Embryology Biology 441 Spring 2013 Albert Harris


Sex Determination

The mechanisms that control whether a given animal will develop into a male or develop into a female, or in some kinds of animal into a hermaphrodite

In humans and other mammals, development into a male is caused by one specific gene right at the end of the Y chromosome.

This gene has been cloned, sequenced and named SRY in humans (the equivalent gene in mice has also been found)

The proteins coded for by these genes are believed to be transcription factors (proteins that bind to DNA and control transcription of other genes).

A certain autosomal gene has also been found that is needed for male development, and its transcription is (probably) controlled by the SRY protein.

Normal males have one X chromosome and one Y chromosome, in addition to two each of all the other 22 kinds of chromosome (which are called the "autosomes", as compared with the X and Y, which are "sex chromosomes").

Normal female mammals have two X chromosomes, along with 2 of all the autosomes. But mammals will develop as males if they have two X chromosomes, and also a Y chromosome.

Sometimes the DNA of that one, male-determining gene breaks loose and gets attached to an X chromosome (which is an example of a chromosome translocation).
Individuals (whether mice or humans) with two X chromosomes will develop into a male if either of their X chromosomes has that special gene translocated to it.

Each (normal) sperm cell contains a complete set of autosomes, plus either one X chromosome or one Y chromosome. All normal egg cells (in mammals) contain a set of autosomes and an X chromosome. If an egg cell gets fertilized by one of the Y containing sperm, then that embryo will develop into a male. Conversely, females develop from eggs that got fertilized by one of the X containing sperm.

Half the sperm contain X chromosomes and the other half contain Y chromosomes, so you would expect the the sex ratio to be exactly 50-50. But that ratio depends on the two kinds of sperm having equal probabilities of "success" in reaching the upper end of the Fallopian tubules and fertilizing an egg. The actual human sex ratio is slightly different: more like 51% to 49%, with a percent or so more males being born. This could result from the "male" sperm swimming faster, or any number of small differences. The death rate for male humans is significantly higher, from before birth onward.

Evolutionary biologists argue that selection should tend to make our sex ratios 50-50 at the ages when reproduction occurs; from which it follows that higher death rates in males would tend to cause evolution of mechanisms to distort the sex ratio at birth in favor of males.

Many couples wish they could chose the sex of their next child, sometimes even to the extent of using ultrasound or tissue fragments to determine if a developing fetus is male or female, and then aborting those of whichever sex they don't want.

It would be far better if methods could be invented for mass separation of sperm cells (for example, by methods analogous to centrifugation, or electrophoresis) according to whether they contain an X or a Y chromosome, and then carry out artificial insemination with just X-containing or just the Y-containing sperm. Such methods have been reported again and again, and the most recent reports may finally be valid. I mention this subject as an example of one of the many ways in which the basic facts learned in this course might be put to medical or other uses.

A more depressing fact is that several common pollutants tend to convert developing males into (abnormal!) females, at least in many animals. Such chemicals include PCBs and "atrazine" which is the most heavily used herbicide in the world. They may also reduce the fertility of human males. Not nearly enough is being done either to reduce these dangers or to continue research about them. In those famous words from "Mad Magazine": What, me worry?

Steroid sex hormones are also part of the control of how the embryonic body develops. In many species, the morphology of a developing embryo can be forced to develop into the opposite sex, by injecting large enough quantities of steroid sex hormones. But they may not be anatomically normal in the development of their gonads and sex ducts.

Similarly, a certain genetic abnormality occurs in some human males, who have mutations in the genes that code for the receptor proteins that bind to male sex hormones. The cells of their bodies are therefore unable to detect the male steroid sex hormones being secreted by their testes, but their cells can detect the smaller amounts of female steroid sex hormones that are produced in both sexes. So these male humans look like women, externally, and usually grow up thinking they are women. But they have testes where their ovaries should be; and their sex ducts are also male-like. This is called androgen insensitivity syndrome.

Other genetic abnormalities have been found which convert genetic females into anatomical "males". There is much more research on this subject than we have time to cover in this course. Scott Gilbert's "Developmental Biology" textbook (7th edition) is a good source for more on this topic, as well as citations to the original research papers. He also has a page and a half about possible anatomical and genetic causes of sexual "preference".

The sex of birds is also determined by special sex chromosomes. However, in birds the female is the sex that gets one copy of a special chromosome, and the male is the sex whose cells each have two copies of their other kind of sex chromosomes. Sometimes these are called W and Z chromosomes.

In some fish, multiple sex chromosomes have been reported (with more than two kinds), and many other kinds of (teleost) fish regularly switch sexes. Some are males when younger, and then turn into females as they get older. These are genuine sex changes, with production of sperm during the male stage of life and production of egg cells during the female stage. These include several of the species most commonly caught by fishermen along the N.C. coast. Little do they know!

In other species of fish, they are females first, and then turn into males, in some cases in direct response to the absence of males in their vicinity. If the local male gets caught by a fisherman, or something, then a female will change into a male. Nobody could invent such stuff, so it must be true.

Not all animals use chromosomes, or even genes, to decide which sex their embryos will develop into. A surprising example, discovered not that many years ago, is that turtle sex is controlled by the temperature at which each egg is incubated at some certain stage of embryonic development. For examples, among local species, Painted Turtles and Box Turtles develop as males from cooler eggs, and as females when the eggs are incubated above some threshold temperature. All turtles bury their eggs in holes that they dig with their hind legs, and laying in shady areas will result in 100% male baby turtles. In contrast, Mud and Musk Turtles have a different system of temperature control of sex, in that there is a middle range of temperatures that produces mostly males, while either lower or higher temperatures result in higher percentages of females. Some other kinds of turtles apparently don't use temperature at all, and it isn't known what sort of mechanism is used instead. Alligator eggs follow a similar pattern to that just described for Musk Turtles.

Sex determination in flies (Drosophila) seems superficially to be the same as in mammals in that females have two X chromosomes, and males have one X and one Y chromosome.

At a more fundamental level, however, the systems are very different.

For one thing, the ratio of X chromosomes to autosomes is the key controlling variable in flies, not the presence of absence of a Y chromosome.

A Y chromosome is needed for males to develop normally, but a fly that has one X chromosome per cell, and no Y will develop into a (sterile) male. In mammals, such an XO individual would develop as a (probably sterile) female.

It's the low number of X chromosomes, relative to the two sets of autosomes, that controls sex in flies. Loyal tar heel students may be happy to know that three of the most important scientists who worked out the molecular mechanisms of sex determination in flies were professors in this department (i.e. UNC Biology). John Lucchesi, Gustavo Maroni and Bruce Baker.

There are (at least!) two other important differences in sex determination in flies, as compared with mammals. One is that each individual cell's morphological sex is controlled by the genes in that cell.

This is instead of having sex hormones, or anything equivalent to them, that stimulate sex changes all over the body. This is also true of other kinds of insects. Part of a fly can develop like one sex, and the rest like the opposite sex. Cells that have two X chromosomes will have shapes and/or colors normally only found in females, while if the cells next to them have only one Y chromosome, then these adjacent cells will have the shape and other properties of male cells. The name gynandromorph refers to sexual mosaic individuals like this, and some butterfly collectors prize them greatly. In principle, I suppose something like this could happen in a human if the genes for the receptors of the male sex hormone became mutated during embryonic development, so that some of the person's cells had the receptors and other cells did not. But I have never heard of such a case.

The taxonomic group of insects called Hymenoptera control sex in yet a different way: fertilized eggs develop into females (with two sets of chromosomes = "diploid"), and eggs that are not fertilized (and are therefore haploid ) develop into males .

Among other consequences, this results in sisters inheriting 75% the same genes, instead of 50% as in human siblings. It had long been a puzzle why three of the four groups of "social insects" are hymenoptera (i.e. ants, wasps and bees, and NOT termites which belong to a different group).

Scientists tried to think of reasons why the business of living in colonies, having a "Queen", and all that, should have evolved so often in this one particular group of insects.

When I was a senior in college, I wrote a term paper about this issue, and invented some theories of my own. That was the same year that W. D. Hamilton became famous by inventing what is certain to be the true explanation, which is that evolution of altruistic behaviors is favored in proportion to what fraction of genes are "shared" among populations. This insight stimulated the creation of what is nearly a whole new branch of biology, called "Sociobiology", which looks for patterns in the evolution of instinctive behaviors of animal interaction.

In many scientists, this stimulated the single most intense feeling of "Ohmygoodnesswhydidn'tIthinkofthat-ness!" that many of us have ever had in our lives. [MeinGottwarumhätteIchdasnichtgedachtheit, is the technical German term]


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