A heterozygote advantage describes the case in which the heterozygousgenotype has a higher relative fitness than either the homozygousdominant or homozygous recessive genotype. The specific case of heterozygote advantage due to a single locus is known as overdominance. Overdominance is a condition in genetics where the phenotype
of the heterozygote lies outside of the phenotypical range of both
homozygote parents, and heterozygous individuals have a higher fitness than homozygous individuals.
Polymorphism can be maintained by selection favoring the heterozygote, and this mechanism is used to explain the occurrence of some kinds of genetic variability.
A common example is the case where the heterozygote conveys both
advantages and disadvantages, while both homozygotes convey a
disadvantage. A well-established case of heterozygote advantage is that
of the gene involved in sickle cell anaemia.
Often, the advantages and disadvantages conveyed are rather complicated, because more than one gene may influence a given trait or morph. Major genes almost always have multiple effects (pleiotropism),
which can simultaneously convey separate advantageous traits and
disadvantageous traits upon the same organism. In this instance, the
state of the organism's environment will provide selection,
with a net effect either favoring or working in opposition to the gene,
until an environmentally determined equilibrium is reached.
Heterozygote advantage is a major underlying mechanism for heterosis,
or "hybrid vigor", which is the improved or increased function of any
biological quality in a hybrid offspring. Previous research, comparing
measures of dominance, overdominance and epistasis (mostly in plants),
found that the majority of cases of heterozygote advantage were due to
complementation (or dominance), the masking of deleterious recessive
alleles by wild-type alleles, as discussed in the articles Heterosis and Complementation (genetics), but there were also findings of overdominance, especially in rice. More recent research, however, has established that there is also an epigenetic contribution to heterozygote advantage, primarily as determined in plants, though also reported in mice.
In theory
When
two populations of any sexual organism are separated and kept isolated
from each other, the frequencies of deleterious mutations in the two
populations will differ over time, by genetic drift.
It is highly unlikely, however, that the same deleterious mutations
will be common in both populations after a long period of separation.
Since loss-of-function mutations tend to be recessive (given that
dominant mutations of this type generally prevent the organism from
reproducing and thereby passing the gene on to the next generation), the
result of any cross between the two populations will be fitter than the parent.
This article deals with the specific case of fitness overdominance, where the fitness advantage of the cross is caused by being heterozygous at one specific locus alone.
Experimental confirmation
Cases
of heterozygote advantage have been demonstrated in several organisms,
including humans. The first experimental confirmation of heterozygote
advantage was with Drosophila melanogaster, a fruit fly that has been a model organism for genetic research. In a classic study, Kalmus demonstrated how polymorphism can persist in a population through heterozygote advantage.
If weakness were the only effect of the mutant allele, so it
conveyed only disadvantages, natural selection would weed out this
version of the gene until it became extinct from the population.
However, the same mutation also conveyed advantages, providing improved
viability for heterozygous individuals. The heterozygote expressed none
of the disadvantages of homozygotes, yet gained improved viability. The
homozygote wild type
was perfectly healthy, but did not possess the improved viability of
the heterozygote, and was thus at a disadvantage compared to the
heterozygote in survival and reproduction.
This mutation, which at first glance appeared to be harmful,
conferred enough of an advantage to heterozygotes to make it beneficial,
so that it remained at dynamic equilibrium in the gene pool. Kalmus
introduced flies with the ebony mutation to a wild-type population. The
ebony allele persisted through many generations of flies in the study,
at genotype frequencies that varied from 8% to 30%. In experimental
populations, the ebony allele was more prevalent and therefore
advantageous when flies were raised at low, dry temperatures, but less
so in warm, moist environments.
In human genetics
Sickle-cell anemia
Sickle-cell anemia (SCA) is a genetic disorder caused by the presence of two incompletely recessive alleles. When a sufferer's red blood cells are exposed to low-oxygen
conditions, the cells lose their healthy round shape and become
sickle-shaped. This deformation of the cells can cause them to become
lodged in capillaries, depriving other parts of the body of sufficient
oxygen. When untreated, a person with SCA may suffer from painful
periodic bouts, often causing damage to internal organs, strokes, or anemia. Typically, the disease results in premature death.
Because the genetic disorder is incompletely recessive, a person
with only one SCA allele and one unaffected allele will have a "mixed" phenotype: The sufferer will not experience the ill effects of the disease, yet will still possess a sickle cell trait,
whereby some of the red blood cells undergo benign effects of SCA, but
nothing severe enough to be harmful. Those afflicted with sickle-cell
trait are also known as carriers: If two carriers have a child, there is
a 25% chance their child will have SCA, a 50% chance their child will
be a carrier, and a 25% chance that the child will neither have SCA nor
be a carrier. Were the presence of the SCA allele to confer only
negative traits, its allele frequency would be expected to decrease
generation after generation, until its presence were completely
eliminated by selection and by chance.
However, convincing evidence indicates, in areas with persistent malaria
outbreaks, individuals with the heterozygous state have a distinct
advantage (and this is why individuals with heterozygous alleles are far
more common in these areas).
Those with the benign sickle trait possess a resistance to malarial
infection. The pathogen that causes the disease spends part of its cycle
in the red blood cells and triggers an abnormal drop in oxygen levels
in the cell. In carriers, this drop is sufficient to trigger the full
sickle-cell reaction, which leads to infected cells being rapidly
removed from circulation and strongly limiting the infection's progress.
These individuals have a great resistance to infection and have a
greater chance of surviving outbreaks. However, those with two alleles
for SCA may survive malaria, but will typically die from their genetic
disease unless they have access to advanced medical care. Those of the
homozygous "normal" or wild-type case will have a greater chance of
passing on their genes successfully, in that there is no chance of their
offspring's suffering from SCA; yet, they are more susceptible to dying
from malarial infection before they have a chance to pass on their
genes.
This resistance to infection is the main reason the SCA allele
and SCA disease still exist. It is found in greatest frequency in
populations where malaria was and often still is a serious problem. Approximately one in 10 African Americans is a carrier,
as their recent ancestry is from malaria-stricken regions. Other
populations in Africa, India, the Mediterranean and the Middle East have
higher allele frequencies, as well. As effective antimalarial treatment
becomes increasingly available to malaria-stricken populations, the
allele frequency for SCA is expected to decrease, so long as SCA
treatments are unavailable or only partially effective. If effective
sickle-cell anemia treatments become available to the same degree,
allele frequencies should remain at their present levels in these
populations. In this context, 'treatment effectiveness' refers to the
reproductive fitness it grants, rather than the degree of suffering
alleviation.
Cystic fibrosis
Cystic fibrosis (CF) is an autosomal recessive hereditary monogenic disease of the lungs, sweat glands and digestive system. The disorder is caused by the malfunction of the CFTR protein, which controls intermembrane transport of chloride
ions, which is vital to maintaining equilibrium of water in the body.
The malfunctioning protein causes viscous mucus to form in the lungs and
intestinal tract. Before modern times, children born with CF would have
a life expectancy of only a few years, but modern medicine has made it
possible for these people to live into adulthood. However, even in these
individuals, CF typically causes male infertility. It is the most common genetic disease among people of European descent.
The presence of a single CF mutation may influence survival of
people affected by diseases involving loss of body fluid, typically due
to diarrhea. The most common of these maladies is cholera,
which only began killing Europeans millennia after the CF mutation
frequency was already established in the population. Another such
disease that CF may protect against is typhoid.
Those with cholera would often die of dehydration due to intestinal
water losses. A mouse model of CF was used to study resistance to
cholera, and the results were published in Science in 1994
(Gabriel, et al.). The heterozygote (carrier) mouse had less secretory
diarrhea than normal, noncarrier mice. Thus, it appeared for a time that
resistance to cholera explained the selective advantage to being a
carrier for CF and why the carrier state was so frequent.
This theory has been called into question. Hogenauer, et al.
have challenged this popular theory with a human study. Prior data were
based solely on mouse experiments. These authors found the heterozygote
state was indistinguishable from the noncarrier state.
Another theory for the prevalence of the CF mutation is that it provides resistance to tuberculosis.
Tuberculosis was responsible for 20% of all European deaths between
1600 and 1900, so even partial protection against the disease could
account for the current gene frequency.
The most recent hypothesis, published in the Journal of
Theoretical Biology, proposed having a single CF mutation granted
respiratory advantage for early Europeans migrating north into the dusty
wasteland left by the Last Glacial Maximum.
As of 2016, the selective pressure for the high gene prevalence
of CF mutations is still uncertain, and may be due to an unbiased
genetic drift rather than a selective advantage. Approximately one in 25
persons of European descent is a carrier of the disease, and one in
2500 to 3000 children born is affected by Cystic fibrosis.
Triosephosphate isomerase
Triosephosphate isomerase (TPI) is a central enzyme of glycolysis, the main pathway for cells to obtain energy by metabolizing sugars. In humans, certain mutations within this enzyme, which affect the dimerisation of this protein, are causal for a rare disease, triosephosphate isomerase deficiency. Other mutations, which inactivate the enzyme (= null alleles) are lethal when inherited homozygously (two defective copies of the TPI gene), but have no obvious effect in heterozygotes
(one defective and one normal copy). However, the frequency of
heterozygous null alleles is much higher than expected, indicating a
heterozygous advantage for TPI null alleles. The reason is unknown;
however, new scientific results are suggesting cells having reduced TPI
activity are more resistant against oxidative stress. PlosOne, Dec. 2006
Resistance to hepatitis C virus infection
There
is evidence that genetic heterozygosity in humans provides increased
resistance to certain viral infections. A significantly lower proportion
of HLA-DRB1 heterozygosity exists among HCV-infected cases than
uninfected cases. The differences were more pronounced with alleles
represented as functional supertypes (P = 1.05 × 10−6) than those represented as low-resolution genotypes (P = 1.99 × 10−3).
These findings constitute evidence that heterozygosity provides an
advantage among carriers of different supertype HLA-DRB1 alleles against
HCV infection progression to end-stage liver disease in a large-scale,
long-term study population.
MHC heterozygosity and human scent preferences
Multiple studies have shown, in double-blind experiments, females prefer the scent of males who are heterozygous at all three MHC loci.
The reasons proposed for these findings are speculative; however, it
has been argued that heterozygosity at MHC loci results in more alleles
to fight against a wider variety of diseases, possibly increasing
survival rates against a wider range of infectious diseases.
The latter claim has been tested in an experiment, which showed
outbreeding mice to exhibit MHC heterozygosity enhanced their health and
survival rates against multiple-strain infections.
BAFF and autoimmune disease
B-cell activating factor
(BAFF) is a cytokine encoded by the TNFSF13B gene. A variant of the
gene containing a deletion (GCTGT—>A) renders a shorter mRNA
transcript that escapes degradation by microRNA,
thus increasing expression of BAFF, which consequently up-regulates the
humoral immune response. This variant is associated with systemic lupus erythematosus and multiple sclerosis, but heterozygote carriers of the variant have decreased susceptibility to malaria infection.
In the 1980s, the American palaeontologists Stephen Jay Gould and Niles Eldredge argued for an extended synthesis based on their idea of punctuated equilibrium, the role of species selection shaping large scale evolutionary patterns and natural selection working on multiple levels extending from genes to species.
The ethologist John Endler wrote a paper in 1988 discussing processes of evolution that he felt had been neglected.
Contributions from evolutionary developmental biology
Some researchers in the field of evolutionary developmental biology proposed another synthesis. They argue that the modern and extended syntheses should mostly center on genes and suggest an integration of embryology with molecular genetics an evolution, aiming to understand how natural selection operates on gene regulation and deep homologies between organisms at the level of highly conserved genes, transcription factors and signalling pathways. By contrast, a different strand of evo-devo following an organismal approach contributes to the extended synthesis by emphasizing (amongst others) developmental bias (both through facilitation and constraint), evolvability, and inherency of form as primary factors in the evolution of complex structures and phenotypic novelties.
Recent history
Massimo Pigliucci, a leading proponent of the extended evolutionary synthesis in its 2007 form
The idea of an extended synthesis was relaunched in 2007 by Massimo Pigliucci, and Gerd B. Müller with a book in 2010 titled Evolution: The Extended Synthesis, which has served as a launching point for work on the extended synthesis. This includes:
The role of prior configurations, genomic structures, and other traits in the organism in generating evolutionary variations.
How increasing dimensionality of fitness landscapes affects our view of speciation.
How organisms modify the environments they belong to through niche construction.
Other processes such as evolvability, phenotypic plasticity, reticulate evolution, sex evolution and symbiogenesis are said by proponents to have been excluded or missed from the modern synthesis. The goal of Piglucci's and Müller's extended synthesis is to take evolution beyond the gene-centered approach
of population genetics to consider more organism- and ecology-centered
approaches. Many of these causes are currently considered secondary in
evolutionary causation, and proponents of the extended synthesis want
them to be considered first-class evolutionary causes. The biologist Eugene Koonin
wrote in 2009 that "the new developments in evolutionary biology by no
account should be viewed as refutation of Darwin. On the contrary, they
are widening the trails that Darwin blazed 150 years ago and reveal the
extraordinary fertility of his thinking."
Predictions
The
extended synthesis is characterized by its additional set of
predictions that differ from the standard modern synthesis theory:
rapid evolution can result from simultaneous induction, natural selection and developmental dynamics
biodiversity can be affected by features of developmental systems such as differences in evolvability
heritable variation is directed towards variants that are adaptive and integrated with phenotype
niche construction
is biased towards environmental changes that suit the constructor's
phenotype, or that of its descendants, and enhance their fitness
The
extended evolutionary synthesis is currently being tested by a group of
scientists from eight institutions in Britain, Sweden and the United
States. The £7.7 million project is supported by a £5.7 million grant
from the John Templeton Foundation.
The project is headed by Kevin N. Laland at the University of St Andrews and Tobias Uller at Lund University.
According to Laland what the extended synthesis "really boils down to
is recognition that, in addition to selection, drift, mutation and other
established evolutionary processes, other factors, particularly
developmental influences, shape the evolutionary process in important
ways."
Status
Biologists
disagree on the need for an extended synthesis. Opponents contend that
the modern synthesis is able to fully account for the newer
observations, whereas others criticize that the Extended synthesis is
not radical enough. Proponents think that the conceptions of evolution at the core of the modern synthesis are too narrow.
Proponents argue that even when the modern synthesis allows for the
ideas in the extended synthesis, using the modern synthesis affects the
way that biologists think about evolution. For example, Denis Noble
says that using terms and categories of the modern synthesis distort
the picture of biology that modern experimentation has discovered.
Proponents therefore claim that the extended synthesis is necessary to
help expand the conceptions and framework of how evolution is considered
throughout the biological disciplines.
Evolvability is defined as the capacity of a system for adaptive evolution. Evolvability is the ability of a population of organisms to not merely generate genetic diversity, but to generate adaptive genetic diversity, and thereby evolve through natural selection.
In order for a biological organism to evolve by natural
selection, there must be a certain minimum probability that new,
heritable variants are beneficial. Random mutations, unless they occur in DNA sequences with no function, are expected to be mostly detrimental. Beneficial mutations are always rare, but if they are too rare, then adaptation cannot occur. Early failed efforts to evolve computer programs by random mutation and selection showed that evolvability is not a given, but depends on the representation of the program. Analogously, the evolvability of organisms depends on their genotype–phenotype map. This means that genomes
are structured in ways that make beneficial changes less unlikely. This
has been taken as evidence that evolution has created not just fitter
organisms, but populations of organisms that are better able to evolve.
Alternative definitions
Andreas Wagner describes two definitions of evolvability. According to the first definition, a biological system is evolvable:
if its properties show heritable genetic variation, and
if natural selection can thus change these properties.
According to the second definition, a biological system is evolvable:
if it can acquire novel functions through genetic change, functions that help the organism survive and reproduce.
For example, consider an enzyme with multiple alleles
in the population. Each allele catalyzes the same reaction, but with a
different level of activity. However, even after millions of years of
evolution, exploring many sequences with similar function, no mutation
might exist that gives this enzyme the ability to catalyze a different
reaction. Thus, although the enzyme's activity is evolvable in the first
sense, that does not mean that the enzyme's function is evolvable in
the second sense. However, every system evolvable in the second sense
must also be evolvable in the first.
Pigliucci
recognizes three classes of definition, depending on timescale. The
first corresponds to Wagner's first, and represents the very short
timescales that are described by quantitative genetics.
He divides Wagner's second definition into two categories, one
representing the intermediate timescales that can be studied using population genetics, and one representing exceedingly rare long-term innovations of form.
Pigliucci's second definition of evolvability includes Altenberg's
quantitative concept of evolvability, being not a single number, but
the entire upper tail of the fitness distribution of the offspring
produced by the population. This quantity was considered a "local"
property of the instantaneous state of a population, and its integration
over the population's evolutionary trajectory, and over many possible
populations, would be necessary to give a more global measure of
evolvability.
Generating more variation
More
heritable phenotypic variation means more evolvability. While mutation
is the ultimate source of heritable variation, its permutations and
combinations also make a big difference. Sexual reproduction generates
more variation (and thereby evolvability) relative to asexual
reproduction (see evolution of sexual reproduction). Evolvability is further increased by generating more variation when an organism is stressed,
and thus likely to be less well adapted, but less variation when an
organism is doing well. The amount of variation generated can be
adjusted in many different ways, for example via the mutation rate, via the probability of sexual vs. asexual reproduction, via the probability of outcrossing vs. inbreeding, via dispersal, and via access to previously cryptic variants through the switching of an evolutionary capacitor. A large population size increases the influx of novel mutations each generation.
Enhancement of selection
Rather
than creating more phenotypic variation, some mechanisms increase the
intensity and effectiveness with which selection acts on existing
phenotypic variation. For example:
Large effective population size increasing the threshold value of the selection coefficient
above which selection becomes an important player. This could happen
through an increase in the census population size, decreasing genetic drift, through an increase in the recombination rate, decreasing genetic draft, or through changes in the probability distribution of the numbers of offspring..
Recombination decreasing the importance of the Hill-Robertson effect,
where different genotypes contain different adaptive mutations.
Recombination brings the two alleles together, creating a super-genotype
in place of two competing lineages..
Shorter generation time.
Robustness and evolvability
The relationship between robustness and evolvability depends on whether recombination can be ignored. Recombination can generally be ignored in asexual populations and for traits affected by single genes.
Without recombination
Robustness in the face of mutation
does not increase evolvability in the first sense. In organisms with a
high level of robustness, mutations have smaller phenotypic effects than
in organisms with a low level of robustness. Thus, robustness reduces
the amount of heritable genetic variation on which selection can act.
However, robustness may allow exploration of large regions of genotype space, increasing evolvability according to the second sense.
Even without genetic diversity, some genotypes have higher evolvability
than others, and selection for robustness can increase the
"neighborhood richness" of phenotypes that can be accessed from the same
starting genotype by mutation. For example, one reason many proteins
are less robust to mutation is that they have marginal thermodynamic stability,
and most mutations reduce this stability further. Proteins that are
more thermostable can tolerate a wider range of mutations and are more
evolvable.
For polygenic traits, neighborhood richness contributes more to
evolvability than does genetic diversity or "spread" across genotype
space.
With recombination
Temporary robustness, or canalisation,
may lead to the accumulation of significant quantities of cryptic
genetic variation. In a new environment or genetic background, this
variation may be revealed and sometimes be adaptive.
Exploration ahead of time
When mutational robustness
exists, many mutants will persist in a cryptic state. Mutations tend to
fall into two categories, having either a very bad effect or very
little effect: few mutations fall somewhere in between. Sometimes, these mutations will not be completely invisible, but still have rare effects, with very low penetrance. When this happens, natural selection weeds out the very bad mutations, while leaving the others relatively unaffected.
While evolution has no "foresight" to know which environment will be
encountered in the future, some mutations cause major disruption to a
basic biological process, and will never be adaptive in any environment.
Screening these out in advance leads to preadapted stocks of cryptic genetic variation.
Another way that phenotypes can be explored, prior to strong
genetic commitment, is through learning. An organism that learns gets to
"sample" several different phenotypes during its early development, and
later sticks to whatever worked best. Later in evolution, the optimal
phenotype can be genetically assimilated so it becomes the default behavior rather than a rare behavior. This is known as the Baldwin effect, and it can increase evolvability.
Learning biases phenotypes in a beneficial direction. But an exploratory flattening of the fitness landscape
can also increase evolvability even when it has no direction, for
example when the flattening is a result of random errors in molecular
and/or developmental processes. This increase in evolvability can happen
when evolution is faced with crossing a "valley" in an adaptive landscape.
This means that two mutations exist that are deleterious by themselves,
but beneficial in combination. These combinations can evolve more
easily when the landscape is first flattened, and the discovered
phenotype is then fixed by genetic assimilation.
Modularity
If
every mutation affected every trait, then a mutation that was an
improvement for one trait would be a disadvantage for other traits. This
means that almost no mutations would be beneficial overall. But if pleiotropy is restricted to within functional modules,
then mutations affect only one trait at a time, and adaptation is much
less constrained. In a modular gene network, for example, a gene that
induces a limited set of other genes that control a specific trait under
selection may evolve more readily than one that also induces other gene
pathways controlling traits not under selection.
Individual genes also exhibit modularity. A mutation in one
cis-regulatory element of a gene's promoter region may allow the
expression of the gene to be altered only in specific tissues,
developmental stages, or environmental conditions rather than changing
gene activity in the entire organism simultaneously.
Evolution of evolvability
While
variation yielding high evolvability could be useful in the long term,
in the short term most of that variation is likely to be a disadvantage.
For example, naively it would seem that increasing the mutation rate
via a mutator allele would increase evolvability. But as an extreme
example, if the mutation rate is too high then all individuals will be
dead or at least carry a heavy mutation load. Short-term selection for low variation most of the time is usually thought
likely to be more powerful than long-term selection for evolvability,
making it difficult for natural selection to cause the evolution of
evolvability. Other forces of selection also affect the generation of
variation; for example, mutation and recombination may in part be
byproducts of mechanisms to cope with DNA damage.
When recombination is low, mutator alleles may still sometimes hitchhike on the success of adaptive mutations that they cause. In this case, selection can take place at the level of the lineage. This may explain why mutators are often seen during experimental evolution
of microbes. Mutator alleles can also evolve more easily when they only
increase mutation rates in nearby DNA sequences, not across the whole
genome: this is known as a contingency locus.
The evolution of evolvability is less controversial if it occurs via the evolution of sexual reproduction, or via the tendency of variation-generating mechanisms to become more active when an organism is stressed. The yeast prion [PSI+] may also be an example of the evolution of evolvability through evolutionary capacitance. An evolutionary capacitor is a switch that turns genetic variation on and off. This is very much like bet-hedging the risk that a future environment will be similar or different. Theoretical models also predict the evolution of evolvability via modularity.
When the costs of evolvability are sufficiently short-lived, more
evolvable lineages may be the most successful in the long-term.
However, the hypothesis that evolvability is an adaptation is often
rejected in favor of alternative hypotheses, e.g. minimization of costs.
Applications
Evolvability phenomena have practical applications. For protein engineering
we wish to increase evolvability, and in medicine and agriculture we
wish to decrease it. Protein evolvability is defined as the ability of
the protein to acquire sequence diversity and conformational flexibility
which can enable it to evolve toward a new function.
In protein engineering, both rational design and directed evolution approaches aim to create changes rapidly through mutations with large effects. Such mutations, however, commonly destroy enzyme function or at least reduce tolerance to further mutations.
Identifying evolvable proteins and manipulating their evolvability is
becoming increasingly necessary in order to achieve ever larger
functional modification of enzymes.
Proteins are also often studied as part of the basic science of
evolvability, because the biophysical properties and chemical
functions can be easily changed by a few mutations.
More evolvable proteins can tolerate a broader range of amino acid
changes and allow them to evolve toward new functions. The study of
evolvability has fundamental importance for understanding very long term
evolution of protein superfamilies.
Many human diseases are capable of evolution. Viruses, bacteria, fungi and cancers evolve to be resistant to host immune defences, as well as pharmaceutical drugs. These same problems occur in agriculture with pesticide and herbicide resistance. It is possible that we are facing the end of the effective life of most of available antibiotics. Predicting the evolution and evolvability
of our pathogens, and devising strategies to slow or circumvent the
development of resistance, demands deeper knowledge of the complex
forces driving evolution at the molecular level.
Fertilisation or fertilization, also known as generative fertilisation, insemination, pollination, fecundation, syngamy and impregnation, is the fusion of gametes to initiate the development of a new individual organism. The cycle of fertilisation and development of new individuals is called sexual reproduction.
During double fertilisation in angiosperms the haploid male gamete
combines with two haploid polar nuclei to form a triploid primary
endosperm nucleus by the process of vegetative fertilisation.
History
In Antiquity, Aristotle
conceived the formation of new individuals through fusion of male and
female fluids, with form and function emerging gradually, in a mode
called by him as epigenetic.
In 1784, Spallanzani established the need of interaction between the female's ovum and male's sperm to form a zygote in frogs. In 1827, von Baer observed a mammalian egg for the first time. Oscar Hertwig (1876), in Germany, described the fusion of nuclei of spermatozoa and of ova from sea urchin.
Evolution
The evolution of fertilisation is related to the origin of meiosis, as both are part of sexual reproduction, originated in eukaryotes.
There are two conflicting theories on how the couple
meiosis–fertilisation arose. One is that it evolved from prokaryotic sex
(bacterial recombination) as eukaryotes evolved from prokaryotes. The other is that mitosis originated meiosis.
Fertilisation in plants
In the Bryophyte land plants, fertilisation takes place within the archegonium. This moss has been genetically modified so that the unfertilised egg within the archegonium produces a blue colour.
The
gametes that participate in fertilisation of plants are the pollen
(male), and the egg (female) cell. Various families of plants have
differing methods by which the female gametophyte is fertilized. In Bryophyte land plants, fertilisation takes place within the archegonium. In flowering plants a second fertilisation event involves another sperm cell and the central cell which is a second female gamete. In flowering plants there are two sperm from each pollen grain.
Unlike animal sperm which is motile, plant sperm is immotile and
relies on the pollen tube to carry it to the ovule where the sperm is
released. The pollen tube penetrates the stigma
and elongates through the extracellular matrix of the style before
reaching the ovary. Then near the receptacle, it breaks through the ovule through the micropyle (an opening in the ovule wall) and the pollen tube "bursts" into the embryo sac, releasing sperm.
The growth of the pollen tube has been believed to depend on chemical
cues from the pistil, however these mechanisms were poorly understood
until 1995. Work done on tobacco plants revealed a family of glycoproteins called TTS proteins that enhanced growth of pollen tubes.
Pollen tubes in a sugar free pollen germination medium and a medium
with purified TTS proteins both grew. However, in the TTS medium, the
tubes grew at a rate 3x that of the sugar-free medium. TTS proteins were also placed on various locations of semi in vevo
pollinated pistils, and pollen tubes were observed to immediately
extend toward the proteins. Transgenic plants lacking the ability to
produce TTS proteins exhibited slower pollen tube growth and reduced
fertility.
Rupture of pollen tube
The rupture of the pollen tube to release sperm in Arabidopsis
has been shown to depend on a signal from the female gametophyte.
Specific proteins called FER protein kinases present in the ovule
control the production of highly reactive derivatives of oxygen called reactive oxygen species (ROS). ROS levels have been shown via GFP
to be at their highest during floral stages when the ovule is the most
receptive to pollen tubes, and lowest during times of development and
following fertilization.
High amounts of ROS activate Calcium ion channels in the pollen
tube, causing these channels to take up Calcium ions in large amounts.
This increased uptake of calcium causes the pollen tube to rupture, and
release its sperm into the ovule. Pistil feeding assays in which plants were fed diphenyl iodonium chloride (DPI) suppressed ROS concentrations in Arabidopsis, which in turn prevented pollen tube rupture.
Bryophytes
Bryophyte
is a traditional name used to refer to all embryophytes (land plants)
that do not have true vascular tissue and are therefore called
"non-vascular plants". Some bryophytes do have specialised tissues for
the transport of water; however, since these do not contain lignin, they
are not considered true vascular tissue.
Ferns
A fern is a
member of a group of roughly 12,000 species of vascular plants that
reproduce via spores and have neither seeds nor flowers. They differ
from mosses by being vascular (i.e. having water-conducting vessels).
They have stems and leaves, like other vascular plants. Most ferns have
what are called fiddleheads that expand into fronds, which are each
delicately divided.
Gymnosperms
The gymnosperms are a group of seed producing plants that includes conifers, Cycads, Ginkgo, and Gnetales.
The term "gymnosperm" comes from the Greek composite word γυμνόσπερμος
(γυμνός gymnos, "naked" and σπέρμα sperma, "seed"), meaning "naked
seeds", after the unenclosed condition of their seeds (called ovules in
their unfertilised state). Their naked condition stands in contrast to
the seeds and ovules of flowering plants (angiosperms), which are
enclosed within an ovary. Gymnosperm seeds develop either on the surface
of scales or leaves, often modified to form cones, or at the end of
short stalks as in Ginkgo.
Flowering plants
After being fertilised, the ovary starts to swell and develop into the fruit.
With multi-seeded fruits, multiple grains of pollen are necessary for
syngamy with each ovule. The growth of the pollen tube is controlled by
the vegetative (or tube) cytoplasm. Hydrolytic enzymes
are secreted by the pollen tube that digest the female tissue as the
tube grows down the stigma and style; the digested tissue is used as a
nutrient source for the pollen tube as it grows. During pollen tube
growth towards the ovary, the generative nucleus divides to produce two
separate sperm nuclei (haploid number of chromosomes) – a growing pollen tube therefore contains three separate nuclei, two sperm and one tube.
The sperms are interconnected and dimorphic, the large one, in a number
of plants, is also linked to the tube nucleus and the interconnected
sperm and the tube nucleus form the "male germ unit".
Double fertilisation is the process in angiosperms (flowering plants) in which two sperm from each pollen tube fertilise two cells in a female gametophyte
(sometimes called an embryo sac) that is inside an ovule. After the
pollen tube enters the gametophyte, the pollen tube nucleus
disintegrates and the two sperm cells are released; one of the two sperm
cells fertilises the egg cell (at the bottom of the gametophyte near the micropyle), forming a diploid (2n) zygote.
This is the point when fertilisation actually occurs; pollination and
fertilisation are two separate processes. The nucleus of the other sperm
cell fuses with two haploid polar nuclei (contained in the central
cell) in the centre of the gametophyte. The resulting cell is triploid (3n). This triploid cell divides through mitosis and forms the endosperm, a nutrient-rich tissue, inside the seed.
The two central-cell maternal nuclei (polar nuclei) that
contribute to the endosperm arise by mitosis from the single meiotic
product that also gave rise to the egg. Therefore, maternal contribution
to the genetic constitution of the triploid endosperm is double that of
the embryo.
One primitive species of flowering plant, Nuphar polysepala,
has endosperm that is diploid, resulting from the fusion of a sperm
with one, rather than two, maternal nuclei. It is believed that early in
the development of angiosperm linages, there was a duplication in this
mode of reproduction, producing seven-celled/eight-nucleate female
gametophytes, and triploid endosperms with a 2:1 maternal to paternal
genome ratio.
In many plants, the development of the flesh of the fruit is
proportional to the percentage of fertilised ovules. For example, with watermelon,
about a thousand grains of pollen must be delivered and spread evenly
on the three lobes of the stigma to make a normal sized and shaped
fruit.
Cross-fertilisation and self-fertilisation represent different
strategies with differing benefits and costs. An estimated 48.7% of
plant species are either dioecious or self-incompatible obligate
out-crossers. It is also estimated that about 42% of flowering plants exhibit a mixed mating system in nature.
In the most common kind of mixed mating system, individual plants
produce a single type of flower and fruits may contain self-fertilised,
out-crossed or a mixture of progeny types. The transition from
cross-fertilisation to self-fertilisation is the most common
evolutionary transition in plants, and has occurred repeatedly in many
independent lineages. About 10-15% of flowering plants are predominantly self-fertilising.
Self-Pollination
Under circumstances where pollinators and/or mates are rare, self-fertilisation offers the advantage of reproductive assurance.
Self-fertilisation can therefore result in improved colonisation
ability. In some species, self-fertilisation has persisted over many
generations. Capsella rubella is a self-fertilisating species that became self-compatible 50,000 to 100,000 years ago. Arabidopsis thaliana is a predominantly self-fertilising plant with an out-crossing rate in the wild of less than 0.3%; a study suggested that self-fertilisation evolved roughly a million years ago or more in A. thaliana. In long-established self-fertilising plants, the masking of deleterious mutations
and the production of genetic variability is infrequent and thus
unlikely to provide a sufficient benefit over many generations to
maintain the meiotic apparatus. Consequently, one might expect
self-fertilisation to be replaced in nature by an ameiotic asexual form
of reproduction that would be less costly. However the actual
persistence of meiosis and self-fertilisation as a form of reproduction
in long-established self-fertilising plants may be related to the
immediate benefit of efficient recombinational repair of DNA damage during formation of germ cells provided by meiosis at each generation.
Fertilisation in animals
The mechanics behind fertilisation has been studied extensively in
sea urchins and mice. This research addresses the question of how the sperm
and the appropriate egg find each other and the question of how only
one sperm gets into the egg and delivers its contents. There are three
steps to fertilisation that ensure species-specificity:
Chemotaxis
Sperm activation/acrosomal reaction
Sperm/egg adhesion
Internal vs. external
Consideration as to whether an animal (more specifically a vertebrate) uses internal or external fertilisation is often dependent on the method of birth. Oviparous animals laying eggs with thick calcium shells, such as chickens,
or thick leathery shells generally reproduce via internal fertilisation
so that the sperm fertilises the egg without having to pass through the
thick, protective, tertiary layer of the egg. Ovoviviparous and viviparous animals also use internal fertilisation. It is important to note that although some organisms reproduce via amplexus,
they may still use internal fertilisation, as with some salamanders.
Advantages to internal fertilisation include: minimal waste of gametes;
greater chance of individual egg fertilisation, relatively "longer" time
period of egg protection, and selective fertilisation; many females
have the ability to store sperm for extended periods of time and can
fertilise their eggs at their own desire.
Oviparous animals producing eggs with thin tertiary membranes or
no membranes at all, on the other hand, use external fertilisation
methods. Advantages to external fertilisation include: minimal contact
and transmission of bodily fluids; decreasing the risk of disease
transmission, and greater genetic variation (especially during broadcast
spawning external fertilisation methods).
Sea urchins
Acrosome reaction on a sea urchin cell.
Sperm find the eggs via chemotaxis, a type of ligand/receptor interaction. Resact is a 14 amino acid peptide purified from the jelly coat of A. punctulata that attracts the migration of sperm.
After finding the egg, the sperm penetrates the jelly coat
through a process called sperm activation. In another ligand/receptor
interaction, an oligosaccharide component of the egg binds and activates
a receptor on the sperm and causes the acrosomal reaction.
The acrosomal vesicles of the sperm fuse with the plasma membrane and
are released. In this process, molecules bound to the acrosomal vesicle
membrane, such as bindin, are exposed on the surface of the sperm.
These contents digest the jelly coat and eventually the vitelline
membrane. In addition to the release of acrosomal vesicles, there is
explosive polymerisation of actin to form a thin spike at the head of the sperm called the acrosomal process.
The sperm binds to the egg through another ligand reaction between receptors on the vitelline membrane. The sperm surface protein bindin, binds to a receptor on the vitelline membrane identified as EBR1.
Fusion of the plasma membranes of the sperm and egg are likely
mediated by bindin. At the site of contact, fusion causes the formation
of a fertilisation cone.
Mammals
Mammals internally fertilise through copulation. After a male ejaculates, many sperm move to the upper vagina (via contractions from the vagina) through the cervix and across the length of the uterus to meet the ovum. In cases where fertilisation occurs, the female usually ovulates
during a period that extends from hours before copulation to a few days
after; therefore, in most mammals it is more common for ejaculation to
precede ovulation than vice versa.
The capacitated spermatozoon and the oocyte meet and interact in the ampulla of the fallopian tube.
Rheotaxis, thermotaixs and chemotaxis are known mechanisms in guiding
sperm towards the egg during the final stage of sperm migration. Spermatozoa respond to the temperature gradient of ~2 °C between the oviduct and the ampulla, and chemotactic gradients of progesterone have been confirmed as the signal emanating from the cumulus oophorus cells surrounding rabbit and human oocytes.
Capacitated and hyperactivated sperm respond to these gradients by
changing their behaviour and moving towards the cumulus-oocyte complex.
Other chemotactic signals such as formyl Met-Leu-Phe (fMLF) may also
guide spermatozoa.
The zona pellucida,
a thick layer of extracellular matrix that surrounds the egg and is
similar to the role of the vitelline membrane in sea urchins, binds with
the sperm. Unlike sea urchins, the sperm binds to the egg before the
acrosomal reaction. ZP3, a glycoprotein in the zona pellucida, is responsible for egg/sperm adhesion in mice. The receptor galactosyltransferase
(GalT) binds to the N-acetylglucosamine residues on the ZP3 and is
important for binding with the sperm and activating the acrosome
reaction. ZP3 is sufficient though unnecessary for sperm/egg binding.
Two additional sperm receptors exist: a 250kD protein that binds to an
oviduct secreted protein, and SED1, which independently binds to the
zona. After the acrosome reaction, the sperm is believed to remain
bound to the zona pellucida through exposed ZP2 receptors. These
receptors are unknown in mice but have been identified in guinea pigs.
In mammals, the binding of the spermatozoon to the GalT initiates the acrosome reaction. This process releases the hyaluronidase that digests the matrix of hyaluronic acid in the vestments around the oocyte. Fusion between the oocyte plasma membranes and sperm follows and allows the sperm nucleus, the typical centriole, and atypical centriole that is attached to the flagellum, but not the mitochondria, to enter the oocyte. The protein CD9 likely mediates this fusion in mice (the binding homolog). The egg "activates" itself upon fusing with a single sperm cell and thereby changes its cell membrane to prevent fusion with other sperm. Zinc atoms are released during this activation.
This process ultimately leads to the formation of a diploid cell called a zygote. The zygote divides to form a blastocyst and, upon entering the uterus, implants in the endometrium, beginning pregnancy. Embryonic implantation not in the uterine wall results in an ectopic pregnancy that can kill the mother.
In such animals as rabbits, coitus induces ovulation by stimulating the
release of the pituitary hormone gonadotropin; this release greatly
increases the likelihood of pregnancy.
Humans
Fertilisation
in humans. The sperm and ovum unite through fertilisation, creating a
zygote that (over the course of 8-9 days) implants in the uterine wall,
where it resides for nine months.
The term conception commonly refers to fertilisation, which is
the successful fusion of gametes to form a new organism. Its use
'conception' by some to refer to implantation makes it a subject of semantic arguments about the beginning of pregnancy, typically in the context of the abortion debate.
Upon gastrulation,
which occurs around 16 days after fertilisation, the implanted
blastocyst develops three germ layers, the endoderm, the ectoderm and
the mesoderm, and the genetic code of the father becomes fully involved
in the development of the embryo; later twinning is impossible.
Additionally, interspecies hybrids survive only until gastrulation and
cannot further develop.
However, some human developmental biology literature refers to the conceptus
and such medical literature refers to the "products of conception" as
the post-implantation embryo and its surrounding membranes. The term "conception" is not usually used in scientific literature because of its variable definition and connotation.
Insects
Red-veined darters (Sympetrum fonscolombii)
flying "in cop" (male ahead), enabling the male to prevent other males
from mating. The eggs are fertilised as they are laid, one at a time.
Insects in different groups, including the Odonata (dragonflies and damselflies) and the Hymenoptera (ants, bees, and wasps)
practise delayed fertilisation. Anong the Odonata, females may mate
with multiple males, and store sperm until the eggs are laid. The male
may hover above the female during egg-laying (oviposition) to prevent
her from mating with other males and replacing his sperm; in some groups
such as the darters, the male continues to grasp the female with his
claspers during egg-laying, the pair flying around in tandem. Among social Hymenoptera, honeybee queens mate only on mating flights, in a short period lasting some days; a queen may mate with eight or more drones. She then stores the sperm for the rest of her life, perhaps for five years or more.
Fertilisation in fungi
In many fungi (except chytrids), as in some protists, fertilisation is a two step process. First, the cytoplasms of the two gamete cells fuse (called plasmogamy), producing a dikaryotic or heterokaryotic cell with multiple nuclei. This cell may then divide to produce dikaryotic or heterokaryotic hyphae. The second step of fertilisation is karyogamy, the fusion of the nuclei to form a diploid zygote.
In chytrid fungi, fertilisation occurs in a single step with the fusion of gametes, as in animals and plants.
Fertilisation in protists
Fertilisation in protozoa
There are three types of fertilisation processes in protozoa:
gametogamy;
autogamy;
gamontogamy.
Fertilisation and genetic recombination
Meiosis
results in a random segregation of the genes that each parent
contributes. Each parent organism is usually identical save for a
fraction of their genes; each gamete is therefore genetically unique. At fertilisation, parental chromosomes combine. In humans, (2²²)² = 17.6x1012 chromosomally different zygotes are possible for the non-sex chromosomes, even assuming no chromosomal crossover. If crossover occurs once, then on average (4²²)² = 309x1024
genetically different zygotes are possible for every couple, not
considering that crossover events can take place at most points along
each chromosome. The X and Y chromosomes undergo no crossover events and are therefore excluded from the calculation. The mitochondrial DNA is only inherited from the maternal parent.
Parthenogenesis
Organisms that normally reproduce sexually can also reproduce via parthenogenesis,
wherein an unfertilised female gamete produces viable offspring. These
offspring may be clones of the mother, or in some cases genetically
differ from her but inherit only part of her DNA. Parthenogenesis occurs
in many plants and animals and may be induced in others through a
chemical or electrical stimulus to the egg cell. In 2004, Japanese
researchers led by Tomohiro Kono succeeded after 457 attempts to merge the ova
of two mice by blocking certain proteins that would normally prevent
the possibility; the resulting embryo normally developed into a mouse.
Allogamy and autogamy
Allogamy,
which is also known as cross-fertilisation, refers to the fertilisation
of an egg cell from one individual with the male gamete of another.
Autogamy which is also known as self-fertilisation, occurs in
such hermaphroditic organisms as plants and flatworms; therein, two
gametes from one individual fuse.
Other variants of bisexual reproduction
Some relatively unusual forms of reproduction are:
Gynogenesis: A sperm stimulates the egg to develop without fertilisation or syngamy. The sperm may enter the egg.
Hybridogenesis: One genome is eliminated to produce haploid eggs.
Canina meiosis:
(sometimes called "permanent odd polyploidy") one genome is transmitted
in the Mendelian fashion, others are transmitted clonally.
“It has been shown in the present volume that the
offspring from the union of two distinct individuals, especially if
their progenitors have been subjected to very different conditions, have
an immense advantage in height, weight, constitutional vigour and
fertility over the self-fertilised offspring from one of the same
parents. And this fact is amply sufficient to account for the
development of the sexual elements, that is, for the genesis of the two
sexes.”
In addition, it is thought by some,
that a long-term advantage of out-crossing in nature is increased
genetic variability that promotes adaptation and/or avoidance of
extinction.
Summary: Researchers say we constantly create false memories to help us achieve the identity we want.
Source: The Conversation
We
all want other people to “get us” and appreciate us for who we really
are. In striving to achieve such relationships, we typically assume that
there is a “real me”. But how do we actually know who we are? It may
seem simple – we are a product of our life experiences, which we can be
easily accessed through our memories of the past.
Indeed, substantial research has shown
that memories shape a person’s identity. People with profound forms of
amnesia typically also lose their identity – as beautifully described by
the late writer and neurologist Oliver Sacks in his case study of
49-year-old Jimmy G, the “lost mariner”, who struggles to find meaning
as he cannot remember anything that’s happened after his late
adolescence.
But it turns out that identity is often not a
truthful representation of who we are anyway – even if we have an intact
memory. Research shows that we don’t actually access and use all
available memories when creating personal narratives. It is becoming
increasingly clear that, at any given moment, we unawarely tend to
choose and pick what to remember.
When we create personal
narratives, we rely on a psychological screening mechanism, dubbed the
monitoring system, which labels certain mental concepts as memories, but
not others. Concepts that are rather vivid and rich in detail and
emotion – episodes we can re-experience – are more likely to be marked
as memories. These then pass a “plausibility test” carried out by a
similar monitoring system which tells whether the events fit within the
general personal history. For example, if we remember flying unaided in
vivid detail, we know straight away that it cannot be real.
But
what is selected as a personal memory also needs to fit the current idea
that we have of ourselves. Let’s suppose you have always been a very
kind person, but after a very distressing experience you have developed a
strong aggressive trait that now suits you. Not only has your behaviour
changed, your personal narrative has too. If you are now asked to
describe yourself, you might include past events previously omitted from
your narrative – for example, instances in which you acted
aggressively. False memories
And this is
only half of the story. The other half has to do with the truthfulness
of the memories that each time are chosen and picked to become part of
the personal narrative. Even when we correctly rely on our memories,
they can be highly inaccurate or outright false: we often make up
memories of events that never happened.
Remembering is not like
playing a video from the past in your mind – it is a highly
reconstructive process that depends on knowledge, self image, needs and
goals. Indeed, brain imaging studies have shown that
personal memory does not have just one location in the brain, it is
based on an “autobiographical memory brain network” which comprises many
separate areas.
A crucial area is the frontal lobes, which are in
charge of integrating all the information received into an event that
needs to be meaningful – both in the sense of lacking impossible,
incongruent elements within it, but also in the sense of fitting the
idea the individual remembering has of themselves. If not congruent or
meaningful, the memory is either discarded or undergoes changes, with
information added or deleted.
Memories are therefore very malleable, they can be distorted and changed easily, as many studies in
our lab have shown. For example, we have found that suggestions and
imagination can create memories that are very detailed and emotional
while still completely false.
Jean Piaget, a famous developmental psychologist, remembered all his
life in vivid detail an event in which he was abducted with his nanny –
she often told him about it. After many years, she confessed to having
made the story up. At that point, Piaget stopped believing in the
memory, but it nevertheless remained as vivid as it was before.
Memory manipulation
We
have assessed the frequency and nature of these false and
no-longer-believed memories in a series of studies. Examining a very
large sample across several countries, we discovered that they are
actually rather common. What’s more, as for Piaget, they all feel very much like real memories.
Many
parts of the brain are involved in creating personal
memories.
NeuroscienceNews.com image is adapted from The
Conversation news
release.
This remained true
even when we successfully created false memories in the lab using
doctored videos suggesting that participants had performed certain
actions. We later told them that these memories never actually happened.
At this point, the participants stopped believing in the memory but
reported that the characteristics of it made them feel as if it were
true.
A common source of false memories are photos from the past. In a new study, we have discovered
that we are particularly likely to create false memories when we see an
image of someone who is just about to perform an action. That’s because
such scenes trigger our minds to imagine the action being carried out
over time.
But is all this a bad thing? For a number of years,
researchers have focused on the negatives of this process. For example,
there are fears that therapy could create false memories of historical
sexual abuse, leading to false accusations. There have also been heated
discussions about how people who suffer from mental health problems –
for example, depression – can be biased to remember
very negative events. Some self-help books therefore make suggestions
about how to obtain a more accurate sense of self. For example, we could
reflect on our biases and get feedback from others. But it is important
to remember that other people may have false memories about us, too.
Crucially,
there are upsides to our malleable memory. Picking and choosing
memories is actually the norm, guided by self-enhancing biases that lead
us to rewrite our past so it resembles what we feel and believe now.
Inaccurate memories and narratives are necessary, resulting from the
need to maintain a positive, up-to-date sense of self.
My own
personal narrative is that I am a person who has always loved science,
who has lived in many countries and met many people. But I might have
made it up, at least in part. My current enjoyment for my job, and
frequent travels, might taint my memories. Ultimately, there may have
been times when I didn’t love science and wanted to settle down
permanently. But clearly it doesn’t matter, does it? What matters is
that I am happy and know what I want now.
About this neuroscience research article
Funding: Giuliana Mazzoni receives funding from ESRC, British Academy, Canadian SSHRC, Leverhulme Trust, Wellcome Trust.
Source: Giuliana Mazzoni – The Conversation Publisher: Organized by NeuroscienceNews.com. Image Source: NeuroscienceNews.com image is adapted from The Conversation news release.
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