The Wide, Wild World of Sex

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In the dramatic opening scene of Disney’s Finding Nemo, parents Coral and Marlin anxiously wait for their offspring to hatch. Their mood is light and hopeful, but the music signals an ominous shift. As a barracuda approaches the reef, Coral rushes to protect their eggs. Marlin is knocked unconscious as he tries to protect Coral. When he wakes, Coral is gone, and Marlin finds a single egg remaining from their large clutch. The egg hatches, and Marlin names his only child Nemo, a name chosen by Coral before her untimely death.

Now let a biologist, rather than a screenwriter, finish the opening scene.  Marlin not only finds himself a single parent, but he also begins to undergo a fascinating physical change from male to female, from Marlin to Marlina. This version is far more accurate and interesting than the one Disney presented.

The death of Nemo’s mother would have resulted in the transition of Marlin to Marlina.

Marlin is a clownfish, and clownfish sex determination is quite interesting. The female is the largest individual in a school of clownfish, and the breeding male is the second-largest. All other members of the school are smaller, nonbreeding males. Upon the death of the female clownfish, the dominant breeding male undergoes a sex change, becoming the new breeding female. Biologists call this change sequential hermaphroditism. As a result, the death of Nemo’s mother would have resulted in the transition of Marlin to Marlina. Perhaps the writers at Disney thought this twist, although fascinating, would have added too much complexity to the story line without advancing their plot?

MALE AND FEMALE JUST DON’T CUT IT

The variety of sexual systems in nature is complex and incredibly interesting. Many of us categorize sexes into what seem to e easily definable categories – male and female – but biologists consider this simple classification system woefully inadequate. There are variations in not only how organisms reproduce but also their sexual systems and mechanisms of sexual determination. In fact, when we look at the spectrum of sexual systems in Creation, the sequential hermaphroditism of clownfish is actually quite tame.

At its most basic level, sexual reproduction involves the fusion of gametes, or sex cells, to form a new individual. Gametes such as human eggs and sperm possess half the amount of genetic information found in other cells. The gametes of humans and many other plants and animals are categorized as eggs and sperm based on size and structure (eggs are larger and sperm smaller). However, these delineations don’t work for all organisms. In fungi, all gametes are typically the same size and shape, so they are referred to as plus and minus, rather than egg and sperm. As a result, some fungi reproduce sexually, but they do not have identifiable sexes. Regardless of the types of gametes employed, when two gametes fuse together, their genetic contents combine and a new and unique cell, the zygote, is created. This is the story of sexual reproduction. And in this story, we all begin as zygotes.

When discussing a biological view of sex, it is not only our understanding of gametes, sex-switching clownfish and seemingly sexless fungi that require expansion. There are individual organisms that produce both eggs and sperm at the same time, and these creatures are all around us. Plants are great examples. In most plants – pine trees, lilies, corn, lilacs and tulips – the same individual produces both eggs and sperm. Tulip plants produce gametes in bisexual flowers (the eggs in immature seeds and the sperm in pollen grains). A single pine tree produces pollen (i.e., sperm) in small papery cones and eggs in the seeds on large woody cones. If a bisexual plant “mates” with itself, is that still sexual reproduction? Of course! Sexual reproduction refers to the fusion of gametes, even if those gametes are produced by the same individual.

Earthworms, garden snails, tapeworms, corals and leeches are all simultaneous hermaphrodites – simultaneously supporting functional ovaries and testes and producing both eggs and sperm. Typically, these animals still require a mate for sexual reproduction. Consider common garden snails. When two garden snails meet, they exchange sperm with each other, efficiently enabling the eggs of both parents to be fertilized. However, because the energy cost of “being female” is higher than the cost of “being male,” some simultaneous hermaphrodites cheat – attempting to deposit their sperm without taking sperm from their partner. Hermaphroditic marine flatworms often participate in mating jousts – they rear up and strike each other, depositing sperm with each jab. The loser bears not only the scars of the battle, but also the cost of supporting their mutual offspring.

Among vertebrates, hermaphroditism is best observed in fish. Although a few fish species are simultaneous hermaphrodites, sequential hermaphrodites, switching from male to female function or from female to male function, are more common. Depending upon species, these changes might be part of the normal life history of the fish or might result from the loss of a mate or change in the environment. In addition to clownfish, parrotfish, wrasses and angelfish also switch sex. Parrotfish live in mating groups called harems, where a large distinctively colored male exerts control over several females. If the male is removed from the group, the most dominant female undergoes behavioral and color changes, taking over the harem. Over time, she completes the physical changes necessary to become a functional male, mating with the females in the harem.

TYPICAL GENDER FUNCTIONS

Among organisms that typically have separate male and female function, how is that function determined?  Again, biology can offer some interesting and unexpected answers. Honey bee and reptile sex are fascinating examples. When a virgin queen bee leaves the colony on her mating flight, her scent attracts male bees (drones) from neighboring colonies. In midflight, the queen mates with several drones, taking their sperm packets and storing them in her body. Spent and dying, the drones fall to the ground. The mated queen returns to the colony and begins to lay eggs. If she allows the eggs to be fertilized with the sperm in her body, female workers are produced. If she withholds sperm, the unfertilized eggs will give rise to drones. In the fertilized eggs of reptiles, the temperature of egg incubation determines the sex of offspring. Turtle eggs incubated at cool temperatures produce all males, while eggs incubated at warmer temperatures produce all females. Alligator eggs incubated at cool or warm temperatures produce all females, while intermediate temperatures produce males.

What about humans? To answer this question, more details are required. Typically, in human sexual reproduction, each gamete contributes 23 different molecules of DNA, or chromosomes, to the zygote. As a result, the zygote has 23 pairs of chromosomes, 23 from the egg and 23 from the sperm. Before the zygote can divide to produce two cells, each of the 46 chromosomes must be copied precisely and then precisely divided between the two new cells, insuring that each new cell has one of each of the 46 chromosomes. Through repeated division of these cells, you grew from a single-celled zygote into an incredibly complex creature composed of trillions of cells. You have 86 billion cells in your brain alone!

The formation of human gametes is a little more complicated than the formation of our other cells. Gamete formation only occurs in very specific locations, in the gonads – ovaries produce eggs, and testes produce sperm. Gonads also produce sex hormones important in the development of gametes and other sexual characteristics. Gamete formation requires that precisely one of each of the 23 pairs of chromosomes is divvied up into each gamete. The fusion of an egg and sperm produces a zygote with the proper number of chromosomes, 46. As with many biological processes, there is some wobble in the system. If chromosomes are not precisely divvied up into gametes, gametes will have too few (22) or too many (24) chromosomes. If one of these gametes is involved in fertilization, the resulting zygote will have too many (47) or too few (45) chromosomes. Down Syndrome is a well-known example of this, resulting when an individual has three copies of chromosome 21 and therefore a total of 47 chromosomes.

One chromosome pair, the sex chromosomes, typically determine the sex of the zygote. The sex chromosome of an egg is an “X” type, and that of the sperm may be an “X” or a “Y” type. If the zygote receives an X chromosome from the egg and from the sperm, it will be chromosomally female (XX). If the zygote receives and X from the egg and a Y from the sperm, it will be chromosomally male (XY). During the first weeks of development in the mother’s womb, the original, single-celled zygote divides again and again, forming tissues and organs, some of which will later become gonads. Interestingly, regardless of your genetic condition (XX or XY), early in development your gonads had the ability to become testes or ovaries. Once formed, the testes will produce testosterone, which is involved in the development of male traits. If ovaries are formed, they will produce estrogen to feminize the embryo.

Not every human’s sex determination is straightforward, however. In fact, much of what we know about human sex determination is from studying atypical situations. Some human sex determination variants are caused by chromosomal abnormalities. As mentioned earlier, mistakes can occur during gamete formation, resulting in too few or too many chromosomes. If the missing or extra chromosome in the gamete is a sex chromosome, the zygote will carry one extra sex chromosome (XXX or XYY) or will be missing a sex chromosome (X only or Y only).

Individuals with a single X chromosome have Turner Syndrome. These women have rudimentary ovaries, underdeveloped breasts and are infertile. In addition, because they do not have functional gonads, they do not produce female sex hormones. Embryos that carry only a Y chromosome (45 total chromosomes) are not viable. Klinefelter Syndrome affects 1 in 500 to 1 in 1,000 newborn males. These individuals carry two X chromosomes and one Y chromosome (47 total chromosomes).  Affected individuals have small testes and reduced testosterone production leading to incomplete puberty and breast enlargement. Men with Klinefelter Syndrome are infertile. In contrast, women with an extra X chromosome (XXX) and males with extra Y chromosomes (XYY) develop normally and are fertile.

Sex-chromosome abnormalities show scientists that the presence of a Y chromosome is important for the development of male sex characteristics. The SRY gene, normally found only on the Y chromosome, acts as a master switch in sex determination during embryonic development. In rare cases, during sperm formation, a piece of the Y chromosome carrying the SRY gene can be transferred to the X chromosome. If an egg is fertilized by a sperm with an SRY-modified X chromosome, the resulting zygote will develop into a normal male, even though its chromosomal sex is female. Furthermore, a baby carrying one normal X chromosome and a Y chromosome lacking the SRY gene will develop as a normal female even though its chromosomal sex is male. Parents-to-be looking at the results of an amniocentesis (which looks at chromosomes) and an ultrasound (which looks at organs and structures) would see contradictory results.

WHAT IS GENDER?

These examples lead us to this question: What defines sex in humans? Does the presence of certain chromosomal combinations, XX or XY, define sex? Does the presence of a specific gene (SRY) define sex? Does the presence of particular gonads define sex (ovaries or testes)? Do genitalia define sex? There is actually more to the story. Tighten your thinking cap and read on.

Clinicians estimate that 2 to 5 in 100,000 people are born with complete Androgen Insensitivity Syndrome. People with complete AIS have an X and a Y chromosome. Their Y chromosome has a functional SRY gene. The SRY gene directs the development of male gonads (testes). The testes produce male sex hormones as a signal for development of other male characteristics. AIS occurs when the testes produce but the embryo cannot respond to male sex hormones. The cells that should receive these hormonal signals cannot recognize it. As a result, female genitalia develop. People with AIS, therefore, have male gonads (testes) but their testes remain in the pelvic cavity, they have female external genitalia, a vagina, but no uterus. In other words, their genetic and gonadal sex is male, but their external genitalia are female. What is their “biological sex”? Both? Neither?

One last sex-determination variant that illustrates how difficult it can be to assign a biological sex is 5-Alpha Reductase Deficiency. This condition is so rare that scientists do not have an estimate of its frequency; however, large families with affected family members have been studied extensively. People with 5-Alpha Reductase Deficiency are genetically male (XY). Their Y chromosome has a normal SRY gene, and the SRY gene directs the development of testes. Another gene, however, produces an enzyme that fails to function. Normally this enzyme, 5-alpha reductase, catalyzes the production of a very potent male sex hormone (dihydrotestosterone, or DHT) from testosterone. DHT is required for the testicles to descend from the abdomen and for the formation of male external genitalia. If the 5-alpha reductase enzyme is defective, DHT is not produced. Without DHT, genetic males are born with genitalia that appear female, genitalia that are ambiguous or a micropenis (with a urethra that opens on the underside rather than the tip).

Most babies born with 5-Alpha Reductase Deficiency are raised as girls even though their chromosomal and gonadal sex is male. Because they have testes, at puberty the testes begin to secrete large amounts of testosterone, leading to the development of some male characteristics expected at puberty but also to some characteristics that should have developed earlier. Their voice changes, they experience a growth spurt and increased muscle mass typical of a male. Additionally, their micropenis (or clitoris if they were raised as a female) along with the scrotum (or labia if raised as a female) grow larger, more closely resembling a small penis. Some of these individuals, although raised as girls, identify more with and adopt a male gender in early adulthood after these dramatic changes at puberty occur.

SO, THEN . . .

Why is any of this information important to consider? Does it inform our understanding of sexual orientation? No. Sex determination and sexual orientation are not the same. We are not addressing sexual orientation. Is this essay about transgendered individuals? Again, no. Transgendered people and the kinds of biological variants we describe are not the same. We are simply shining light on a corner of the natural world, the beautiful complexity that exists in that small corner and inviting you to see and reflect on that complexity with us.

As Christian biologists, we take both God’s revelation in Holy Scripture and God’s revelation in the natural world seriously. The concept of the two books of revelation echoes through our theological history. John Calvin called the two books special and general revelation. In his Institutes of the Christian Religion, Calvin attests to general revelation saying, “God, then, reveals Himself through His works.” Calvin supports his claim by citing Scripture, including Romans 1:19-20 and Psalm 19:1-2: “The heavens declare the glory of God, and the sky above proclaims his handiwork. Day to day pours out speech, and night to night reveals knowledge.”

The Belgic Confession, a doctrinal standard for the Reformed Church in America, the Christian Reformed Church and several other denominations, articulates in Article 2 two ways we come to know God:

“We know God by two means: First, by the creation, preservation, and government of the universe; which is before our eyes like a beautiful book, in which all creatures, great and small, are as letters to make us ponder the invisible things of God: God’s eternal power and divinity, as the apostle Paul says in Romans 1:20. All these things are enough to convict humans and to leave them without excuse. Second, God makes himself known to us more clearly by His holy and divine Word, as much as we need in this life, for God’s glory and for our salvation.”

Special revelation teaches us about the covenantal relationship God established with the people of Israel and about the fulfillment of that covenant of grace in the sacrificial death and resurrection of God’s son, Jesus Christ. Only in special revelation do we see God’s covenant of grace in the person of Jesus. It is the shining example of how special revelation makes God “known to us more clearly” in Scripture compared to general revelation, which may point us generally to a creator but does not reveal Jesus specifically (Belgic Confession, Article 2, emphasis added).

Does this negate the value of general revelation? As Christians and biologists, we answer with an emphatic no! We believe that in addition to pointing us to a creator, God’s general revelation can shed light on how we should live in our world as faithful followers of Jesus Christ. We spend time studying general revelation in the field and laboratory, examining the details of God’s amazing creation. Those details include learning about and from the incredible diversity of sexual systems we see in other creatures and the exploration of molecular mechanisms of sex determination in humans. When we attend carefully to both God’s special and general revelation, we are compelled to think deeply about some difficult questions.

CONCRETE CONSEQUENCES

Since 2013, 24 states have introduced legislation that would restrict access to bathrooms or locker rooms based on a person’s “biological sex.” This year, H.R. 2796 Civil Rights Uniformity Act of 2017 was introduced. This piece of legislation requires the words “man” or “woman” to be interpreted to refer exclusively to a person’s genetic sex for purposes determining the meaning of federal civil rights laws or related federal administrative agency regulations or guidance.

As biologists, we understand that sexual determination is a beautifully complex process. But when we hear legislative proposals based on biological sex, we know that this complexity is not being acknowledged. What exactly is “biological sex”? Even experts have a hard time providing a simple answer to  that question. It is more difficult when “biological sex” is used in legislation. Are we painting everyone with a broad brush that is inadequate because many of the conditions described earlier blur a clear dimorphic (male-female) characterization?

Scripture teaches us in Matthew 25:31-46 that Christ cares for the least of these. Is it reasonable to assume that Christ cares for the different of these as well? Because of rare mutations, some of our neighbors or perhaps even some of our children, do not fit neatly into one of two easily defined categories. Some of our neighbors have AIS or Klinefelter syndrome. Do we see people with 5-Alpha Reductase Deficiency as precious children of God, made in God’s image? For people of God, does a deeper understanding of the variation in sex types and sex determination influence the way we love our neighbors and are witnesses of Christ to them? Rather than using our narrow human categories, perhaps we should focus on the words of Paul from 1 Corinthians 12:13, acknowledging that our identities are not determined by whether we are free or slave, male or female, but rather by our value as children of God, heirs of the covenant of grace in Jesus.

Laura Furlong, Elizabeth Heeg and Sara Sybesma Tolsma spend their days exploring the beautiful complexity of God’s general revelation and sharing that beauty with students at Northwestern College, Orange City, Iowa.

Photo: Nick Hobgood, CC BY-SA 3.0, Wikimedia Commons.