Genomic EvoDevo Lab

How did Multicellularity Evolve?



Evolution of animal (metazoan) multicellularity should have required a lot of molecular-level innovations such as cell adhesion molecules, cell-to-cell communication tools, and cell differentiation machinery. Where did the genes encoding these mechanisms come from? Recent studies of comparative genomics have revealed that surprisingly many "multicellularity" genes were already present in the unicellular ancestor of metazoans. It is therefore considered that the animal's ancestor reused these "old" genes for new functions to develop multicellularity. However, the nature of this "co-option" process is totally unknown. For instance, what were the ancestral functions of these genes? Why did unicellular organisms need the multicellularity genes?

The "cell" of Capsaspora, a unicellular relative of metazoans (Suga & al. 2013 Nat. Comm.). Coloured genes are already present in Capsaspora. Blue genes are secondary lost (but present in Capsaspora) in the choanoflagellate Monosiga brevicollis.

To know the function of "multicellularity" genes abundantly found in the unicellular relatives of metazoans, we use new model organisms: ichthyosporeans and filastereans.

Ichthyosporeans are mostly symbionts of marine animals. Some are fish parasites, damaging the fishery industry. They had long been considered to be fungi, but later turned out to be close relatives of metazoans. The life cycle of many ichthyosporeans starts from a single cell, which simply grows in size. In the growth stage the nuclear divides without cytoplasmic division, thus producing a "syncytium". After the growth stage, the syncytium cellularises and the produced daughter cells scatter (video). The daughter cells of some ichthyosporeans can migrate efficiently by amoeboid movement. Interestingly, some ichthyosporeans produce a characteristic colony, which morphologically resembles the animal blastula.

Life cycle of the ichthyosporean Creolimax fragrantissima (Suga & al. 2013 Dev. Biol.)

We have recently developed the technique for transforming Creolimax cells by electroporation (video). Gene silencing by siRNA and Morpholino is also possible by the use of this technique.

Small interference RNA surpresses gene expression in Creolimax cell (Suga & al. 2013 Dev. Biol.)

Filastereans include only two known genera: Capsaspora and Ministeria. Capsaspora owczarzaki (video), the only Capsaspora species described to date, is a symbiont to the snail Biomphalaria. Biomphalaria is known as an intermediate host for Schistosoma mansoni, which causes the second most devastating parasitic disease (after WHO). Capsaspora is considered to prey on Schistosoma sporocyst within the host snail. Phylogenetically, Capsaspora is the second closest unicellular relative to metazoans in our current knowledge. Thus Capsaspora is also a promising model for deciphering the enigmatic origin of multicellularity, and possibly offers a solution to schistosomiasis.

Capsaspora cells (photo by Lora Lindley; Suga & al. 2013 Nat. Comm.)

We are also working on the fancy dinoflagellates with a big "eye". This project started on 2003, when the PI Suga was a post-doc in Prof. Gehring lab in Basel, with a collaboration of Prof. Gojobori's lab in Nationa Institute of Genetics in Japan. These unicellular protists have an ocellus, which is nicely equipped with a huge shiny lens, a red-black pigment, and a retina-like stacking structure.

The dinoflagellate Nematodinium caught at the Inland Sea of Japan in 2015, by a help of Dr. Setsuko Sakamoto.

Capsaspora owczarzaki genome sequence version4

Available here . Please cite the published paper.
The modified scaffold 22 of the Oyster genome is available here.

Publication (since 2006)

Revision of the Capsaspora genome using read mating information adjusts the view on premetazoan genome
Denbo S, Aono K, Kai T, Yagasaki R, Ruiz-Trillo I, and Suga H
Development Growth and Differentiation 2019, 61, p34-42

Transglutaminase-mediated cross-linking of WDR54 regulates EGF receptor-signaling
Maeda A, Nishino T, Matsunaga R, Yokoyama A, Suga H, Yagi T, Konishi H
BBA - Molecular Cell Research 2018, 1866, 2, p285-295

Unicellular origin of the animal microRNA machinery
Bråte, J., Neumann, R. S., Fromm, B., Haraldsen, A. A. B., Tarver, J. E., Suga, H., Donoghue, P. C. J., Peterson, K. J., Ruiz-Trillo, I., Grini, P. E. and Shalchian-Tabrizi, K.
Current Biology 2018, 28, p3288-3295

Transfection of Capsaspora owczarzaki, a close unicellular relative of animals
Parra-Acero, H, Ros-Rocher, N., Perez-Posada, A., Kożyczkowska, A., Sánchez-Pons, N., Nakata, A., Suga, H., Najle, S. R., Ruiz-Trillo, I.
Development 2018 : dev.162107 doi: 10.1242/dev.162107

Src signaling in a low-complexity unicellular kinome
Suga, H. and Miller, T.
Sci Rep 2018, 8:5362

Historical geography of urushi, a Japanese traditional lacquer, in the Miyoshi area, Hiroshima
Takeda, K. and Suga, H.
J Life Environ Sci (生命環境学術誌)2018, 10:13-23

Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis
Gentekaki, E., Curtis, B. A., Stairs, C., Klimeš, V., Eliáš, M., Salas, D., Herman, E. K., Eme, L., Arias, M. C., Henrissat, B., Hilliou, F., Klute, M. J., Suga, H., Malik, S.-B., Pightling, A. W., Kolisko, M., Rachubinski, R. A., Schlacht, A., Soanes, D. M., Tsaousis, A. D., Archibald, J. M., Ball, S. G., Dacks, J. B., Clark, C. G., van der Giezen, M., Roger, A. J.
PLoS Biology 2017, 15 e2003769

Dynamics of genomic innovation in the unicellular ancestry of animals
Grau-Bové, X., Torruella, G., Donachie, S., Suga, H., Leonard, G., Richards, T. A., Ruiz-Trillo, I
eLife 2017 6 e26036

Radiation-induced RhoGDIβ cleavage leads to perturbation of cell polarity: a possible link to cancer spreading
Fujiwara, M., Okamoto, M., Hori, M., Suga, H., Jikihara, H., Sugihara, Y., Shimamoto, F., Mori, T., Nakaoji, K., Hamada, K., Ota, T., Wiedemuth, R., Temme, A., and Tatsuka, M.
J Cell Physiol 2016 231 2493-2505

Possibility of RhoGDIβ as a molecular target for biomedical applications (in Japanese)
Tatsuka, M., Fujiwara, M., Okamoto, M., Hori, M., Sugihara, Y., Jikihara, H., Nakaoji, K., Hamada, K., Suga, H., and Shimamoto, F.
J Life Environ Sci 2016 8 1-12

Complex transcriptional regulation and independent evolution of fungal-like traits in a relative of animals
De Mendoza A, Suga H, Permanyer J, Irimia M, Ruiz-Trillo I
eLife Oct 2015 (Cite as 2015;10.7554/eLife.08904)

The article is reviewd by Nature Research Highlights.Nature

Function and Evolutionary Origin of Unicellular Camera-Type Eye Structure
Hayakawa S, Takaku Y, Hwang JS, Horiguchi T, Suga H, Gehring WJ, Ikeo K and Gojobori T
PLoS ONE  10 e0118415   Mar 2015

Filastereans and Ichthyosporeans: Models to Understand the Origin of Metazoan Multicellularity
Suga H and Ruiz-Trillo I
A chapter in the book Evolutionary Transitions to Multicellular Life (Springer) Apr 2015 (PDF available for non-commercial purposes - email me)

Unraveling the Origin of Multicellularity (in Japanese)
Suga H and Ruiz-Trillo I
Experimental Medicine (実験医学) 33 968-973 Apr 2015

The holozoan Capsaspora owczarzaki possesses a diverse complement of active transposable element families.
Carr M, Suga H
Genome biology and evolution   6 949-963   Apr 2014

Earliest holozoan expansion of phosphotyrosine signaling.
Suga H, Torruella G, Burger G, Brown MW, Ruiz-Trillo I
Molecular biology and evolution   31 517-528   Mar 2014

Regulation of Src and Csk nonreceptor tyrosine kinases in the filasterean Ministeria vibrans.
Schultheiss KP, Craddock BP, Suga H, Miller WT
Biochemistry   53 1320-1329   Mar 2014

Development of ichthyosporeans sheds light on the origin of metazoan multicellularity.
Suga H, Ruiz-Trillo I
Developmental biology   377 284-292   May 2013

Molecular phylogeny of unikonts: new insights into the position of apusomonads and ancyromonads and the internal relationships of opisthokonts.
Paps J, Medina-Chacón LA, Marshall W, Suga H, Ruiz-Trillo I
Protist   164 2-12   Jan 2013

The Capsaspora genome reveals a complex unicellular prehistory of animals.
Suga H, Chen Z, de Mendoza A, Sebé-Pedrós A, Brown MW, Kramer E, Carr M, Kerner P, Vervoort M, Sánchez-Pons N, Torruella G, Derelle R, Manning G, Lang BF, Russ C, Haas BJ, Roger AJ, Nusbaum C, Ruiz-Trillo I
Nature communications   4 2325   2013
Access the recommendation on F1000Prime

Lack of Csk-mediated negative regulation in a unicellular SRC kinase.
Schultheiss KP, Suga H, Ruiz-Trillo I, Miller WT
Biochemistry   51 8267-8277   Oct 2012

The "eyes absent" (eya) gene in the eye-bearing hydrozoan jellyfish Cladonema radiatum: conservation of the retinal determination network.
Graziussi DF, Suga H, Schmid V, Gehring WJ
Journal of experimental zoology. Part B, Molecular and developmental evolution   318 257-267   Jun 2012

Genomic survey of premetazoans shows deep conservation of cytoplasmic tyrosine kinases and multiple radiations of receptor tyrosine kinases.
Suga H, Dacre M, de Mendoza A, Shalchian-Tabrizi K, Manning G, Ruiz-Trillo I
Science signaling   5 ra35   May 2012
Science Podcast
(Journal cover)   (Digest version in Japanese)

Flexibly deployed Pax genes in eye development at the early evolution of animals demonstrated by studies on a hydrozoan jellyfish.
Suga H, Tschopp P, Graziussi DF, Stierwald M, Schmid V, Gehring WJ
Proceedings of the National Academy of Sciences of the United States of America   107 14263-14268   Aug 2010

Evolution of the MAGUK protein gene family in premetazoan lineages.
de Mendoza A, Suga H, Ruiz-Trillo I
BMC evolutionary biology   10 93   Apr 2010

The evolutionary history of lysine biosynthesis pathways within eukaryotes.
Torruella G, Suga H, Riutort M, Peretó J, Ruiz-Trillo I
Journal of molecular evolution   69 240-248   Sep 2009

Evolution of the Hox gene complex from an evolutionary ground state.
Gehring WJ, Kloter U, Suga H
Current topics in developmental biology   88 35-61   2009

Ancient divergence of animal protein tyrosine kinase genes demonstrated by a gene family tree including choanoflagellate genes.
Suga H, Sasaki G, Kuma K, Nishiyori H, Hirose N, Su ZH, Iwabe N, Miyata T
FEBS letters   582 815-818   Mar 2008

Evolution and functional diversity of jellyfish opsins.
Suga H, Schmid V, Gehring WJ
Current biology : CB   18 51-55   Jan 2008
(Basler Zeitung article)

Functional development of Src tyrosine kinases during evolution from a unicellular ancestor to multicellular animals.
Segawa Y, Suga H, Iwabe N, Oneyama C, Akagi T, Miyata T, Okada M
Proceedings of the National Academy of Sciences of the United States of America   103 12021-12026   Aug 2006