Wednesday, May 13, 2015

Half Male, Half Female, Completely Weird

Biology concepts – sex determination system, gynandromorphs, non-disjunction, mitosis, bilateral symmetry, chimera, mosaicism

Ardhanarishvara is just form of the god Shiva.
As a male, he is considered the ultimate man,
James Garner mixed with a little Steve McQueen.
Parvati, his wife, wanted to share his experiences,
so he became half her. That’s one
progressive marriage.
In the Hindu faith, Shiva is the destroyer. Anything that has a beginning must have and end, so as Brahma made the world Shiva must destroy it so that it can be remade. On a more positive note, Shiva is also the god of change, making people better versions of themselves by destroying the ego and bad habits.

Shiva is male and celibate, although he has a female consort named Parvati (aka. Shakti, Devi, or Uma). There is also a deity called Ardhanarishvara, which is a half male/half female representation of Shiva + Parvati. The icon is found in most temples to Shiva, but this deity rarely has temples dedicated to him/herself.

Evolution chose to go the other way with nature. In more complex animals, the sexes are separated and join energies to reproduce. In biological terms, it’s a matter of increasing genetic diversity, the source of mutations and drift for natural selection.

However, like Ardhanarishvara, nature sometimes gives us a mixture; a normally two sex species will produce an individual that is part male and part female. And sometimes they're exactly half and half. This is going to take some explaining.

Every once in a while, some embryos have a mistake in mitosis. When the chromosomes line up for random assortment and portioning into the daughter cells, things can go wrong. Once in a while, two chromatids (the two copies of a replicated chromosome) may get pulled into the same daughter cell instead pulled apart with one going to each daughter (called a non-disjunction event).

This produces one cell with too many copies of that chromosome, and one cell with too few. Both outcomes can cause problems. Sometimes, the problem is just cosmetic; sometimes it’s deadly.

Gene loss can come from losing a part of one
chromosome, or you might lose the whole
chromosome (monosomy). It could occur from a
non-disjunction or from some toxic event. A 2015
study shows that smoking can cause a loss of the Y
chromosome in some cells. This makes men more
at risk for some cancers due to smoking (those
outside the lung).  Still want a cigarette?
On the other hand, on very rare occasions a chromosome will be lost during mitosis (chromosome loss event). It ends up next to that sock you can’t find in the washer. Who knows where it is – it just ain’t where it ought to be. One daughter cell has the right number of chromosomes and the other has one too few. Again, the consequences can range from small to really big.

A third possibility exists, where a mutation occurs in one chromatid after replication, so that even if the mitosis is normal (which it almost always is) one daughter will have a mutation (one normal and one mutated gene on the two chromosomes of the same type) and the other won’t (two normal genes on two normal chromosomes).

From then on, every time the daughter cells divide they increase the number of mutated and normal cells. The animal, if it survives to be born, will be a chimera (a mixture of two genotypes). The original chimera was a Greek mythical figure made from the parts of many animals and which breathed fire. It was a half-brother to the Hydra and Cerberus, the three-headed dog. Here it means something less menacing, but just as interesting.

Special circumstances can bring special kinds of chimeras. Which type is formed depends on when the mutation, non-disjunction, or chromosome loss occurs. In some animals, the first cell division after fertilization establishes right and left halves of the animal. Every progeny cell from one of the first daughters will be one side of the body, while every cell coming from the other original daughter will be on the other half of the animal.

The lobster on the top is a mosaic, the mutation
which changed the pigment occurred at a point when
some mutated and some non-mutated cells were on
each bilateral half of the embryo, so there are patches
of each. The bottom version had a mutation that
occurred precisely as the embryo was determining
right and left sides.
If the chromosome change or gene mutation occurs at this point, then exactly one half of the animal will have the change and the other half won’t. This is a bilateral chimera. On the other hand, of the mutation/change occurs at some other point, the there will be patches of one type of cell and patches of the other. This is called a mosaic (see picture to the right).

A 2013 review talks about mutations in different populations of cells and the right left isolation of some mutations. The authors point out that in bilateral chimeras, it is easy to study subtle effects of the gene mutation – one half displays the mutation, and the other half doesn’t. A single animal (could be a person) can serve as the experimental model AND  the control.

For example, in fruit flies (Drosophila melanogaster) the males are XY and the females are XX. If there was chromosome loss early in development, with a single X lost in one daughter cell, there will be XX daughter cells and X (called X0) daughter cells. X0 cells are male because the primary sex determining is located on the X chromosome. In this case just described, the XX cells are female and the X0 cells are male, in the same animal!

This animal would be a gynandromorph chimera. The word is very telling, since gyno = female and andro = male. This is different from a hermaphrodite. The hermaphroditic animal has two sets of genitalia, one female and one male (whether they work or not is another question). In a gynandromorph, the two cell populations of the entire animal show different sex chromosomes.

The patterning on the thorax and abdomen is a bit
hard to see, but the eyes are easily picked out on the
gynandromorphic fruit fly. The pigment genes are
on the sex chromosome.
Gynandromorphs are extremely rare. In fact, they have been demonstrated in only two groups, but this is preliminary. Remember how we talked about animal sexual dimorphism a few weeks ago? Well, it’s only in sexual dimorphic animal species that you would actually notice gynandromorphs (of course, there are exceptions).  

Birds and arthropods are the two animal groups where we have seen gynandromorphs. We gave the example of fruit flies above. You can check out the picture of one to the left. This is specific example of gynandromorph, a bilateral gynandromorph. The left side is female and the right half is male.

In different systems of embryonic development, chimeras can develop side to side (bilateral), front to back (polar), or corner to corner (oblique). This is if the mutation or change in chromosome or gene number takes place at exactly the right mitotic event that divides an animal. If it is any of the other time, the animal will be a mosaic.

In the bilateral gynandromorphic fruit fly above, the color of the eyes is different on each side, as is the body coloring and some other characteristics. This is because the secondary sex characteristics that determine sexual dimorphism are linked to the sex chromosomes.

Spiders have funky sex-determination systems, but
they can still have gynandromorphs. The coloring is
different, but there’s more. It is hard to see, but only
the male side (purplish) has the palp organ growing
on the second appendage for the transfer of
reproductive cells. Image via: spider silk stockings
But wait – normal male and female fruit flies both have red eyes. Here one is red but the other is white. That’s because the gene for eye color and body color pattern in fruit flies is carried on the X chromosome too. If the loss of a chromosome leaves that side of the body with only one X (XO male) and the X it has carries the recessive white eye color gene, then that eye will be white. The other half (XX female) might have dominant red and recessive white eye genes on its two X chromosomes, so that eye would be red.

Is a bilateral difference in coloration enough to call an animal bilaterally asymmetric? They are phenotypically (how they look outwardly) asymmetric, but you cut them in half the silhouettes would be exactly the same (body plan is still symmetric). You can argue amongst yourselves as to what makes an animal bilaterally asymmetric.

Gynandromorphs in vertebrates are extremely rare. The reason for this is that sex characteristics aren’t only controlled by genes on the sex chromosomes. They are also under the control of hormones. But gynandromorphy does occur in birds – they’re vertebrates, but different somehow. No one is quite sure why gynandromorphs are possible for them.

It could be that the mistake comes when multiple male reproductive cells are successful in fertilizing one egg cell. When the fertilized egg cell divides, the daughters would probably be asymmetric with respect to sex chromosomes. Since the sex chromosomes control the production of the reproductive organs, and those organs then make the hormones, you can see how the two are linked.

The gynandromorphic chicken on the left is more a
mosaic than completely bilateral. The male side (your
right) has bigger breast muscle, leg spur, bigger wattle
and white feathers (see the sporadic darker feathers –
it’s a mosaic). A 2010 study showed that if you
transplanted male cells on to the female side, they
retained their secondary sex characteristics –hormones
ain’t everything. The cardinal on the right is striking –
the perfect Ball State University mascot.
The key is in determining which of the sexually dimorphic traits are under strictly genetic control and which are under hormonal control. A study in a gynandromorphic finch in 2003 showed that not everything is hormones. The brains of the males and females are different (in part this determines the song the bird sings) and gynandromorphic finches have brains that are half male and half female in structure. Even with hormones that circulate throughout the body, the brains are still different. The finch of the study sang a male song and mated with a female (no offspring). The male behaviors were controlled by the male part of the brain.

A very rare gynandromorphic cardinal was spotted and subsequently studied for 40 days from afar. The paper reporting this study stated that the bird never sang, never drew the attention of other birds, and never mated. It was a complete loner. But could he/she mate?

Most female birds have one horn of the uterus (left side) that is functional while the other is small and nonfunctional (makes them lighter for flight). Male birds usually have one long testis that is functional, the right one. Since neither male or female birds (most of them) have external reproductive organs, then a gynandromorph bird where the left half is female and the right half is male might actually have a shot at being fertile. It would all depend on how the hormone battle played out.

However, gynandromorphs in mammals don’t happen. The sex hormones control too much of the systems and flow throughout entire body, so you can’t really keep secondary sex characteristics limited to a geographically determined set of cells, even if the sex chromosomes are different in the cells.

Butterflies show sexual dichromatism (different colors
in males and females) and well as different morphologies
of wing (shapes), The gynandromorphs display both, so
they are truly bilaterally asymmetric. Butterflies have an
XX and XY (XO) sex determination system like fruitflies,
except here the XX’s are male.
But there are some characteristics that are hormone independent. Some sex characteristics are set BEFORE the sex determining genes on the sex chromosomes are turned on (reviewed here). The sex characteristic is a default, and therefore is seen both males and females despite later hormone differences. That’s why men have nipples. Nippled is the default state, no nipples isn’t possible. And three nipples is just weird.

The example I like to give for the bilateral gynandromorphy that shows true bilateral asymmetry is butterflies. The male and female often have different coloration and wing shape. This makes them sexually dichromatic within one animal but also bilaterally asymmetric.

Next week we’ll back to the butterflies and asymmetry. There’s one butterfly who is attractive to the girls precisely because he’s asymmetric.

Renfree, M., Chew, K., & Shaw, G. (2014). Hormone-Independent Pathways of Sexual Differentiation Sexual Development, 8 (5), 327-336 DOI: 10.1159/000358447

Dumanski, J., Rasi, C., Lonn, M., Davies, H., Ingelsson, M., Giedraitis, V., Lannfelt, L., Magnusson, P., Lindgren, C., Morris, A., Cesarini, D., Johannesson, M., Tiensuu Janson, E., Lind, L., Pedersen, N., Ingelsson, E., & Forsberg, L. (2014). Smoking is associated with mosaic loss of chromosome Y Science, 347 (6217), 81-83 DOI: 10.1126/science.1262092

Zhao, D., McBride, D., Nandi, S., McQueen, H., McGrew, M., Hocking, P., Lewis, P., Sang, H., & Clinton, M. (2010). Somatic sex identity is cell autonomous in the chicken Nature, 464 (7286), 237-242 DOI: 10.1038/nature08852

Peer, B., & Motz, R. (2014). Observations of a Bilateral Gynandromorph Northern Cardinal ( ) The Wilson Journal of Ornithology, 126 (4), 778-781 DOI: 10.1676/14-025.1

Ma, K. (2013). Embryonic left-right separation mechanism allows confinement of mutation-induced phenotypes to one lateral body half of bilaterians American Journal of Medical Genetics Part A, 161 (12), 3095-3114 DOI: 10.1002/ajmg.a.36188

For more information or classroom activities, see:

Sex-determination system –

Gynandromorphy -