Sex determination

If yeast sex is simple, how complicated is sex in multicellular organisms? Actually, the act of sexual reproduction in plants and animals (including humans) is essentially identical to that of yeast, fungi, plants and animals, including humans. Multicellular organisms have two different copies of the genome in every cell. Like yeast, to undergo sex we need meiosis to occur. Specialised sexual cells duplicate the two genomes, cut and paste them into four unique genomes, and then divide into four daughter cells. These cells are either large cells containing a single genome and lots of energy (the female egg) or small cells containing nothing more than just a single genome (the male sperm). When they combine the new cell has two genomes, one from the female parent and one from the male parent. Importantly, just like yeast, the offspring that results has a unique genetic composition. The two genomes that the offspring possesses are each novel, created by the combination of the two unique genomes in each parent.

While sex for multicellular organisms is identical to yeast at the cellular level, at the sex determination level things get very complicated. There are many different ways for determining whether an individual is male or female. As a measure of the broad diversity of ways in which species have solved the sex determination problem we can look at a few different examples: clownfish, crocodiles, humans, whiptail lizards and komodo dragons. And this is not including some of the really complicated systems that exist, such as in earthworms, bees and platypi.

Clownfish and crocodiles

Clownfish and crocodiles both have non-genetic sex-determination systems. Males and females have the same genetic make-up and every genome has potential to encode either a male or female individual. The physical manifestations of sex occur due to environmental influences on which set of genetic controls to activate. In clownfish the important environmental influence is the social interaction of other clownfish. All clownfish start out as males. When the sole female in the group dies, the largest male undergoes a rapid sex change and becomes a female. Interestingly, this sex change is reversible – a female moved into a new group where she is no longer the largest will revert back to a male. This plasticity ensures that there is always a breeding female in every group, and that the female comes from the most successful individual in the group.

Like clownfish, crocodiles have no genetic difference between males and females. Unlike clownfish, however, there is no sex plasticity. A male hatches as a male and stays a male for life, a female hatches as a female and stays a female for life. The important environmental influence in this case is the temperature of the egg. If the temperature of the egg is between 31.7°C and 34.5°C the embryo is set as a male, if the temperature of the egg is outside this range the embryo is set as a female. There are several important restraints that this sex determination system has had on crocodile evolution. Firstly, the crocodilian mother has become very active in nest maintenance, as a temperate far from the threshold will result in hatchlings of a single sex. Secondly, this sex determination system has forced crocodiles to maintain a link to land. Other aquatic species, such as dolphins and sea snakes, have been able to become entirely aquatic by giving live birth in the water. These species all have genetic sex determination systems (below). By contrast, crocodiles and turtles need to return to land to lay eggs because a temperature-dependent sex determination system is incompatible with live birth – internal body temperatures are too stable to give the diversity in temperatures required.

Humans and whiptail lizards

Humans and whiptail lizards both use the XX/XY sex determination system. In this system, sex is determined by the combination of sex chromosomes inherited from the parents. XX results in females and XY results in males. As females can only pass on an X chromosome while males can pass on either an X (50% chance) or Y (50% chance) chromosome, this system results in roughly equal numbers of females and males being born. It is very important to note that differences between the sexes are largely not due to genetic differences. Both males and females have the X chromosome, and while females have two copies one of these copies is “inactivated”, making them equivalent to males. The only substantial genetic difference between males and females is the presence of the Y chromosome in males. This Y chromosome is tiny (only 2% of the human genome) and is mostly made of up junk. The only essential gene on the Y chromosome is the SRY gene.

All human embryos, whether XX or XY, spend the first six weeks as females. At this point embryos with the XY genome express the SRY gene in the genital tissue, starting the development of testes. The testes then express testosterone and the embryo detects this testosterone production through the androgen receptor. The effect of this production is a complete remodelling of the genitalia from female into male between 7 and 12 weeks gestation. Many different genes are used to initiate the “male” program instead of the “female” program, but only the SRY gene is on the Y chromosome. In other words, females have all the genes required to develop the physical attributes of a male, and males have all the genes required to develop the physical attributes of a female, and only a single gene decides which program is used. When thinking about physical differences between males and females it is not helpful to think about genetic variation, such as exists between different populations of humans. Instead the best comparison is to think about your heart and your liver. Both cells have the same genome, the same genetic code, but the two cells have initiated different programs from the same code so that the cells can perform different functions.

Most whiptail lizards use the same XX/XY system as humans, with XX lizards being female and XY lizards being male. However 15 species of whiptail lizards have reverted to an asexual system of reproduction. These species consist only of XX females. The females still undergo sexual meiosis to create an egg with a single X chromosome, however in the absence of sperm these eggs spontaneously duplicate their genome to become XX females, in a sexual system called parthenogenesis. It is unclear as to why these whiptail lizards have evolved to abandon the advantages to sexual reproduction, however a clue may be the environment they live in – the dry deserts of North America. It is likely that with the low population densities of lizards living in a desert finding a mate becomes very difficult. By breeding through parthenogenesis females can still reproduce even if they fail to find another lizard, and furthermore every individual offspring is capable of bearing young, allowing more efficient use of resources during dry times, and faster population growth during wet ones.

Komodo dragons

The ZW/ZZ sex determination system used by Komodo dragons is essentially the opposite of the XX/XY system. Here, ZW results in a female while ZZ results in a male. As with the Y chromosome, the W chromosome is a minor chromosome with few functions beyond sex determination. When breeding, a female Komodo dragon can pass on either a Z or W chromosome while a male Komodo dragon can only pass on a Z chromosome. This results in 50%:50% females to males. Interestingly, the Komodo dragon has also developed parthenogenesis, like the whiptail lizard. A female Komodo dragon kept alone will have spontaneous genome duplication of an egg. The outcome, however, is the opposite of that occurring in the whiptail lizard. The whiptail lizard female, using the XY sex determination system, can only pass on an X chromosome, so duplication results in an XX female. The female Komodo dragon, however, uses the ZW sex determination system, so the egg could either have a Z chromosome and duplication to be a ZZ male, or it could have a W chromosome and duplication to become an unviable WW embryo. In practise, therefore, this means that female Komodo dragons that revert to parthenogenesis will always generate ZZ males. This means that a lone female washed up on a new island will generate male offspring by parthenogenesis, allowing later sexual reproduction. What is the advantage of this system of parthenogenesis? There are two likely possibilities. The first is that it avoids the spiral into an inbred population that occurs in whiptail lizards, with only a single necessary parthenogenic generation interrupting sexual reproduction. This may be a more appropriate adaption to the “rich uninhabited island” scenario, with the XX parthenogenic strategy more suitable for the “low population desert” context. Alternatively, and equally plausible, the ZW parthogenesis strategy is less efficient than XX parthenogenesis in both contexts (or vice versa). Since evolution always works from the current genetic situation in incremental steps, non-ideal compromises are common.

The role of sex in evolution

Sex is a powerful force for evolution. On the face of it, sex seems like an absurdly complicated way to reproduce. Prokaryotic organisms, bacteria and archea, have a much faster a simpler system, where the cell simply duplicates its DNA and splits in half into two identical daughter cells. The entire process, called mitosis, only takes 20 minutes. This means that under ideal circumstances a single bacterium can divide to produce 8 offspring in the first hour. In the second hour that single precursor cell could form 64 offspring, after 6 hours a single cell could form over 200,000 daughter cells. This asexual reproduction is so efficient that it only operates at capacity for very short durations, as exponential growth of a single cell could use up the resources of an entire planet within days. Typically a bacterium ticks over slowly by scavenging what resources are available, only to explode into exponential asexual growth when new resources become available and a race to exploit them occurs.

Compare this to the elaborate, time-consuming and often bizarre process of eukaryotic sex, which multicellular organisms from plants to fungi to animals use to reproduce. Sex (and the accompanying mate selection) is one of the most difficult and dangerous parts of an individual’s life, and even passionate advocates of the activity find it difficult to explain. Yet through an evolutionary lens, sex provides very concrete advantages. The best illustration of the advantages of sex come from yeast mating, as these simple organisms are capable of both asexual and sexual reproduction.

Simple sex

Yeast can be thought of as being halfway between simple bacteria and complex multicellular organisms like humans. In terms of lifestyle and behaviour, yeast operate like bacteria – single celled organisms capable of an independent existence through the use of resources in their direct environment. Inside the cell, however, yeast are clearly eukaryotic organisms, with the same basic machinery for cell division, metabolism and survival as plants and animals. It is therefore convenient to think of yeast as essentially human-like cells, trapped in an early bacterial-like lifestyle. This is an oversimplification of course: bacteria, yeast and humans are all highly evolved organisms and none have remained static in evolutionary time, but it is a useful oversimplification.

So how do yeast reproduce? Asexually, like the bacteria they share a lifestyle with? Or sexually, like the multicellular organisms they are genetically closest to? The answer is both. When yeast are in a rich nutrient environment they reproduce asexually like bacteria. A single cell undergoes mitosis, duplicating its DNA and then splitting into two daughter cells, each identical to the parental cell. This gives the yeast all the advantages of bacterial reproduction – very simple rapid reproduction to win the race for abundant resources. The parental cell was successful in the environment, so the identical daughter cells should be equally successful and proliferate likewise.

However as noted above, exponential growth can never continue unabated, sooner rather than later resources become limiting or some other factor stresses the survival of the yeast. At this point yeast have a trick available that bacteria do not – sex. Instead of undergoing dormancy, the yeast mate.

In the best understood system, that of Saccharomyces cerevisiae, there are two sexes of yeast, a and a, controlled by a single gene. Mating is very simple, the a cells release a chemical called ‘a factor’ and produce a receptor that causes them to migrate towards the chemical ‘a factor’. By contrast, the a cells release a chemical called ‘a factor’ and produce a receptor that causes them to migrate towards the chemical ‘a factor’. The two yeast cells, one a and one a, attract each other and fuse into a single cell. This cell now has two different copies of the yeast genome, one from each parent.

The a-a fused yeast cell can now undergo a complicated cellular division process called meiosis. Unlike mitosis, where the cell duplicates its genome and divides in two, meiosis involves duplicating the genome and dividing in four. This is possible because the a-a fused yeast cell has two copies of the genome to start with, so duplication gives four copies, one for each of the four daughter cells that result.

The important difference between mitosis and meiosis is the splicing of two different genomes to form unique combinations. Mitosis just duplicates the existing genome. Meiosis starts with two different genomes, and during the duplication processes these genomes are jumbled up together, creating new combinations of old characteristics. This means that all four daughter cells at the end are unique and different from the original parental cells.

The advantage conferred by sex is very straight forward – the parental cells were not dealing well with the environment they were in, since yeast mating occurs only under stress. Therefore why reproduce more cells that cannot cope with the environment? Instead the yeast takes a life-or-death gamble that a combination of genetic information from another cell will produce offspring better able to deal with the environment. In a simple scenario there would be two yeast strains, one able to deal with acidity and one able to digest complex carbohydrates. A change in environment to a high acidity environment where the only resources available are complex carbohydrates will stress both parental strains. However, by sex there is a chance that one of the daughter cells will inherit the acid resistance of one parent and the ability to digest complex carbohydrates from the other parent. Other daughter cells will not be so lucky and will die, but that one daughter cell with the chance combination of two necessary characteristics will be able to divide asexually and rapidly reap the rewards of a new resource.

In one final complication, yeast can change sex. A single gene makes yeast either a or a, so after mating and meiosis the four daughter cells include two a cells and two a cells. If a single a cell is successful in the new environment, asexual reproduction creates exact copies, so all progeny will be a cells. This would create an obvious problem if a new environmental stress requires another round of mating, so yeast carry spare “silent” copies of a and a genes and use these backup copies to flip from one sex to another, to make sure a population is always a mixture of a and a yeast.