INS IG HT S | P E R S P E C T I V E S

that have low or no activity in the correspond- efforts to map the functional genome. The EVOLUTION
ing normal tissues, leading to activation of Roadmap Epigenomics (10) and Genotype-
large sets of gene regulatory elements (9). In
addition, many driver mutations affect chro-
matin modifiers or alter levels of CpG meth-
Tissue Expression (GTEx) (11) projects pri-
marily focus on normal tissues, whereas
the main drive of ENCODE (5) is to iden-
Our shallow-
ylation of DNA, leading to destabilization of
the entire chromatin regulatory system (1,
tify functional genomic elements; although
cancer cells are used as models in some of water origins
2). It is difficult for evolutionary processes to these projects, the cell lines used do not ad-
remove large sets of potentially harmful ele- equately represent major forms of human
Coastal habitats represent
ments from our genome, as each individual cancer. Previous epigenomic studies of can- a cradle of diversification
element has limited impact at the population cer, in turn, have mainly focused on targeted
level, and cancer generally affects individuals DNA methylation analysis (12), transcription
for early vertebrates
who are above reproductive age. Therefore, it factor binding analyses in a few cell lines
is likely that elements that are specifically ac- (13), or analysis of histone modifications in By Catalina Pimiento1,2
tivated in cancer are present in our genome. a particular type of cancer (14). In this con-

V
Identification of such elements will facilitate text, the study by Corces et al. is particularly ertebrates encompass all animals
improved diagnosis and prognosis, and also welcome because it paves the way toward a with a backbone, from fish to hu-
allow investigations of new therapeutic mo- large-scale effort to map the functional ge- mans. How and when they evolved
dalities to target oncogenic gene regulation. nome of cancer cells. To understand how in- are questions that have been studied
The mapping of accessible chromatin dividual tumors form, it is necessary to map for centuries, revealing the origins
landscapes is also important for the mech- their genomic features such as germline var- and processes involved in anatomical

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anistic understanding of tumorigenesis. It is iants, somatic mutations, chromosomal con- innovations such as jaws, teeth, and paired
known that altered activities of transcription tent, and allelic imbalance (15), together with appendages (1). A less explored, but equally
factors and/or their binding regions drive functional genomic features such as genes important question is where they evolved.
the major forms of human cancer. Cancer that are essential for growth and survival, On page 460 of this issue, Sallan et al. (2)
can thus be considered a disease of gene ex- three-dimensional (3D) chromosome con- compile a new database of early occur-
pression, where a combination of mutations formation, the DNA methylome, chromatin rences (mid-Paleozoic, 490 to 360 million
locks the gene regulatory network of a sin- modification state, and accessible chromatin years ago) and site-specific environmental
gle cell into a state that drives unrestricted landscape (see the figure). Comparing cancer information to reconstruct vertebrate an-
cell proliferation (6). Although mutations types to each other can yield interesting re- cestral habitats. They report that all major
in some oncogenes and tumor-suppressor sults but suffers from the disadvantage that vertebrate clades originated in restricted,
genes are commonly found across many all cancers share key phenotypic character- shallow-water environments.
forms of cancer, most driver genes are mu- istics, such as unrestricted growth. A better The environmental context of vertebrate
tated in a more restricted set of tumors. comparison would be between cancers and evolution had remained a gap in our knowl-
Some of the differences in oncogene com- their cell types of origin. However, the cell edge. Understanding the habitat constraints
position can be explained by differences in type of origin of many cancers is unknown,
mutational mechanisms and proto-oncogene and many tumors are thought to originate
expression between the cell types of origin of from relatively rare cells (for example, stem
the tumors. However, many oncogenes can- or progenitor cells). Therefore, it will also “What was so special
not transform fibroblastic cells in standard be necessary to develop analytical methods about the shallow-water
cell-based assays, suggesting that cell line- that can detect genomic features from minor
age–determining transcription factors col- cell populations or from single cells. Without habitats where
laborate in some way with oncogenes. The
mechanisms of such collaboration are cur-
such multiomic maps at the cell-type level,
it will be exceedingly difficult to move from
vertebrates diversified?”
rently poorly understood, but given that lin- genomics toward understanding the main
eage-determining factors commonly define drivers of the phenotype of individual tum- present when key traits evolved is neces-
chromatin states, it is likely that accessibil- ors. Without such understanding, we may sary to answering fundamental questions
ity of chromatin at specific regulatory sites not be able to conquer cancer. j in macroevolution such as the extent to
contributes to this process. An important which the environment can drive anatomi-
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1
Department of Biosciences, Swansea University, Swansea,
Traditionally, there has been a disconnect UK. 2Smithsonian Tropical Research Institute, Panama.
between cancer genomics and large-scale 10.1126/science.aav3494 Email: cpimiento@swansea.ac.uk

402 26 OCTOBER 2018 • VOL 362 ISSUE 6413 sciencemag.org SCIENCE

Published by AAAS
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Nevertheless, early fish managed to occupy
different aquatic environments along the
depth gradient. Interestingly, dispersal into Nearshore environments are the cradle of vertebrate evolution
habitats outside the cradle were not neces- Shallow subtidal environments represent the ancestral habitats of early fish.
sary to evolve new phenotypes. Instead, ma-
jor body forms [benthic (those adapted to
live on the bottom of the ocean) and pelagic Upland Supratidal Intertidal Subtidal
(those adapted to live in the water column)]
originated in shallow waters before expand-
ing to new habitats.
What was so special about the shal-
low-water habitats where vertebrates di-
versified? The mid-Paleozoic nearshore
environments were somewhat different
from those of today. Seagrasses, mangroves, The subtidal region
Subtidal habitats support fish diversity by offering habitat heterogeneity,
and modern coral reefs had yet to appear. physical structure, trophic complexity, and shelter.
Nevertheless, habitat-forming species such
as stromatolites, sponges, and early corals
were present (5). During this time, these
habitats experienced fundamental evolu-
tionary changes as the water column gradu-
ally filled with newly evolved nektonic
forms (organisms able to freely swim) (7).
Exploitation of the vertical habitat dimen-
sion was likely driven by competition in the
saturated benthic zone, and by increased
ocean productivity resulting from riverine Starfish Mussels
influx when arborescent flora evolved on Sea
land (8). Although these transformations Kelp urchins
took place in all coastal habitats, most origi-
nation occurred in lagoon-like systems, and
therefore in sheltered areas. Was the com-
bination of heterogeneity, habitat structure,
and protection the foundation for the diver-
Fish
sification of major vertebrate clades?
Today, protected shallow-water ecosys-
GRAPHIC: A. KITTERMAN/SCIENCE

tems are not only biodiversity hotspots,

but also serve as essential nurseries for fish
(e.g., coral reefs, estuaries, and mangroves).
These ecosystems offer physical structure, Fan
habitat heterogeneity, and trophic complex- Sea coral
grass Sponges
ity, thus providing abundant food and ref-
uge to marine fauna, as well as important Brain coral

SCIENCE sciencemag.org 26 OCTOBER 2018 • VOL 362 ISSUE 6413 403

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Our shallow-water origins
Catalina Pimiento

Science 362 (6413), 402-403.

DOI: 10.1126/science.aau8461

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