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Two’s Company, Three’s a crowd:
The Evolution of Two Sexes

By Claire Asher, on 6 May 2014

You’ve probably never given much consideration to why there are men and women. Or, more specifically, why there are two sexes, rather than one, three or 50. But this is a question that has been keeping some scientists awake at night for decades. Recent research in the department of Genetics, Evolution and Environment used mathematical models of evolution to investigate how the evolution of the two sexes was influenced by the inheritance patterns of the energy-producing organelle, mitochondria. The results of this model contradict previous work supporting the idea that inheritance of mitochondria through only one parent might explain the emergence of two sexes. The evolutionary dynamics of mitochondrial inheritance are more complex than previously thought.

Sexual reproduction is a beneficial thing, in evolutionary terms, but this benefit doesn’t depend upon there being different sexes, only on there being two individuals sharing their genes to produce an offspring. This system would also work with no sexes at all (everyone can mate with everyone), or with many sexes. In fact, two is actually the worst number you could have picked – with two sexes any individual is limited to an available pool of mates just 50% of the population. With three sexes, this pool would increase to 66% of the population, with four 75%, and so on. So why have most sexually-reproducing species on settled on two sexes?

In a few previous GEE blog articles (see here and here), I have discussed the phenomenon known as ‘uniparental mitochondrial inheritance’ (UPI), in which mitochondria, organelles found in our cells that are responsible for generating energy, are inherited only through the maternal line – that is, you inherit all of your mitochondria from your mother and none from your father. UPI is found in many living things, although some species do things a bit differently and there are many different ways to achieve the same result. Work by GEE researcher Professor John Allen has previously shown that the mitochondria within egg cells in jellyfish, fruit flies and fish are largely inactive; this inactivity allows for a perfect ‘mitochondrial template’ to be passed on to the offspring and prevent the accumulation of mutations through the generations. Essentially, this is why aging isn’t heritable. It wouldn’t work to inactivate sperm mitochondria because they need so much energy for all that swimming, so if we did inherit mitochondria from our fathers they would probably be mutated. UPI is also thought to help evolution remove harmful mutations from the population and reduce conflict and promote coadpatation between the mitochondrial symbiont and its host cell.

Fertilisation So, UPI makes a lot of sense, evolutionarily, and some scientists think it might also explain why we have two sexes, as opposed to any other mating system. It’s important to be clear, when we talk about having two sexes we’re saying nothing about the external differences between the sexes (sexual dimorphism) observed in many multicellular organisms. We’re talking about the existence of two ‘mating types’, such that individuals cannot mate with members of the same type. Recent research by another group of GEE academics including Professor Andrew Pomiankowski, Dr Nick Lane and Professor Robert Seymour, investigated the evolution of UPI and in particular it’s relationship with the evolution of a two-sex mating system. We might expect a strong link between UPI and the existence of two sexes, since uniparental inheritance immediately generates differences between the two mating partners, and ensures that reproduction is not possible unless one member of each ‘type’ is present. Although UPI is often thought to have been a key driver in the evolution of mating types, there have been few investigations of what conditions are needed for the fitness benefits of UPI to actively drive the emergence of two mating types. So the authors developed a new mathematical model of mitochondrial inheritance and the evolution of UPI in a population where biparental inheritance (BPI) is the norm. They incorporated mitochondrial mutation (which might sometimes be selfish) and selection into the model, and included different mating types.

The model agreed with a great deal of previous work that indicates that UPI tends to increase fitness. It does so slowly, with selection acting cumulatively across many generations to remove less fit mitochondrial variants and increase fitness for UPI individuals. In a population of individuals where mitochondria is inherited biparentally, a new mutation causing UPI exists in a single individual. Slowly UPI improves the fitness of cells by reducing the number of mutated mitochondria they carry, and the UPI mutation might start to spread in the population. The problem is, as it spreads the benefits of UPI are inevitably leaked into the rest of the BPI population – UPI individuals mate with BPI individuals producing some BPI offspring who carry the fitter mitochondria from their UPI parent. This leaking of benefits means that the fitness benefits of UPI are frequency-dependent; the more common UPI becomes in a population, the less each UPI individual benefits from the reproductive strategy. This makes it hard for UPI to fully take over a population – their model tended instead to produce mixed populations with some UPI and some BPI individuals interbreeding.

Mitochondrial Evolution - Leaking of beneficial mutatations

Leaking of fit mitochondrial (blue) into BPI cells (a)

If the researchers included mating types in the model at the start of it’s evolutionary run, then UPI could become associated with specific mating types and in this situation, so long as mutation rates were high or each cell carried many mitochondria, UPI could spread to fixation in the population. But UPI itself was not able to alter the number or existence of mating types. The authors suggest that this may explain the continuum of UPI levels we observe in nature. For any given species, the occurrence of UPI will depend upon the evolutionary starting point, energetic demands, mutation rates and the selfish (or unselfish) nature of mutations.

Although most people never even consider why we have two sexes, male and female, the evolution of a two mating-type system is seemingly paradoxical and many theories and hypotheses have been proposed to explain it. One such explanation is that uniparental inheritance, which is critical for stabilising the mitochondria-cell symbiosis and preventing the accumulation of harmful mutations, may have driven the evolution of two sexes. However, mathematical modelling by scientists in GEE suggests this is not the case, and UPI more likely evolved after the two mating-type system emerged. In their model, although UPI initially spreads through populations, it’s fitness benefits are frequency-dependent, meaning it only rarely takes over an entire population. Populations in which all members inherit mitochondrial uniparentally are only possible when a mutation causing UPI becomes tighly linked to genes that determine mating type. The initial emergence of two mating types still requires an explanation independent from mitochondrial inheritance patterns.

Original Article:

() Proceedings of the Royal Society B: Biological Sciences

This research was made possible by funding from the Natural Environment Research Council (NERC), the Engineering and Physical Sciences Research Council (EPSRC) and the Leverhulm Trust.

Damage and Fidelity: The Role of the Female Germline in mtDNA Inheritance

By Claire Asher, on 11 November 2013

Billions of years ago, one single-celled organism engulfed another, beginning a symbiotic interaction that would change live on Earth forever. The mitochondria are what remains of this symbiotic event, and are responsible for producing energy in all eukaryotic cells. Derived from a free-living organism, they carry their own genes, but these genes are at risk of damage by a natural by-product of energy production – free radicals. Mitochondrial DNA in most cells are exposed to these reactive oxygen species and may be damaged over time, resulting in some diseases of age. However, if damage occurs to the mitochondrial genes in egg and sperm cells, this damage would be passed on to the next generation. Despite this, aging is not heritable, and very few mitochondrial mutations are passed from one generation to the next. Researchers in GEE have been investigating the mechanism responsible for this apparent paradox – mitochondrial inactivation – and have discovered that this mechanism is extremely widespread in the animal kingdom.

The mitochondria are the powerhouses of the cell, generating energy through oxidative phosphorylation down an electron transport chain. The electron transport chain occurs across the mitochondrial membrane, and was a key innovation during the evolution of multicellular life. Mitochondria originated as free-living single celled organisms that were engulfed inside another cell and subsequently formed a cooperative partnership that allowed cells to produce energy more efficiently. Because of their symbiotic origin, mitochondria brought an entire genome with them, and although this has been wittled down to only a small number of genes, some genes still reside inside the mitochondria. This is a big problem, however, because in the process of producing energy, mitochondria also produce harmful reactive oxygen species (ROS), also known as free radicals. These can cause mutations in DNA, and the mitochondrial genes are therefore at great risk because of their proximity to the site of ROS production. Mutations in mitochondrial DNA are thought to be a key cause of age-related diseases.

The Electron Transport Chain
Image by Rozzychan, creative commons.

Mutations in DNA (mitochondrial or nuclear) in most cells in the body can be harmful to the health of the individual, but will have no influence on the next generation. The genes which we pass onto the next generation are separated off during early development into special ‘germ line’ cells which form sperm and eggs. Great care is taken to minimise the risk of mutation to these genes – genes in germline cells act as a blue print for the next generation. This is essentially why aging is not heritable, and it is a system that works pretty well.

Sperm Cells
Image by be_sperm

However, sperm and egg cells need mitochondria to produce energy, and so mitochondrial genes in our germ cells may still be at risk of mutation. If the free radicals generated in germ-line mitochondria harm mitochondrial DNA, these damages would be passed on to the next generation! Research in GEE has uncovered a rather elegant solution to this problem – those mitochondria that will be passed to the next generation are maintained in an inactive state. It’s a bit like buying two toasters and keeping one in a cupboard, unused, to provide a template from which to build a new toaster when the old one breaks.

Mitochondria are only inherited through the maternal line – every mitochondria in your body came from your mother, and this is true for most animal species. The mitochondria in sperm are generally discarded at some point prior to fertilisation. So, in order to preserve the fidelity of mitochondrial DNA passed on to the next generation, we only need to ‘switch-off’ mitochondria in egg cells. This is great, since sperm really need their mitochondria to provide energy for all that swimming!

Egg Cell

Previous research by John Allen and colleagues in GEE indicated that mitochondria in egg cells of the moon jellyfish (Aurelia aurita) are inactive compared to mitochondria in sperm and somatic tissues. Recently, GEE’s Prof John Allen, along with Wilson de Paula (Queen Mary University of London) and colleagues have investigated this phenomenon further and discovered that this system of mitochondrial inactivation is widespread across the animal kingdom. Using qPCR, a technique for measuring and comparing expression patterns of specific genes, they found that in both fruit flies (Drosophila melanogaster) and zebrafish (Danio rerio) expression of three key respiratory genes (nad1, cob & cox1) is much lower in mitochondria in oocytes (egg cells) than in sperm and active muscle tissue. Expression levels were 15-fold lower in eggs, whereas sperm and muscle showed similar levels of expression. They also found that membrane electrical potential, a measure of the activity of the electron transport chain, was reduced in oocytes compared to both sperm and the surrounding tissue. Further, ROS production was 50- and 100-fold lower in the eggs of fruit flies and zebrafish respectively. Finally, they confirmed that oocyte mitochodria in both species exhibit a simpler structure, indicative of reduced activity. So, it seems that in both fish and flies, the mitochondria in egg cells represent little more than a blueprint, ready to be passed on to the next generation error-free. By deactivating ovarian mitochondria, the fidelity of information is ensured across generations, and aging is not heritable.

Wilson de Paula and Prof John Allen have now identified a similar pattern of mitochondrial inactivation in species across the animal kingdom, including jellyfish, fruitflies and zebrafish. Early in multicellular evolution, animals branched into two key groups distinguished by differing patterns of embryonic development; protostomes (including arthropods, molluscs and nematodes) develop their mouth first, whereas deuterostomes (including vertebrates, tunicates and starfish) develop their anus first. This seemingly small difference represents a fundamental divide in the animal kingdom. This study therefore demonstrates that mitochondrial inactivation occurs in both of these key branches. Previous work by de Paula and Allen has shown a similar pattern in jellyfish, members of the phylum Cnidaria which pre-date the great protostome-deuterstome divide. Together, this work suggests that mitochondrial inactivation, as a mechanism to ensure fidelity of mitochondrial DNA transmission across generations, is likely to have emerged early in the evolution of multicellular life on Earth.

Ensuring the faithful transmission of genes to the next generation is a key problem for all life on Earth. Although the mitochondrial symbiosis event which marked the emergence of eukaryotic life was a major breakthrough in efficient cellular energy production, it brought problems of its own. Mitochondria must carry a few genes in order to maximise responsivness to cellular demands, but these genes are at risk of damage from a natural by-product of energy production – free radicals. A system of mitochondrial inactivation in female germ cells (eggs) may serve to resolve this conundrum, and seems to be shared across all animal life.

Original Article:

() Genome Biology and Evolution

This research was made possible by funding from the Natural Environment Research Council (NERC), and the The Leverhulme Trust

How Energy Shapes Life: Our Mitochondrial Partners

By Claire Asher, on 21 June 2013

Every cell in our bodies is a collaborative effort. A collaboration that dates back to just after the dawn of life itself, and marks one of the deepest divides in the tree of life. This symbiosis has had remarkably far-reaching effects, and is now thought to be key to understanding sex, ageing and death. The symbiotic entity in question is the mitochondrion; the power house of the cell. Biologists are increasingly realising the centrality of energy in understanding life, and a special issue of Philosophical Transactions of the Royal Society, introduced by Nick Lane, focuses on the synthesis of energy, genes and evolution.

Mitonucleus in Blue
Artwork by Odra Noel www.odranoel.eu
Image Used with Permission

Around 1.5 billion years ago, a simple, single-celled bacterium engulfed another one. But it didn’t eat it. Instead, the two cells started working together, and over the following millennia developed a cooperative relationship that laid the foundation for multicellular life and for diversification on a scale never seen before. This symbiotic relationship founded a new type of life – the eukaryote. Unlike their prokaryote ancestors, the eukaryotes had a special advantage: they now had internal membranes. This enabled them to generate energy more efficiently, utilising a force generated across a membrane, known as the proton-motive force. This allowed them to support bigger cells, a wider variety of diets, and ultimately led some eukaryotes to group together into multicellular, sexual organisms such as plants and animals.

Hand Over Your Genes!
Since mitochondria originated as free-living single celled organisms, they came complete with their own genetic information. As the cooperative partnership between the eukaryote host and its mitochondrial partners developed, the majority of these genes were transferred to the nuclear (host cell) genome. Bizarrely, though, a few genes remained with the mitochondria. In fact, the same few genes stayed put in almost all eukaryotes, even though this process happened many times independently. So what is so special about these genes? Why keep them in the mitochondria when it is costly to do so?

A Mitochondrion

A Rapid Response System
It is thought these genes remain in the mitochondria because they are needed there to allow individual mitochondria to respond rapidly to changes in the energy demands of the cell. When mitochondria are out-of-sync with their surroundings, they start generating dangerous ‘reactive oxygen species’ (ROS), also known as free radicals. Free radicals are famous for causing cancer, and this is because they act as mutagens, causing changes to DNA they encounter. Mutations caused by ROS can cause all sorts of problems, not just cancer, and many of the diseases of old age are thought to be caused by ROS mutations.

So, we need to keep a small set of genes – those that code for key components of the respiratory chain that generates energy in mitochondria – in close proximity to their site of use so that they can quickly respond to the ever-changing cellular environment. This is also true for chloroplasts in plants, and recent research by Puthiyaveetil and colleagues in GEE lends support for this explanation. They have found evidence for a chemical partnership, unique to eukaryotes, which may be important in regulating chloroplast function to minimise ROS production.

Both mitochondria and chloroplasts have held onto a few genes in order to allow a rapid response to changes in demand. Trouble is, by keeping those genes there, they are vulnerable to attack from any free radicals that are generated. Mutations in these genes can often cause the production of more free radicals, causing a downward spiral that eventually leads to the death of the cell.

Unusual Inheritance

Fertilisation

Mitochondrial genes are not inherited in the same way as normal nuclear genes. The majority of our genes (residing in the nucleus) are inherited biparentally, that is, we inherit half from our mother and half from our father. Mitochondrial genes, on the other hand, are inherited only in the maternal line, through the egg. Mitochondria are also present in sperm cells – they have to be, since they are crucial for providing energy to power all that intense swimming – but sperm mitochondria are killed shortly after fertilisation. Recent research by John Allen in GEE suggests that uniparental inheritance of mitochondrial genes relates back to those pesky free radicals.

In sperm cells, mitochondria are working overtime to make sure the sperm has the energy to swim and find the egg. In the process they are churning out free radicals, and damaging the mitochondrial DNA. The mitochondria inside sperm start to suffer from the ravages of old age. But we don’t want to pass on old mitochondria to our offspring. It seems evolution has found an elegant solution – switch off the mitochondria in egg cells and pass these young mitochondria on to your offspring. De Paula and colleagues looked at the mitochondria in eggs, sperm and the bell of moon jellyfish (Aurelia aurita) and found egg mitochondria were largely inactive and simple in structure. Egg mitochondria also showed reduced levels of gene expression, an almost non-existent membrane potential and produced no free radicals, indicating that they were not actively generating energy. Eggs don’t need that much energy compared to sperm, and they can borrow what they do need from other cells. By switching off the mitochondria in eggs, and making sure these are the only ones passed on to the next generation, eukaryotes can reduce the build-up of harmful age-related mutations in mitochondria from generation to generation.

The Moon Jellyfish (Aurelia aurita)

Energy, Mitochondria and the Meaning of Life
The generation of energy is central to life. Mitochondria generate energy in all eukaryotic cells (animals, plants, fungi), and the symbiotic event that brought them into the eukaryotic cell changed life on Earth forever. Mitochondria proved massively beneficial, allowing eukaryotes to try new things, and ultimately produce the huge diversity of multicellular life we see today. However, housing another genome inside the cell came with nuances of its own, which led us to have sex, to age and die. Recent research in GEE highlights one way in which evolution has overcome one of these nuances – by switching off mitochondria in egg cells, offspring can inherit an undamaged copy, and because of this, ageing is not heritable. Other research in plants is broadening our understanding of why these genes are stored inside the mitochondria and chloroplasts in the first place. Throughout a plethora of different disciplines, mitochondria are proving crucial to understanding the fundamentals of life.

Original Articles:

() Philosophical Transactions of the Royal Society B

() Philosophical Transactions of the Royal Society B

Introduction to the Special Issue:

() Philosophical Transactions of the Royal Society B

This research was made possible by funding from the Natural Environment Research Council (NERC) and the Leverhulme Trust