The chordate O. dioica, despite
losing lots of genes, maintains a typical body plan with organs and
structures (heart, brain, thyroids, etc.) which can be considered to be
homologues to the vertebrates.
Credit: Image courtesy of Universidad de Barcelona
"Loss is nothing else but change and
change is nature's delight" says the quote by the philosopher and
emperor Marcus Aurelius, which opens the scientific article that
analyses the gene loss phenomenon and its impact on the evolution of
living beings.
The study was published in the magazine Nature Review Genetics
and signed by professors Ricard Albalat and Cristian Cañestro, from the
Department of Genetics, Microbiology and Statistics and the
Biodiversity Research Institute (IRBio) of the University of Barcelona.
This article has just been selected as one of the recommended works with
special significance in genetics and genomics by the Faculty of 1000
Prime, an international ranking that identifies and re-evaluates the
best articles on biology and medicine with the support from a scientific
community of more than 10,000 academics worldwide.
Thinking of gene loss as an evolution force is a counterintuitive
idea, for it is easier to think that only when we gain something -genes
in this case- can we evolve. However the new work by these authors, who
are members of the Research Group on Evolution and Development
(EVO-DEVO) of the UB, paints the vision of gene loss as a great
potential process of genetic change and evolutionary adaption.
Losing genes is also an evolution engine
A gene is lost when the genome is physically removed (by illegitimate
recombination, transposition, etc.) or when it is still in the genome
but with no use due to a mutation (particular changes, insertions,
deficiencies, etc.). "The genome sequencing of very different organisms
has shown that gene loss has been a usual phenomenon during evolution in
all life cycles. In some cases, it has been proven that this loss might
mean an adaptive response towards stressful situations when facing
sudden environmental changes" says Professor Cristian Cañestro.
"In other cases, there are genetic losses -says Cañestro- which even
though they are neutral per se, have contributed to the genetic and
reproductive isolation among lineages, and thus, to speciation, or have
rather participated in the sexual differentiation in contributing to the
creation of a new Y chromosome. The fact that genetic loss patterns are
not stochastic but rather biased in the lost genes (depending on the
kind of function of the gene or its situation in the genome in different
organism groups) stresses the importance of the genetic loss in the
evolution of the species.
Losing to win: an evolutionary paradox
Traditionally, it was believed that insects tended to lose genes. However, the genome sequencing of a beetle (Tribolium castaneum),
which proves to have few gene losses, has made it worth reconsidering.
In the chordates phylum, which includes vertebrates, there are also some
differences among the species, with particular cases such as the
planktonic organism Oikopleura dioica -- very prone to gene loss.
According to Professor Ricard Albalat, "it has been shown that the
possibility of losing genes is linked to the lifestyle of the species.
Parasites, for instance, show a greater tendency of gene loss because
since they re-use their host's resources, lots of their genes become
dispensable and end up disappearing. Species with lots of redundant
genes such as the vertebrates and lots of plant species and yeasts which
have doubled their genome, have also suffered from gene loss over the
course of evolution.
"Interestingly -says Albalat- the massive gene losses are not always
linked to radical morphological changes in the affected organism's body
plan. The chordate Oikopleura dioica, for example, despite losing lots
of genes -some are essential to the embryo development and design of the
phylum body plan- maintains a typical body plan with organs and
structures (heart, brain, thyroids, etc.) which can be considered to be
homologues to the vertebrates'. However, this contradiction, which we
have defined as "inverse paradox" of EvoDevo, is still very difficult to
explain."
Lost genes in the human evolutionary history
Gene loss can become a positive condition. This has been proved with
laboratory experiments (in yeast or bacteria) and population studies on
humans. Some of the best studied cases on humans are coding gene losses
with cell receptors (CCR5 and DUFFY), which make individuals more
resistant to HIV infection and to plasmodium caused by malaria. In
nature, there are gene losses from which some organisms benefited:
losses which made colour changes in flowers which attract new
pollinators, losses which made warmness-resistant insects to be able to
colonize new habitats, etc.
Some studies also suggest that gene loss has been decisive in the
origins of the human species. Chimpanzees and humans share more than the
98% of their genome -something which has always been of great interest-
and in this context it is tempting to speculate that perhaps it would
be necessary to look for the differences not in the shared genes but in
the lost ones- the ones which have been lost in a different way through
the human and primate evolution. "For example, it is believed that gene
loss reduced the jaw muscular structure, which allowed the human brain
to grow its size, or that gene losses were important in the improvement
of our defence system against illnesses," says Cristian Cañestro.
How many genes can a living being lose?
A gene can be lost only if it is dispensable and, therefore, its loss
doesn't involve a disadvantage for the individuals. What makes a gene
to be dispensable? A gene becomes dispensable when the organism can do
its function in an alternative way (functional redundancy) or when the
gene is no longer needed because the organism lost its structure or the
physiologic requirement in which the gene participated (regressive
evolution). For this reason, some changes in the species' lifestyle can
turn some genes dispensable, as seen in the gene loss related to
pigmentation and vision of the species who adopted cave-dweller ways of
life.
Discovering how many genes an organism can lose and how, is something
essential to understand how many human genes are dispensable and why
certain mutations are irrelevant while others are dramatic for our
health. Actually, the recent genome sequencing in individuals from
several communities around the world has shown that any healthy person
has an average amount of 20 genes not working and it does not seem to
provoke any unfavourable consequence.
When genes are dispensable: less is more
According to Ricard Albalat, "probably, the presences of redundant
genes or environmental conditions in which we live make us to have less
unnecessary genes. Researching on the differences of gene losses among
different human communities has allowed, for instance, discovering that
lipoprotein A gene loss grants resistance to coronary illnesses among
the Finnish population who have fat-rich diets. This experimental
approach which relates genes to diseases, called "genotype first," opens
the door to the discovery of genes which, when disappearing, give an
advantage towards some environmental tensions (diets, climate, toxics,
pathogens, etc.) and therefore it could help identifying new genes with
therapeutic interests."
Oikopleura dioica: a new model organism in UB's research
Promoting basic research with model organisms (bacteria, mice, yeast, plants, zebrafish, Drosophila or C. elegans)
has been a key fact to promote the progress in the field of biomedicine
and health. For the scientists, one 21th Century challenge is to
develop animal models alternative to the classic ones which can enable
applying massive sequencing technologies or also genetic systematic
modifications to open new perspectives in the field of basic research.
Only by creating basic knowledge is it possible to improve with
society's wellbeing.
Nowadays the Evo-Devo-Genomics team of the UB is one of the few research groups around the world which studies the Oikopleura dioica
from an evolutionary developmental biology perspective (Evo-Devo). This
is also the only team in Spain which has launched a scientific
infrastructure -there are two more in Bergen (Norway) and Osaka (Japan)-
considered as an international projecting referent with the ability of
developing and studying this new model organism.
The Oikopleura dioica is a small animal, with a short life
cycle, very prolific and easy to keep in the laboratory. These
conditions make it an excellent model animal. Its genome, sequenced, is
extraordinarily compact -three times smaller than the one of the
Drosophila fly- and has lost a lot of genes. Currently, the UB experts
use O. dioica as evolution mutant which has lots important genes for the
embryo development. The research group works in two research lines. On
the one hand, they use O. dioica to research on the toxic
compound effect in marine animal development and reproduction, as well
as its impact on the ocean trophic chains. On the other hand, they use O. dioica to study how genetic losses have affected the cardio development mechanisms.
"We hope these studies enable us to identify the essential 'minimum
gene set' to produce a heart, and would help us understand better the
genetic basics of certain cardiomyopathies and discover new genes to
improve the diagnosis" say Ricard Albalat and Cristian Cañestro.