Simple Animals, Complex Genomes

Comparative genomics of sponges, sea anemones, and multicellular pancakes

Mansi SrivastavaRokhsar Lab, Department of Molecular and Cell Biology, UC Berkeley

Reddien Lab, Whitehead Institute for Biomedical Research

02.23.13

Outline

1. Introduction

2. Insights from genomic analyses

3. Linking genomic complexity to biological complexity

CNIDARIANSPLACOZOANS SPONGES

What is the genomic basis for the difference in complexity?

BILATERIANS

?

bilateral symmetry, centralized nervous systemtrue muscle

true gutnervous systemtissue grade

multicellularity

Three species were selected for genome sequencing

SEA ANEMONE SPONGEPLACOZOAN

Nematostella vectensis is a sea anemone

(Finnerty et al. 2004)Nematostella is a great lab rat

Trichoplax is a placozoan

(photo credits: Ana Signorovitch, Michael Eitel, Bernd Schierwater)

Amphimedon queenslandica is a spongeAdult

Larvae

(photo credits: Bernie Degnan)

ATTTGCATGCGTAATTCAAT

CGTAATTCAATGTGTGATTC

ATTTGCATGCGTAATTCAAT

CGTAATTCAATGTGTGATTC

ATTTGCATGCGTAATTCAATGTGTGATTC

These animal genomes have been sequenced using a Whole Genome Shotgun strategy

Nematostella(cnidarian)

Trichoplax(placozoan)

Amphimedon(sponge) Human C. elegans

(nematode)Drosophila(fruit fly)

Genome size (Mb) 450 98 190 3,000 97 120

Gene Models ~18,000 ~11,500 ~24,000 ~20,000 ~20,000 ~14,000

Genome

Genes

Proteins

These animal genomes have different sizes, but the numbers of genes/proteins are in the

same ballpark

exon intron

Before comparing their genomes, we need to know how these animals are related to each other

and to us

BILATERIANS BILATERIANS

* * * *

Not an ancient animal gene

Ancient animal gene Lost in sponges

* *

Orthologous protein sequences can reveal how organisms are related to each other

mouse humanfishfly

Live birth, hair, warm blood, four chambered heart

vertebrae

MTLPDCMW RKLPDCMWPIDWDCMWRLKMTPIR

MTLPDCMW RKLPDCMWPIDWDCMWRLKMTPIR

Placozoans represent a sister lineage to cnidarians and bilaterians

Bilateria

Cnidaria

Animals

CNIDARIANSPLACOZOANSSPONGES

Whole-genome data can resolve early animal relationships BILATERIANS

multicellularity

bilateral symmetry, centralized nervous systemtrue muscle

true gutnervous systemtissue grade

Previously, some developmental processes were thought to be conserved in the bilaterian

ancestor

A-P patterningHox complex

Gene structure or genome organization (except for the Hox cluster) were not known to be ancient

How do the structures of genes compare between animal genomes?

Genome

Genes

Proteins

exon intron

Sea anemones, placozoans, and sponges have preserved

many (>80%) ancient introns

(in collaboration with Uffe Hellsten)

(this is not the case for flies and nematodes, which have lost a majority of ancestral metazoan introns)

What about how genes are organized relative to each other?

The positions of orthologous genes can be compared between two species

Gene order conservation decreases with evolutionary distance

Synteny “same thread”genes present on the same chromosome

No chromosome scale synteny is observed between vertebrates and flies

Drosophila

Hum

an

Nematostella, Trichoplax, and Amphimedon scaffolds show conserved synteny with human chromosome

segments

(Nik Putnam)

There is considerable scrambling of gene order in these blocks of conserved synteny

(Nik Putnam)

What is the significance of this conserved synteny?

Another way to compare genomes is in terms of gene content…

Trichoplax has genes for neurons and epithelial cells

Trichoplax has genes for developmental signaling pathways

Early animal lineages may lack certain cell types or biological processes, but their genomes encode the

proteins required for these in bilaterians

Many “important” genes are involved in processes essential for animal multicellularity

Six hallmarks of animal multicellularity:

1. Regulated cell cycle and growth2. Programmed cell death3. Cell-cell and cell-matrix adhesion4. Allorecognition and innate

immunity5. Specialization of cell types6. Developmental signaling

Comparing early animal genomes allows us to study the temporal origins of animal biology

Six hallmarks of animal multicellularity:

1. Regulated cell cycle and growth2. Programmed cell death3. Cell-cell and cell-matrix adhesion4. Developmental signaling5. Allorecognition and innate

immunity6. Specialization of cell types

Some essential controls on the cell cycle evolved when animals first appeared

A-P patterning, Hox complex

A-P patterning Hox complex

Most signaling pathway and transcription factor families, intron-exon structure, genome organization

Early animal genomes are (in some ways) more similar to our genome than are the genomes of flies and nematodes

CNIDARIANSPLACOZOANSSPONGES BILATERIANS

Metazoan “toolkit”

A-P patterning Hox complex

Most signaling pathway and transcription factor families, intron-exon structure, genome organization

CNIDARIANSPLACOZOANSSPONGES BILATERIANS

Explanations for differences in complexity

microRNAs? cis-regulation?larger families?

Differences in the numbers of some types of genes do correlate with complexity

A-P patterning Hox complex

Most signaling pathway and transcription factor families, intron-exon structure, genome organization

CNIDARIANSPLACOZOANSSPONGES BILATERIANS

Cell types patterned in complex ways?

microRNAs? cis-regulation?larger families?

Explanations for differences in complexity

Summary

Animals evolved a “toolkit” of genes very early in their evolution

Early animal genomes are complex!(as are these animals)

Though not all questions are answered by the genomes, they are essential tools for finding the

remaining answers

Acknowledgements

Dan RokhsarNik Putnam, Oleg SimakovJarrod Chapman, Emina BegovicTherese Mitros, Uffe Hellsten

Heather Marlow and Mark Martindale (U. Hawaii)Kai Kamm, Michael Eitel, Bernd Schierwater (Hanover)Ana Signorovitch, Maria Moreno, Leo Buss, Stephen Dellaporta (Yale)Degnan group (U. Queensland), Kosik group (UC Santa Barbara)

Peter Reddien

Jessica Witchley, Kathleen MazzaMembers of the Reddien Lab

Ulf Jondelius, Swedish Museum of Natural HistoryWolfgang Sterrer, Bermuda Natural History Museum