Petrellen-LiU3-20171024115924nonunfit Carlos
Guerrero-Bosagna
N.B.: When citing this work, cite the original publication.
Guerrero-Bosagna, C., (2017), Epigenetics, evolution and the
survival of the non-unfit, The Biochemist, 39(5), 8-11.
Original publication available at:
http://www.biochemistry.org/Publications/TheBiochemistmagazine.aspx
Copyright: Portland Press
http://www.portlandpresspublishing.com/
Epigenetics, evolution and the survival of the non-unfit Carlos
Guerrero-Bosagna
(Linki:iping University, Sweden)
-4,600 4,0CO 3,600
The transition that occurred in vertebrates moving from water to
land was a major step in the evolution of terrestrial animals. This
is an evolutionary step that has always fascinated scientists and
the general public. The land-to-water vertebrate transition
happened around the Devonian period and involved structural changes
such as the transition from fin to limb, a reduction of the gill
arch, loss of the mid-fin and a reduction in the number of scales,
among others. I will use this interesting example to depict how the
same evolutionary process can be seen through two
different lenses. One view, which is the most widespread way of
seeing evolution, is the 'survival of the fittest'. The other is
intentionally stated in the title as the double negative 'survival
of the non-unfit'. Only semantic differences? Not in my view.
Evolution through the lens of the 'survival of the fittest' can be
defined as benefit-driven evolution, and assumes that the majority
of the traits we observe in organisms exist because they confer, or
have conferred, advantage to some individuals over others.
Moreover, these advantageous traits are assumed to be fully encoded
within the genome, so that natural selection upon the phenotype
will also act upon the genome that generated that phenotype.
Now, let's see the water-to-land transition under the lens of the
'survival of the fittest': when the aquatic
tetrapods transitioned to land, adaptations were required
in order to live terrestrially, thus structural changes
originated in order to allow for movement and respiration
on land. This view, which could be quite familiar to any reader,
implies that the structural novelties only
originated because they conferred adaptation to a new environmental
reality.
Archean Proterozoic
Let's now see the water-to-land transition from the other
perspective. Let's imagine that the novel structures didn't
originate to produce adaptation. Let's imagine that they appeared
previously as a non-detrimental characteristic, which allowed some
individuals to explore outside the aquatic world and finally
establish themselves on land. This is the same evolutionary process
seen now through the lens of the 'survival of the non-unfit: or in
other words, neutral evolution. From this perspective, most of what
has survived in evolution has not necessarily conferred advantage
to individuals, it has simply survived due to not being
detrimental. Thus, the survivors would not only be the fittest, but
would also include those that did not have detrimental traits (e.g.
those that survived negative selection), in other words, those
non-unfit. How realistic is such a proposition? This we will see in
the next sections.
Paleozoic (Pat 1)
3,200 2.800 2500 1,600 l,CXX> 541 485 443
millions of years ago
The neutral theory of evolution
The neutral theory of molecular evolution was introduced by Motoo
Kimura, formally in 1968, after having described the concept of
genetic drift in previous years. In Kirnura's own words: "the
neutral theory claims
that the overwhelming majority of evolutionary changes at the
molecular level are caused by random fixation of selectively
neutral mutants under continued inputs of mutations" and "rejects
the notion that the majority of [DNA or protein] polymorphisms are
adaptive and actively maintained in the species by some form of
balancing selection". In other words, according to Kimura, most of
what has survived in evolution does not, and has not, conferred
fitness advantages to individuals.
But what about experimental biology? Is Kirnura's prediction
sustained by available data? In 2007, a study by Eyre-Walker and
Keightley quantified the influence of genomic variability on
fitness across species and concluded that advantageous mutations
are indeed rare. Estimates by Ponting and Lunter in 2006 indicate
that in addition to 2.5-5% of the human genome that would have
evolved by purifying selection, essentially all of the remaining
sequences would have evolved neutrally, with positive selection
(i.e. associated with adaptation and increased fitness) being rare.
Recent experimental evidence indicates a similar trend. A 2014
study of the radiation of African cichlid fish concluded that
neutral evolution was key in producing the genetic variability
related to the variety of phenotypes observed. Adaptive processes,
in turn, would only have helped in partially sorting this
variation.
Another example of interest relates to whole genome amplification
events leading to the formation of new bacteria or organelles. The
evolution of mutation rates, genome size and chromosome structure
in these scenarios has been shown to be remarkably fast, and
Paleozoic (Part 2)
358 298 252
Epigenetics
with unexpected degrees of interdependency. Non adaptive processes
have been shown to be behind the expansion of non-coding regions in
organelle genomes, as well as involved in whole-genome
amplifications that lead to lineage duplication in bacteria. Thus,
as Kimura predicted in 1968, it seems that neutral mechanisms
(non-adaptive processes) have had a preponderant role in evolution,
for which there is substantial evidence across species. This raises
the question of whether too much effort and many resources have
been devoted to studying adaptive evolution, which would correspond
to rare evolutionary processes, to the detriment of the majority of
changes that would occur in nature, which would be of a neutral
basis.
Biased vs stochastic changes in the genome
One of the main assumptions of seeing evolution as the 'survival of
the fittest' is that mutations emerge stochastically in the genome.
Once they emerge, according to this view, these mutations may or
may not confer a beneficial outcome to individuals within a
population. However, the mutations that will finally
prosper will be those that associate with a phenotype that confers
a reproductive advantage. Here, we can distinguish two processes,
(i) that of how genetic variation originates and (ii) that of how
it becomes evolutionary maintained
If we focus only on how genetic variation originates, many studies
have shown that mutations are indeed not stochastic in their
origins, rather they might be biased according to features within
the genome or reproduction. For example, GC-bias describes biased
conversion due to a distortion produced during the segregation of
gametes, in which G and C bases become over-represented with
regards to As and Ts. This process takes place during
recombination, during
Mesozoic
Epigenetics ___ _
which AT/GC heterozygotes end up producing more gametes carrying
G/C than A/T. GC-bias may occur in any region of the genome
(functional or not) and is known to have influenced GC content in
mammalian genomes. Biased conversions can also occur exclusively
out of the chemical nature of nucleotides. For example, it is well
known that transitions (A~G; C~T) always outnumber transversions
(A~C; A~T; C~G; G~T). This results in codon changes with increased
mutability of some amino acids (e.g. threonine and serine) and
reduced mutability of others (e.g. cysteine and tryptophan). In
addition, so-called epigenetic factors such as DNA methylation are
also known to bias mutation rates, as described below.
What is epigenetics?
Epigenetics is a term described by Conrad Waddington, a British
geneticist, who wanted to explain the meaning of epigenesis in a
genetic context. Epigenesis is a term that has been around since
Aristotelian times, and describes novel biological properties
(emergent properties) that arise within a developing embryo, and in
connection with the surrounding environment. In the 18th century,
the concept of epigenesis was seen to be in opposition to
'Preformation', which stated that all the components needed for the
embryo to become an adult individual were already present inside
the gametes. Epigenesis, in contrast to Preformation, proposes that
much of what happens during development is due to emergent
properties and the role of the surrounding environment, which in a
broad sense includes physical factors such as temperature, or
chemical factors such as hormones or inorganic chemicals.
Waddington posed the question "how do genes interact with their
products and the environment to bring phenotypes into being?" By
combining the term 'epigenesis' and 'genetics' he came up with a
term that is now becoming highly important in all fields of
biological sciences: 'epigenetics'.
One of the main concepts of epigenetics is to see the genome as a
reactive chemical entity rather than as a code directing the
development of organisms towards an adult phenotype. DNA is a
molecular structure, and as such, chemically interacts with an
array of other molecules; these can be complex molecules such as
proteins (histones), small fragments of RNA or simply methyl groups
that attach to the DNA structure. If the interaction of these
molecules with the DNA can be maintained even after cell divisions,
then they can be defined as epigenetic modifications. A remarkable
feature of epigenetic modifications is that on the one hand they
can regulate gene expression, while on the other hand they can be
influenced by environmental factors.
10 October 2017 © Biochemical Society
From epigenetic to genetic changes
DNA methylation is the enzymatic addition of a methyl group (-CH3)
to some nucleotides. Within the mammalian genome, the nucleotides
most affected by this chemical modification are Cs neighbouring Gs,
so-called CpG sites. The presence of methylation in regions of the
genome can regulate gene expression by interacting with
transcription factors that promote or repress gene
expression.
But, where do these methyl groups come from? Ultimately, they come
from our diet, from sources such as folic acid, betaine and vitamin
Bl2. Thus, the maintenance of the patterns of DNA methylation
during our lifetime will depend in part upon the dietary
availability of these ( and other) compounds.
One interesting aspect of DNA methylation is that it can be
regarded as a 'half mutation', because it is one hydrolytic
dearnination reaction short of a full conversion to T. Due to this,
the mutation rate of methylated CG dinudeotides (CpGs) to TGs is
increased by -12 times in comparison to the situation in which the
CpG is not methylated. This conversion, which is more frequent than
any other point mutation, is thought to contribute to the deficit
of CpGs observed in vertebrate genomes. Indeed, experiments in
bacteria (Escherichia coli) have shown that CpGs are hotspots of
mutations only when methylated.
Another connection between epigenetics and genomic variability
comes from genomic regions known as 'transposable repeat elements'
or transposons for short. The activity of transposons is generally
repressed by DNA methylation. However, if transposons become
active, duplications and insertions can be produced in the genome.
Interestingly, recent evidence has shown that transposition of
repeat elements played a crucial role in the genomic
diversification related to the radiation of African cichlid
fish.
Impact of epigenetic changes on genome variability and
evolution
In summary, the biochemical machinery of a cell contains the
necessary pathways that allow environmental agents to induce
mutations. Moreover, these pathways include the participation of
epigenetic modifications. However, can induced mutations mediated
by epigenetic mechanisms be evolutionarily maintained, or
relevant?
For epigenetically induced genetic modifications to be maintained
across generations, one aspect is needed: that they are
transgenerationally transmitted through the gametes. Recent
evidence has shown that when rodents are exposed to environmental
toxicants inside the womb, not only are epigenetic changes in the
gametes transmitted, but these can also induce genetic variability
as a consequence.
Now, even if these epigenetically induced mutations are maintained,
are they evolutionarily relevant? To answer this question, it is
important to go back to the concepts described at the beginning of
this article. According to neutral evolution, if these
epigenetically induced mutations are not detrimental for the
species or individuals, they will be evolutionarily maintained. If
that is the case, it should not be unthinkable that the
action of environmental agents, mediated by epigenetic mechanisms,
may be and may have been an important component in the generation
of genomic variability. Then the question becomes 'how much of the
genomic variability observed in nature mediated by epigenetic
mechanisms has emerged after being induced by environmental
conditions?' Answering this question will be an exciting scientific
exercise in the coming years, and might provide grounds to change
our general perception of evolution from the 'survival of the
fittest'
to the 'survival of the non-unfit'. •
Further reading
Brawand. D. Wagner, C.E., Li, Y.I. et al. (2014) The genomic
substrate for adaptive radiation in African
dchlid fish. Nature 513, 375-381
Collins, D.W. and Jukes, T .H. (1994) Rates of transition
and transversion in coding sequences since the
human-rodent divergence. Genomics 20, 386-396
Eyre-Walker, A. and Keightley, P.D. (2007) The
distribution of fitness effects of new mutations. Nat Rev. Genet.
•• 61 ()-618
Galtier, N. and Duret, L (2007) Adaptation or biased
gene conversion? Extending the null hypothesis of
molecular evolution. Trends Genet 23, 273-2n
Guerrero-Bosagna, C. (2012) Finalism in Darwinian
and Lamarckian evolution: lessons from epigenetics
and developmental biology. Evolutionary Biology 9,
283-300
a neutral view on epigenetic changes, genomic variability, and
evolutionary novelty. BloSclence, 67(5), 469-476
Kimura, M. (1991) Recent development of the neutral
theory viewed from the Wrightian tradition of theoretical
population genetics. Proc. Natl Acad. Sci.
USA II, 5969-5973
evolution: a review of recent evidence. Jpn J. Genet.
66, 367-386
Sweden. He has worked in environmental
epigenetics for over ten years, studying
epigenetic responses to environmental
chickens. His PhD was in Ecology and Evolutionary Biology
at the University of Chile, followed by post docs at Cornell
University, Washington State University and Linkoping
University. His research investigates the connection between
environment, epigenetic changes and adult phenotype,
by focusing specifically on studying how environmental
exposures interfere with reproduction, development and
epigenetic processes. His research has provided important
support for the concept of transgenerotional epigenetic
inheritance, which is the description of how environmental
influences can alter the germ line epigenome, thereby
affecting
the phenotypes of individuals in subsequent generations.
Email:
[email protected].
of epigenetlcs. Journal of Experimental Biology 211,
816-818
adaptive evolution within human non-coding
sequence. Hum. Mol. Genet 1 SSpec No 2. R17(}-175
Simrnen, M.W. (2008) Genome-scale relationships
between cytosine methylation and dinucleotide
abundances in animals. Genomics 92. 33-40
Sloan, 0.8.. Alverson, AJ. and OlucblcMak, J.P. (2012)
Rapid evolution of enormous, mwtidvomosomal
genomes in flowering plant mitochondria with
e,aptionally high mutation rates. PLo5 Biol 10, e 1001241
Smith, D.R. Hamaji. T. Olson, BJ. et al (2013)
Organelle genome complexity scales positively with
organism size in volvocine green algae. Mol Biol Evol.
30,793- 797
MM. (2015) Environmentally Induced epigenetic
transgeneratlonal lnherttance of sperm eplmutatlons
promote genetic mutations. Epigenetics 10, 762- 771
waddington. C. (1942) The eplgenotype. Endeavour 1, 18-20
Van Leuven, J.T. Meister, R.C. Simon. C. and
McCutcheon. J.P. (2014) Sympatrlc speciatlon in a
bacterial endosymbiont results in two genomes with
the functionality of one. Cell 151, 127(}-1280
October 2017 © Biochemical Society 11
