Download The Role of Gene Loss in Animal Evolution Edward M. De Robertis

Evolving Concepts: The Role of Gene Loss in Animal
Evolution
Edward M. De Robertis
HHMI/UCLA, USA
Animal evolution used an ancestral “genome tool-kit” shared by all
bilateral animals.
1) Whole-genome duplications followed by massive gene loss were
very important evolutionary events.
2) Gene deletions are common, but limit future evolutionary
change.
3) Similar functions can be fulfilled by very different genes – the
case of self-avoidance in neurons.
Slide 1
Genomes contain the record of our evolutionary history
Ur = Primeval
Bilateria = all bilateral animals (30 phyla)
Slide 2
The common ancestor Urbilateria used conserved systems of
developmental control genes.
BMP
Hox
Chd
De Robertis & Sasai, Nature 1996
Slide 3
The Chordin/BMP network patterns D-V differentiation in
vertebrates, Drosophila, and many other animals.
De Robertis, Cell 2008
Slide 4
Fish, amphibians, reptiles and birds have a
conserved Dorsal-Ventral regulatory system
Platypus
Higher Mammals
Slide 5
Edward B. Lewis
Walter J. Gehring
Homeotic genes specify A-P segment identity in Drosophila.
Colinearity between their order in DNA and in the body.
Slide 6
Homeobox DNA encodes a DNA-binding protein
domain of 60 amino acids called the Homeodomain.
“A Xenopus laevis gene was cloned on the basis of
cross-homology to a region conserved between
several Drosophila homeotic genes… This gene
could perhaps represent the first developmentcontrolling gene identified in vertebrates.”
Carrasco, McGinnis, Gehring and De Robertis, Cell
1984
Slide 7
Hox gene complexes
P. Holland, WIREs Dev. Biol. 2, 31-45 (2013)
Slide 8
Whole-genome duplications
Ecdysozoa
Deuterostomes
Urbilateria
P. Holland, WIREs Dev. Biol. 2, 31-45 (2013)
Slide 9
Susumu Ohno published the prescient book “Evolution by
Gene Duplication” in 1970.
Using cytogenetics and DNA quantification methods he
predicted that two whole-genome duplication events had
occurred during vertebrate evolution.
He also predicted that bony fishes would be 8X, and that the
surf smelt (8X), trout (16X) and salmon (32X) were a
polyploid series.
He realized that duplications gave the opportunity for two
genes to adopt different function or regulation.
The role of gene deletion is less generally recognized.
Slide 10
Tandem duplications in DNA occur readily by unequal crossing over
For each duplication there is an accompanying deletion.
Slide 11
Comparison of the amphioxus genome to the human genome showed
that 25% of human genes retained 2 or more copies. Thus, a process of
massive gene loss left humans with 75% of our protein-coding genes as
single copy.
Nature 453, 1064-1071 (2008)
Slide 12
Homeobox transcription factor loss in chordates.
Ascidians lost
2,250 gene
families present
both in amphioxus
and humans
Chordate
ancestor
560 Mya
Holland et al. Genome Res. 18, 1100-1111 (2008)
Slide 13
Baker’s yeast (Saccharomyces cerevisiae) underwent an ancient
whole-genome duplication followed by massive gene deletions
of 88% of the duplicated genes. The 12% that remained
duplicated have diverged in sequence and function.
Slide 14
Loss-of-function represents a common response to changes in the
environment or in habits
In vampire bats a change in feeding habit led to a very
thin esophagus and can no longer feed on insects.
Laboratory mice reproduce throughout the year, instead of
seasonally. Caused by mutations in two enzymes that
synthesize melatonin from serotonin in the pineal gland.
kiwi
Flightless birds and beetles. Darwin described that in the
windy island of Madeira of 550 beetle species 200 have
become flightless.
Slide 15
Sticklebacks are marine fish that spawn in fresh water. They became
trapped in lakes 10,000 years ago after the last ice age. They represent
very recent, and repeated, natural evolutionary experiments.
Slide 16
Sticklebacks have lost the pelvic spines independently in diverse populations
Why would sticklebacks ever lose the pelvis?
• Shallow lakes often contain insect predators that grasp spines
(After Reimchen, 1980)
Slide 17
Pelvic spine loss occurred by multiple independent deletions of an
enhancer DNA region required for Pitx1 gene expression in the pelvis.
(Work of David Kingsley.)
Ectodysplasin mutations cause loss of armored plates but this
mutation was present in the marine population.
Slide 18
Urbilateria: a complex or simple animal?
Slide 19
The notochord is a flexible rod used for swimming in the chordates
Slide 20
Slide 21
The notochord of the chordate amphioxus is also muscular but the contractile
nature was lost when the vertebrate notochord became a flexible rod.
Detlev Arendt et al., Science 2014
Slide 22
Generating diversity: “Nature is very inventive”.
Self- avoidance in neuronal circuits is mediated by Dscam in
Drosophila and by protocadherins in mammals.
Slide 23
Self-avoidance is essential for neurons to form the proper circuits. Mutation of
Dscam1 (Down syndrome cell adhesion molecule) gene in Drosophila
eliminates repulsion between branches of the same neuron.
Larry Zipursky
Slide 24
Drosophila uses alternative splicing of mRNA to generate many Dscam proteins.
12 x 48 x 33 x 2 = 38,016 different proteins from one gene. Fruit flies have 15,000
genes and humans about 20,000 protein-coding genes.
Only when the three variable Ig domains match each other the extracellular
domains recognize each other and they stimulate repulsion via the cytoskeleton.
Each neuron is unique because it expresses 10-20 Dscam1s stochastically
Zipursky and Sanes, Cell 143, 343-353 (2010)
Slide 25
In mice and men clustered protocadherin genes use alternative promoters to
express the proteins stochastically in neurons. Homophilic binding of tetrameric
proteins triggers repulsion and self-avoidance but using a completely different
transmembrane protein.
Tom Maniatis et al., Nature 2012
Slide 26
Monod proposed a new “ethics of
knowledge” with the main guiding
principle being the principle of objectivity.
In the end it was a dark message:
“The ancient covenant is in pieces; man
knows at last that he is alone in the
universe’s unfeeling immensity, out of
which he emerged only by chance.”
Chance and Necessity, p. 180, 1972.
F. Jacob took a more optimistic view:
“Western science is founded on the
monastic doctrine of an orderly universe
founded by God who stands outside of
nature and controls it through laws
"Onlyaccessible
if the Redeemer
is also
Creator can he
to human
reason”.
really The
be Redeemer.
That
why the
Possible and
theisActual,
p. question
10, 1982.
of what we do is decided by the ground of
what we
are. Weresponse
can win came
the future
A stronger
fromonly
the if we
do notFrauenkirche
lose creation."
in Munich:
Slide 27
"Only if the Redeemer is also Creator can he
really be Redeemer. That is why the question
of what we do is decided by the ground of
what we are. We can win the future only if we
do not lose creation."
Similar views are held by Pope Francis: In fact, the Pope explained, “God made
things — each one — and he let them go with the interior, inward laws which he
gave to each one, so that they would develop, so they would reach fullness.”
Slide 28
In sum, animals evolved through variations in
ancestral developmental gene networks in our DNA.
It seems a miracle that we humans got to where we
are today through evolutionary gains and losses of
an ancient set of animal genes.
Slide 29
Conclusions:
Animals derive from a conserved animal genomic tool-kit.
1) Developmental control networks placed evolutionary
constraints on the animal anatomies that evolved by natural
selection. The results of evolution are dependent on constraints
imposed by our previous history.
2) Genome-wide duplications followed by copious deletions
facilitated adaptations in the course of evolution.
3) Genes that are no longer needed are rapidly deleted but this
causes loss of potential to evolve.
4) Very different genes can be used to achieve the same
physiological needs.
Slide 30