Simple Animals, Complex Genomes
Comparative genomics of sponges, sea
anemones, and multicellular pancakes
Mansi Srivastava
Rokhsar 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
What is the genomic basis for the difference in complexity?
BILATERIANS
PLACOZOAN
S
SPONGES
CNIDARIANS
bilateral symmetry,
centralized nervous
system
true muscle
true gut
nervous system
tissue grade
?
multicellularity
Three species were selected for genome
sequencing
SEA ANEMONE
PLACOZOAN
SPONGE
Nematostella vectensis is a sea anemone
Nematostella is a great lab rat
(Finnerty et al. 2004)
Trichoplax is a placozoan
(photo credits: Ana Signorovitch, Michael Eitel, Bernd Schierwater)
Amphimedon queenslandica is a sponge
Adult
Larvae
(photo credits: Bernie Degnan)
These animal genomes have been sequenced
using a Whole Genome Shotgun strategy
ATTTGCATGCGTAATTCAAT
CGTAATTCAATGTGTGATTC
ATTTGCATGCGTAATTCAAT
CGTAATTCAATGTGTGATTC
ATTTGCATGCGTAATTCAATGTGTGATTC
These animal genomes have different sizes, but the
numbers of genes/proteins are in the same ballpark
Genome
exon
intron
Genes
Proteins
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
Before comparing their genomes, we need to know how
these animals are related to each other and to us
*
*
*
BILATERIANS
Not an ancient animal gene
*
*
*
BILATERIANS
Ancient animal gene
Lost in sponges
Orthologous protein sequences can reveal how
organisms are related to each other
RLKMTPIR PIDWDCMW MTLPDCMW
fly
fish
RKLPDCMW
human
mouse
Live birth, hair, warm blood, four
chambered heart
vertebrae
RLKMTPIR PIDWDCMW MTLPDCMW
RKLPDCMW
Placozoans represent a sister lineage
to cnidarians and bilaterians
Cnidaria
Bilateria
Animals
Whole-genome data can resolve early animal
relationships
BILATERIANS
SPONGES
PLACOZOAN
S
CNIDARIANS
bilateral symmetry,
centralized nervous
system
true muscle
true gut
nervous system
tissue grade
multicellularity
Previously, some developmental processes were
thought to be conserved in the bilaterian ancestor
A-P patterning
Hox 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
exon
Genes
Proteins
intron
Sea anemones, placozoans, and sponges have
preserved
many (>80%) ancient introns
(this is not the case for flies and nematodes, which have lost
a majority of ancestral metazoan introns)
(in collaboration with Uffe Hellsten)
What about how genes are organized relative to each
other?
The positions of orthologous genes can be compared
between two species
“dot plot view”
Fly
Insect
abd-B
lab
pb
dfd
scr antp
ubx abd-A
abd-B
abd-A
Ubx
Antp
hox6
hox8
hox1 hox2 hox3 hox4hox5
hox7
Scr
Dfd
pb
lab
Mammal
hox 1
2
3
4
5
6
Mouse
7
8
9
10
11
Human Chr 1
Gene order conservation decreases
with evolutionary distance
1
3
Mouse
4
3
8
21
Chicken
23
VIII
X
Stickleback
Synteny “same thread”
genes present on the same chromosome
Human
No chromosome scale synteny is observed between
vertebrates and flies
Drosophila
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.
2.
3.
4.
5.
6.
Regulated cell cycle and growth
Programmed cell death
Cell-cell and cell-matrix adhesion
Allorecognition and innate immunity
Specialization of cell types
Developmental signaling
Comparing early animal genomes allows us to study the
temporal origins of animal biology
Six hallmarks of animal multicellularit
1.
2.
3.
4.
5.
6.
Regulated cell cycle and growth
Programmed cell death
Cell-cell and cell-matrix adhesion
Developmental signaling
Allorecognition and innate immunity
Specialization of cell types
Some essential controls on the cell cycle evolved
when animals first appeared
A-P patterning,
Hox complex
Early animal genomes are (in some ways) more similar to our
genome than are the genomes of flies and nematodes
SPONGES
PLACOZOAN
S
CNIDARIANS
BILATERIANS
A-P patterning
Hox complex
Metazoan “toolkit”
Most signaling pathway and transcription
factor families, intron-exon structure,
genome organization
Explanations for differences in complexity
SPONGES
PLACOZOAN
S
CNIDARIANS
BILATERIANS
microRNAs?
cis-regulation?
larger families?
A-P patterning
Hox complex
Most signaling pathway and transcription
factor families, intron-exon structure,
genome organization
Differences in the numbers of some types of genes do
correlate with complexity
Explanations for differences in complexity
SPONGES
PLACOZOAN
S
CNIDARIANS
BILATERIANS
microRNAs?
cis-regulation?
larger families?
A-P patterning
Hox complex
Cell types patterned in
complex ways?
Most signaling pathway and transcription
factor families, intron-exon structure,
genome organization
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 Rokhsar
Nik Putnam, Oleg Simakov
Jarrod Chapman, Emina Begovic
Therese 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 Mazza
Members of the Reddien Lab
Ulf Jondelius, Swedish Museum of Natural History
Wolfgang Sterrer, Bermuda Natural History Museum