Battle of the Sperms

Inside every Drosophila melanogaster (fruit fly) female is a battleground where sperm can jockey with each other for the honor of fertilizing her eggs. By sequentially mating females with males genetically-engineered to produce sperm that glow either green or red (see video below), scientists have been able to directly observe sperm from two different males competing in what resembles a fruit fly version of Tron. Color coding the sperm in this way allows researchers to distinguish one male’s sperm from another’s and determine who the winners are.

“Sperm from two different males genetically-engineered to express either green or red fluorescent proteins compete within the female reproductive tract of the fruit fly Drosophila melanogaster.”

Surprisingly, it’s not always the fastest sperm that wins.

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The problem with gender verification in the Olympics.

At the London 2012 Olympics Opening Ceremony, Caster Semenya had the honor of carrying South Africa’s flag. This week, she makes her Olympic debut (qualifier preliminary heat spoiler alert) representing her country in the 800m and 1500m events. This is in stark contrast to 3 years ago, when Semenya was banned from competition by the IAAF after cruising her way to gold in the 800m at the World Athletic Championships in Berlin. Combined with her physical appearance, Semenya’s dominating performance came at a price, fueling speculations that she was not, in fact, a woman. After her victory, Semenya was barred from competing until her gender was verified by genetic testing. As you will see, this can be subjective and unreliable (You can try for yourself using the HHMI’s biointeractive gender test).


Humans have two sex chromosomes designated as X and Y chromosomes. Females have two X chromosomes (XX) while males have one X and one Y chromosome (XY). One of the major factors that initiates male sex determination is a protein called Testis-determining factor, which is encoded by the SRY (Sex-determining region Y) gene normally found only on the Y chromosome. So, at first glance it would appear that a simple sex chromosome test would suffice to verify sex. 

In humans, females have two X chromosomes and males have one X and one Y chromosome. The Sex-determining region Y (SRY) gene drives male sex determination and is found on the Y chromosome.

However, the  line delineating sex is not so rigid– disorders of sex development (DSD) can complicate reconciling genetics with gender and sex. For instance, in Swyer syndrome, individuals appear outwardly female and have a normal uterus and Fallopian tubes, despite having the  male sex chromosome karyotype (number and appearance of chromosomes in the cell): XY. This condition arises when the SRY gene on the Y chromosome has either been lost or mutated and, as a result, male sex determination cannot be initiated. Instead, these individuals develop physically as females. 

Male sex determination cannot be initiated because the SRY gene is either mutated or lost.

On the other hand, an individual with an XX karyotype can develop as male is if one of the X (X*) chromosomes abnormally carries the SRY gene. The SRY gene can find its way from the Y to the X chromosome through chromosomal crossover, a phenomenon where corresponding chromosomes exchange parts with each other to generate new, unique chromosomes. This usually occurs during meiosis, a specialized form of cell division that gives rise to either sperm or egg. Crossovers ensure that different combinations of paternal genes are packaged into sperm and different combinations of maternal genes are packaged into eggs. This recombination of chromosomes is the reason why we look different from our siblings (exception: identical twins) and is generally good because it increases genetic diversity.

Recombination between the X and Y chromosomes normally occurs only at the tips of the chromosomes, beyond the region that encompasses the SRY gene. However, sometimes recombination can go awry and crossing over occurs such that the SRY gene is moved to the X chromosome. Since the SRY gene is located on the Y chromosome, the abnormal recombination event that results in an X* chromosome must occur in the father of an XX individual. The presence of the SRY gene, even in the absence of a Y chromosome, is sufficient to initiate male sex determination.

Abnormal recombination in the father of XX males, results in an X chromosome that carries the SRY gene (designated X*). Reproduction involving sperm that carry the X* results in XX* males since the presence of the SRY gene, even in the absence of a Y chromosome, can initiate male sex determination.

Given the importance of the SRY gene in male sex determination, one might expect a test that detected the presence of SRY would be adequate to verify gender. But even this test has it’s problems. For one, the test is subject to false positives since it can detect the presence of a mutated, non-functional SRY gene. There are also conditions which can override male development, even when the SRY gene is present. Such was the case for “8 of 3,387 female athletes” who tested positive for the SRY gene, but were allowed to compete at the 1996 Atlanta Olympics. In addition to carrying SRY, these 8 athletes also had a condition known as androgen insensitivity syndrome (AIS), which rendered them insensitive to the effects of male hormones such as testosterone.

Now, the International Olympics Committee (IOC) is pivoting away from gender verification to what they consider testing female “eligibility” by measuring levels of naturally occurring testosterone, a hormone classically associated with masculinity. This is not to be confused with tests that detect synthetic testosterone used for dopingUnder the IOC’s new rules, “women with levels of testosterone that reach a man’s [emphasis mine] normal level will be barred from competing with other women if it is found that the athlete’s body is responsive to androgens.” Still sounds like a gender verification test to me.

Testosterone

Unfortunately, testosterone is also an unreliable standard. For one, some women have abnormally high levels of testosterone, a condition known as hyperandrogenism. Secondly, as Rebeeca Jordan-Young and Katrina Karkazis write in the New York Times, “Testosterone is one of the most slippery markers that sports authorities have come up with yet. Yes, average testosterone levels are markedly different for men and women. But levels vary widely depending on time of day, time of life, social status and — crucially — one’s history of athletic training. Moreover, cellular responses range so widely that testosterone level alone is meaningless.” It’s also unclear whether higher levels of testosterone is a key factor in athleticism in women. Lastly, androgen insensitivity syndrome (AIS), or the inability to respond to male hormones such as testosterone, is overrepresented in women athletes. 

Testosterone testing, and gender verification in general, also reeks of sexism and discrimination, reinforcing not only perceptions of what a women should look like but also placing limits on what women can physically achieve**. Jesse Ellison of the Daily Beast writes,

“It all highlights a cruel injustice: the policy—and the testing, treatment, and humiliation that can come with it—only applies to female athletes. Men who excel at, say, ice dancing or synchronized swimming, where success has more to do with grace and rhythm than brute strength or speed, simply aren’t questioned in the same way women are. In 2010, after two French-Canadian sports commentators snickered over the flamboyant skating champion Johnny Weir and suggested that he should compete with the women, they were immediately and vociferously condemned for what was widely perceived as homophobic, despicable language. (This was, keep in mind, precisely the moment that Semenya was living in virtual exile after the subject of her gender had made international news.) Similarly, there is no upper—or lower, for that matter—limit to the amount of testosterone their bodies naturally produce.”

All of which raises the question: If the IOC feels that high levels of natural testosterone offer an unfair advantage, then will they apply an eligibility policy to men as well?

China’s Ye Shiwen after winning gold in the women’s 200 IM.
Photo by Adam Pretty/Getty Images

Note: On the use of gender, Wood and Stanton: “Unfortunately, ‘gender verification’ is a misnomer that confuses the distinction between sex and gender. Sex is a biologic definition that distinguishes male and female; gender is the sense of one’s own self as a man or woman.”

** While the speculations surrounding Chinese Olympic swimmer, Ye Shiwen, is the suspicion of doping and not gender, it should be noted that it has been framed within the context of gender since in the “final 50 meters of the IM’s freestyle leg, she swam faster than Ryan Lochte did in that portion of his gold-medal-winning 400-meter IM.”

References
1) Eggers S, Sinclair A. Mammalian sex determination—insights from humans and mice. Chromosome Res. 2012 Jan;20(1):215-38. Review. PubMed PMID: 22290220; PubMed Central PMCID: PMC3279640. http://www.springerlink.com/content/w346t6168534728l/

2) Wood RI, Stanton SJ. Testosterone and sport: current perspectives. Horm Behav.2012 Jan;61(1):147-55. Epub 2011 Oct 1. Review. PubMed PMID: 21983229; PubMed Central PMCID: PMC3264812. http://www.sciencedirect.com/science/article/pii/S0018506X11002212

Related Reading:

Olympic inequality: Studies show Olympics commentary differs based on gender, race and nationality

Sex Hormones! The Chemistry Behind Testosterone Doping

 

by Viet Le

It’s a Male. It’s a Female. No…it’s a Gynandromorph!

Don’t eat me cuz I’m beautiful…

You could make a case for “looking weird” being an effective survival strategy. Just ask Calvin the lobster whose calico-patterned shell spared it from dining table destiny. Rather than being dunked into a pot of boiling water, Calvin is now on display at the New England Aquarium. Calico-patterned lobsters are extremely rare, occuring about 1 in 30 million. For comparison, the rarest are albino lobsters, which occur at a rate of about 1 in 100 million whereas blue lobsters are more commonly found (~1 in 2 million).

But even stranger looking lobsters are lurking out there in our oceans. Take for instance this two-toned lobster that looks like only one half of it was cooked :

As odd as this lobster looked initially, the more I looked at this picture the more familiar it seemed to me. Where have I seen something like this before? I paced around the lab a bit yesterday and it dawned on me. I’ve seen something like this happen in Drosophila. Every once in a while I’ll find a fruit fly where one half of its body is yellow and other half is brown–split right down the middle. Or more strikingly one eye is white and the other is red. And what’s even more peculiar, one half of the fly will be male with male specific structures like the sex comb and the other half is female. The genitalia of these individuals can vary from having “two complete sets of genitalia, one male, one female. Most of the time, you get weird mish-mashes of tissue that don’t look like male or female genitalia (h/t @DaveMellert).” This bilateral sexual asymmetry is a form of gynandromophy, where an organism abnormally displays both male and female characteristics and is not to be confused with hermaphrodites which are organisms that have both male and female sexual reproductive organs.

Drosophila gynandromorph

In Drosophila, sex is determined using the XX/XY sex-determination system (also used in humans) in which females have 2 X chromosomes and males have 1 X chromosome and 1 Y chromosome. Bilateral gynandromorphy in Drosophila occurs when there is a spontaneous, anomalous loss of an X chromosome during the first mitotic division in a female zygote. This results in one daughter nucleus* containing 2 X chromosomes (denoted as XX) and the other daughter nucleus containing only 1 X chromosome (denoted as XO). In this situation, cells derived from the XX nucleus will give rise to the female body plan in half of the fly while cells derived from the XO nucleus will give rise to the male half despite the lack of a Y chromosome. This is because in Drosophila the most important factor in sex determination is the number of X chromosomes. This phenomena also indicates that by the first mitotic division the left and right side of the Drosophila has been determined since one half will become male and the other female. All of the descendants of one cell will makeup the entire left side of the animal while all the descendants of the other cell will makeup the right side!

XX/XY sex-determination system in Drosophila

Although this explains how bilateral sexual asymmetry occurs, you might be wondering why in the Drosophila gynandromorph above one half of its body is yellow (left) and the other is brown (right) or why one eye is white and the other is red. This is because the genes that determine eye and body color are found on the X chromosome. So in the case of eye color, the original zygote was heterozygous for the gene controlling eye color–it has the recessive allele or gene variant for white eyes (w) on one X chromosome and the wildtype allele for red eyes (w+) on the other X chromosome. During mitosis, one of the w+ -bearing X chromosomes is lost and so cells derived from this XO nucleus will carry only the white eye gene, therefore giving rise to 1 white eye. The other eye is heterozygous for the eye color gene, but since w is recessive the eye will be red by virtue of also carrying the wildtype w+ allele. Of course, loss of the X chromosome can also occur after the first mitotic division, in which case the animal will be a mosaic gynandromorph having patches or regions that are male or female instead of the stark left-right division of male and female body plans.

Gynandromorphy occurs in other animals also, although the specific details depend on the species in question. In butterflies, gynandromorphy is a result of sex chromosome aneuploidy as well but their situation is reversed: XX cells are male and XY or XO cells are female.

In birds, however, gynandromorphy occurs by a different process. Sex determination in birds is different from insects and humans: females have a Z and W chromosome whereas males have 2 Z chromosomes. This chicken is a mosaic of both normal male (ZZ) and female (ZW) cells, with male cells concentrated on 1 side and female cells concentrated on the other.

The exact details of this phenomena in birds is unknown. One hypothesis is that it is due to an error that “occurs in the formation of an egg, which normally carries one chromosome to unite with the single chromosome carried by the sperm. But if an egg accidentally ends up with two chromosomes — a Z and a W — and if this aberrant egg is fertilized by two Z-carrying sperm, the bird that results will have some ZZ cells and some ZW cells, he explained.” Another hypothesis is that the egg is abnormally fertilized by two sperm. 

Coming back to lobsters, bilateral gynandromorphs can occur in crustaceans as well. As for humans, however, despite Conrad Lycosthenes’s claims that a bilateral human gynandromorph existed, Natalie Reed explains why this phenomena in all likelihood would not happen, “Back to this not happening in humans: yes, intersexual chimerism can happen in humans. You can even end up with human beings who have one ovary and one testicle. But given that almost all sexual differentiation is a result of hormones, which are more or less evenly distributed throughout the body, you would never see any kind of stark split down the middle of a human with, say, a breast on one side and a flat chest on the other.”

*I say nucleus rather than cells because Drosophila do this strange thing during early embryonic development where the chromosomes duplicate and segregate into separate nuclei without the normal cell division (cytokinesis) that occurs after mitosis. This results in a cell called the syncytial blastoderm that has multiple nuclei without cell membranes separating the nuclei from each other. After 13 rounds of nuclear divisions, cell membranes are finally erected (cellularization) to partition the nuclei into individual cells.

Here is a video of mitosis in the early Drosophila embryo. Note the lack of cell membranes.

Here is a video of cellularization.