 0 & 1 & 1 \\
Foraminifera & \textit{Ammonia} sp. Unknown & 1 & 1 & 3 & 9 & 5 & 2 & 0 & 1 & 1 \\
Foraminifera & \textit{Elphidium margaritaceum} Unknown & 1 & 1 & 2 & 8 & 3 & 1 & 1 & 0 & 1 \\
Foraminifera & \textit{Rosalina} sp. Unknown & 1 & 0 & 0 & 9 & 5 & 0 & 2 & 0 & 1 \\
Foraminifera & \textit{Sorites} sp. Unknown & 3 & 3 & 0 & 27 & 12 & 3 & 0 & 0 & 2 \\
Fungi & \textit{Debaryomyces hansenii} J26 & 1 & 0 & 0 & 4 & 0 & 0 & 0 & 0 & 1 \\
Glaucophyte & \textit{Gloeochaete witrockiana} SAG46\_84 & 2 & 2 & 3 & 9 & 2 & 2 & 1 & 1 & 1 \\
Haptophyte & \textit{Calcidiscus leptoporus} RCC1130 & 1 & 3 & 0 & 7 & 1 & 1 & 1 & 0 & 1 \\
Haptophyte & \textit{Chrysochromulina brevifilum} UTEX LB 985 & 1 & 2 & 1 & 4 & 1 & 3 & 0 & 1 & 0 \\
Haptophyte & \textit{Chrysochromulina ericina} CCMP281 & 2 & 1 & 0 & 10 & 1 & 3 & 1 & 1 & 2 \\
Haptophyte & \textit{Chrysochromulina polylepis} CCMP1757 & 1 & 3 & 5 & 9 & 1 & 2 & 1 & 1 & 1 \\
Haptophyte & \textit{Chrysoculter rhomboideus} RCC1486 & 1 & 0 & 0 & 9 & 1 & 0 & 0 & 1 & 0 \\
Haptophyte & \textit{Coccolithus pelagicus} ssp \textit{braarudi} PLY182g & 1 & 3 & 0 & 7 & 1 & 2 & 1 & 1 & 0 \\
Haptophyte & \textit{Emiliania huxleyi} 374 & 1 & 2 & 1 & 9 & 1 & 1 & 0 & 0 & 0 \\
Haptophyte & \textit{Emiliania huxleyi} 379 & 1 & 1 & 1 & 0 & 0 & 2 & 0 & 0 & 0 \\
Haptophyte & \textit{Emiliania huxleyi} CCMP370 & 1 & 3 & 5 & 9 & 0 & 2 & 1 & 1 & 1 \\
Haptophyte & \textit{Emiliania huxleyi} PLYM219 & 1 & 3 & 4 & 10 & 0 & 2 & 1 & 1 & 1 \\
Haptophyte & \textit{Exanthemachrysis gayraliae} RCC1523 & 1 & 2 & 0 & 1 & 1 & 1 & 0 & 1 & 1 \\
Haptophyte & \textit{Gephyrocapsa oceanica} RCC1303 & 1 & 3 & 5 & 11 & 1 & 1 & 0 & 0 & 1 \\
Haptophyte & \textit{Imantonia} sp. RCC918 & 3 & 1 & 1 & 4 & 2 & 1 & 1 & 1 & 0 \\
Haptophyte & \textit{Isochrysis galbana} CCMP1323 & 2 & 5 & 6 & 13 & 2 & 3 & 1 & 0 & 2 \\
Haptophyte & \textit{Isochrysis} sp. CCMP1244 & 1 & 2 & 5 & 11 & 1 & 1 & 0 & 1 & 1 \\
Haptophyte & \textit{Isochrysis} sp. CCMP1324 & 1 & 2 & 0 & 12 & 1 & 2 & 1 & 0 & 1 \\
Haptophyte & \textit{Pavlova} sp. CCMP459 & 1 & 2 & 1 & 6 & 2 & 1 & 2 & 1 & 1 \\
Haptophyte & \textit{Phaeocystis antarctica} Caron Lab Isolate & 3 & 7 & 2 & 12 & 1 & 3 & 2 & 0 & 2 \\
Haptophyte & \textit{Phaeocystis} sp. CCMP2710 & 1 & 0 & 1 & 2 & 1 & 1 & 1 & 1 & 1 \\
Haptophyte & \textit{Pleurochrysis carterae} CCMP645 & 3 & 2 & 1 & 7 & 1 & 2 & 1 & 1 & 1 \\
Haptophyte & \textit{Prymnesium parvum} Texoma1 & 1 & 6 & 4 & 1 & 1 & 2 & 1 & 1 & 1 \\
Haptophyte & \textit{Scyphosphaera apsteinii} RCC1455 & 1 & 3 & 1 & 7 & 1 & 2 & 1 & 0 & 1 \\
Heterolobosea & \textit{Percolomonas cosmopolitus} AE 1 ATCC 50343 & 1 & 4 & 2 & 9 & 2 & 2 & 0 & 0 & 1 \\
Heterolobosea & \textit{Percolomonas cosmopolitus} WS & 1 & 3 & 1 & 12 & 1 & 2 & 0 & 0 & 3 \\
Khakista & \textit{Corethron pennatum} L29A3 & 2 & 5 & 5 & 16 & 1 & 1 & 1 & 0 & 1 \\
Khakista & \textit{Detonula confervacea} CCMP 353 & 1 & 3 & 2 & 9 & 1 & 1 & 2 & 1 & 1 \\
Kinetoplastida & \textit{Neobodo designis} CCAP 1951 1 & 1 & 1 & 4 & 8 & 1 & 1 & 0 & 0 & 1 \\
Labyrinthulida & \textit{Aplanochytrium} sp. PBS07 & 1 & 2 & 1 & 3 & 1 & 1 & 1 & 2 & 1 \\
Labyrinthulida & \textit{Aplanochytrium stocchinoi} GSBS06 & 1 & 2 & 0 & 7 & 1 & 1 & 1 & 1 & 1 \\
Pelagophyte & \textit{Aureococcus anophagefferens} CCMP1850 & 6 & 2 & 3 & 45 & 1 & 2 & 0 & 0 & 1 \\
Pelagophyte & \textit{Aureoumbra lagunensis} CCMP1510 & 1 & 2 & 2 & 9 & 1 & 2 & 1 & 0 & 1 \\
Pelagophyte & \textit{Chrysocystis fragilis} CCMP3189 & 2 & 0 & 2 & 6 & 1 & 1 & 1 & 0 & 1 \\
Pelagophyte & \textit{Chrysoreinhardia} sp. CCMP2950 & 1 & 2 & 1 & 5 & 0 & 1 & 0 & 0 & 1 \\
Pelagophyte & \textit{Chrysoreinhardia} sp. CCMP3193 & 1 & 3 & 2 & 10 & 1 & 2 & 1 & 0 & 1 \\
Pelagophyte & \textit{Pelagomonas calceolata} CCMP1756 & 1 & 2 & 1 & 9 & 1 & 1 & 2 & 0 & 1 \\
Pelagophyte & \textit{Sarcinochrysis} sp. CCMP770 & 0 & 0 & 0 & 2 & 1 & 1 & 1 & 1 & 0 \\
Perkinsid & \textit{Perkinsus chesapeaki} ATCC\_PRA\_65 & 2 & 0 & 0 & 0 & 0 & 0 & 0 & 0 & 0 \\
Perkinsid & \textit{Perkinsus marinus} ATCC50439 & 1 & 0 & 0 & 1 & 2 & 0 & 0 & 0 & 0 \\
Pinguiophyte & \textit{Phaeomonas parva} CCMP2877 & 1 & 3 & 1 & 5 & 3 & 1 & 0 & 1 & 0 \\
Pinguiophyte & \textit{Pinguiococcus pyrenoidosus} CCMP2078 & 1 & 2 & 3 & 0 & 1 & 1 & 0 & 1 & 0 \\
Raphidophyte & \textit{Chattonella subsalsa} CCMP2191 & 1 & 3 & 0 & 5 & 1 & 1 & 1 & 0 & 1 \\
Raphidophyte & \textit{Fibrocapsa japonica} CCMP1661 & 0 & 1 & 1 & 5 & 1 & 1 & 0 & 1 & 0 \\
Raphidophyte & \textit{Heterosigma akashiwo} CCMP2393 & 1 & 4 & 2 & 11 & 2 & 1 & 0 & 1 & 1 \\
Raphidophyte & \textit{Heterosigma akashiwo} CCMP3107 & 1 & 7 & 2 & 0 & 1 & 1 & 0 & 0 & 0 \\
Raphidophyte & \textit{Heterosigma akashiwo} CCMP452 & 0 & 1 & 0 & 4 & 1 & 1 & 0 & 0 & 0 \\
Raphidophyte & \textit{Heterosigma akashiwo} NB & 1 & 6 & 1 & 8 & 1 & 1 & 0 & 1 & 1 \\
Rhodophyte  & \textit{Compsopogon coeruleus} SAG 36.94 & 1 & 3 & 2 & 11 & 1 & 1 & 0 & 0 & 1 \\
Rhodophyte  & \textit{Erythrolobus australicus} CCMP3124 & 1 & 2 & 3 & 0 & 1 & 1 & 0 & 1 & 1 \\
Rhodophyte  & \textit{Erythrolobus madagascarensis} CCMP3276 & 1 & 1 & 1 & 3 & 1 & 2 & 0 & 1 & 0 \\
Rhodophyte  & \textit{Madagascaria erythrocladiodes} CCMP3234 & 3 & 4 & 5 & 12 & 1 & 2 & 0 & 1 & 2 \\
Rhodophyte  & \textit{Porphyridium aerugineum} SAG 1380 2 & 2 & 1 & 2 & 5 & 1 & 2 & 1 & 0 & 1 \\
Rhodophyte  & \textit{Rhodella maculata} CCMP736 & 1 & 3 & 3 & 12 & 1 & 1 & 0 & 0 & 1 \\
Rhodophyte  & \textit{Rhodosorus marinus} CCMP 769 & 1 & 8 & 6 & 17 & 0 & 3 & 0 & 0 & 2 \\
Rhodophyte  & \textit{Timspurckia oligopyrenoides} CCMP3278 & 1 & 2 & 4 & 6 & 1 & 2 & 1 & 1 & 1 \\
Silicoflagellates & \textit{Dictyocha speculum} CCMP1381 & 1 & 4 & 2 & 9 & 1 & 2 & 1 & 1 & 1 \\
Silicoflagellates & \textit{Pseudopedinella elastica} CCMP716 & 1 & 5 & 6 & 9 & 1 & 1 & 1 & 1 & 1 \\
Silicoflagellates & \textit{Pteridomonas danica} PT & 1 & 1 & 1 & 2 & 1 & 1 & 1 & 1 & 0 \\
Silicoflagellates & \textit{Rhizochromulina marina} cf CCMP1243 & 1 & 5 & 2 & 8 & 2 & 2 & 1 & 1 & 1 \\
Synchromophyceae & \textit{Synchroma pusillum} CCMP3072 & 1 & 0 & 1 & 3 & 3 & 1 & 0 & 1 & 1 \\
Syndinian & \textit{Amoebophrya} sp. Ameob2 & 2 & 8 & 1 & 13 & 0 & 1 & 0 & 0 & 0 \\
Thraustochytrid & \textit{Aurantiochytrium limacinum} ATCCMYA1381 & 1 & 3 & 2 & 9 & 1 & 1 & 0 & 1 & 1 \\
Thraustochytrid & \textit{Schizochytrium aggregatum} ATCC28209 & 1 & 1 & 1 & 4 & 1 & 1 & 0 & 0 & 1 \\
Thraustochytrid & \textit{Thraustochytrium} sp. LLF1b & 1 & 2 & 1 & 9 & 1 & 1 & 0 & 1 & 1 \\
Tubulinid & \textit{Filamoeba nolandi} NC AS 23 1 & 2 & 4 & 1 & 13 & 0 & 3 & 1 & 0 & 1 \\
Tubulinid & \textit{Sexangularia} sp. ATCC50979 & 0 & 6 & 7 & 14 & 2 & 2 & 1 & 0 & 3 \\
Vanellinid & \textit{Vannella robusta} DIVA3 518 3 11 1 6 & 1 & 2 & 3 & 6 & 1 & 2 & 1 & 1 & 1 \\
Vanellinid & \textit{Vannella} sp. DIVA3 517 6 12 & 6 & 6 & 9 & 13 & 1 & 1 & 0 & 1 & 1 \\
Xantophyte & \textit{Vaucheria litorea} CCMP2940 & 1 & 2 & 0 & 6 & 1 & 1 & 0 & 1 & 1 \\
\label{TableS2}
\end{longtable}
\end{center}
\end{small}

\clearpage

\section*{Supplementary Figures}

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=10cm]{FigS1-V2.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Cumulative distribution of scaffolds and pseudochromosome sizes before and after Hi-C scaffolding of the draft \textit{Breviolum}/\textit{Symbiodinium minutum} assembly \cite{Shoguchi2013}}. 3D DNA\cite{Dudchenko2017} scaffolding of the assembly results in 91 major pseudochromosomes $\geq$500kb encompassing $\sim$94\% of the assembled sequence.
}
\label{FigS1}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=16cm]{FigS2-500KB-resolution.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Broad-level bipartite to tripartite topological structure of dinoflagellate}. Shown are 1Mbp-resolution KR-normalized\cite{KR} Hi-C matrices for four of the \textit{B. minutum} pseudochromosomes.
}
\label{FigS2}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS3-scaffold17.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 17.
}
\label{FigS3}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS4-scaffold18.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 18.
}
\label{FigS4}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS5-scaffold21.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 21.
}
\label{FigS5}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS6-scaffold26.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 26.
}
\label{FigS6}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS8-scaffold32.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 32.
}
\label{FigS8}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS9-scaffold36.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 36.
}
\label{FigS9}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS10-scaffold71.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 71.
}
\label{FigS10}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS11-scaffold77.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 77.
}
\label{FigS11}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS12-scaffold78.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 78.
}
\label{FigS12}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS13-scaffold88.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 88.
}
\label{FigS13}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS14-scaffold89.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf The topological domain organization of dinoflagellate chromosomes is related to polycistronic gene array orientation}. Shown is the 5kb-resolution KR-normalized Hi-C map together with strand-specific RNA expression levels for pseudochromosome 89.
}
\label{FigS14}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS31-Caulobacter-GSM1120448.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Topological structure of the \textit{Caulobacter crescentus} CB15 genome}. Shown is the KR-normalized 5-kb resolution maps for the whole \textit{Caulobacter} chromosome (GEO accession GSM1120448).
\label{FigS31}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS32-pombe.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Topological structure of the \textit{Schizosaccharomyces pombe} genome}. Shown are the KR-normalized 5-kb resolution maps for all three \textit{S. pombe} chromosome (GEO accession GSM1379427).
\label{FigS32}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS30-Trypanosoma.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf No topological domains associated with gene arrays are observed in the kinetoplastid \textit{Trypanosoma brucei}}. Shown are KR-normalized 10-kb resolution maps for chr11 (A) and chr10 (B) for GEO accession GSM3346690.
\label{FigS30}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS15-Topo-PCNA-MCM-RPA-RFC1-V2.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Expansion of the Type II and II topoisomerase gene repertoire as well as of certain other replication-related proteins in dinoflagellates}. Shown are the number of genes annotated in MMETSP transcriptome assemblies of dinoflagellates and other eukaryotes. 
(A) Number of Type I topoisomerase genes;
(B) Number of Type II topoisomerase genes;
(C) Number of Type III topoisomerase genes;
(D) Number of PCNA genes;
(E) Number of MCM genes;
(F) Number of RPA1 genes;
(G) Number of RPA2 genes;
(H) Number of RPA3 genes;
(I) Number of RFC1 genes.
}
\label{FigS15}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS16-34C-scaffold10-V2.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Moderate decompaction of dinoTADs upon exposure to elevated temperatures}. Shown is pseudochromosome 10 (KR-normalized) and the difference between the KR-normalized Hi-C maps generated from \textit{B. minutum} grown at 34$\,^{\circ}\mathrm{C}$ and at 27$\,^{\circ}\mathrm{C}$ at 100-kb resolution (lower right) and 5-kb resolution (upper right).
\label{FigS16}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS17-34C-scaffold17-V2.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Moderate decompaction of dinoTADs upon exposure to elevated temperatures}. Shown is pseudochromosome 17 (KR-normalized) and the difference between the KR-normalized Hi-C maps generated from \textit{B. minutum} grown at 34$\,^{\circ}\mathrm{C}$ and at 27$\,^{\circ}\mathrm{C}$ at 100-kb resolution (lower right) and 5-kb resolution (upper right).
\label{FigS17}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS18-34C-scaffold18-V2.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Moderate decompaction of dinoTADs upon exposure to elevated temperatures}. Shown is pseudochromosome 18 (KR-normalized) and the difference between the KR-normalized Hi-C maps generated from \textit{B. minutum} grown at 34$\,^{\circ}\mathrm{C}$ and at 27$\,^{\circ}\mathrm{C}$ at 100-kb resolution (lower right) and 5-kb resolution (upper right).
\label{FigS18}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS33-amanitin-scaffold10.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Decompaction of dinoTADs upon transcriptional inhibition using $\alpha$-amanitin}. Shown is pseudochromosome 10. Two time courses were carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS33}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS34-amanitin-scaffold17.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Decompaction of dinoTADs upon transcriptional inhibition using $\alpha$-amanitin}. Shown is pseudochromosome 17. Two time courses were carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS34}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS35-amanitin-scaffold18.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Decompaction of dinoTADs upon transcriptional inhibition using $\alpha$-amanitin}. Shown is pseudochromosome 18. Two time courses were carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS35}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS40-metaplots-amanitin.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Decompaction of dinoTADs upon transcriptional inhibition using $\alpha$-amanitin}. Shown are 50-kb resolution metaplots centered on dinoTAD domain boundaries. Two time courses were carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS40}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS36-triptolide-scaffold10.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Blurring of dinoTAD boundaries upon transcriptional inhibition using triptolide}. Shown is pseudochromosome 10. The triptolide time course was carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS36}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS37-triptolide-scaffold17.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Blurring of dinoTAD boundaries upon transcriptional inhibition using triptolide}. Shown is pseudochromosome 17. The triptolide time course was carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS37}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS38-triptolide-scaffold18.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Blurring of dinoTAD boundaries upon transcriptional inhibition using triptolide}. Shown is pseudochromosome 18. The triptolide time course was carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS38}
}
\end{figure*}

\clearpage

\begin{figure*}[!ht]
\begin{center}
\includegraphics[width=18.5cm]{FigS39-metaplots-triptolide.png}
\end{center}
\captionsetup{singlelinecheck=off,justification=justified}
\caption{
{\bf Blurring of dinoTAD boundaries upon transcriptional inhibition using triptolide}. Shown are 50-kb resolution metaplots centered on dinoTAD domain boundaries. The triptolide time course was carried out following the outline presented in Figure \ref{Fig2}B.
\label{FigS39}
}
\end{figure*}

\clearpage

% \begin{figure*}[!ht]
% \begin{center}
% \includegraphics[width=10cm]{FigS28-FvFm-V2.png}
% \end{center}
% \captionsetup{singlelinecheck=off,justification=justified}
% \caption{
% {\bf \hl{XXX LEGEND Fv/FM}}. \hl{LEGEND GOES HERE}.
% \label{FigS28}
% }
% \end{figure*}

% \clearpage

\end{document}
