11.1 Understanding Sexual Reproduction and Sexual Dimorphism

Neuroscience across species: Evolution of Sexual Reproduction and Sexual Differentiation

Sexual reproduction is a fundamental process found across species from single-celled protists to all plants, fungi, and animals. As you can tell, sexual reproduction is incredibly common and a crucial part of today’s life on Earth! But what is sexual reproduction and why is it so widespread?

To understand the fundamentals of sexual reproduction, we must first review how cells carry genetic information. Genetic material is stored in DNA (deoxyribonucleic acid), organized into structures called chromosomes (see Figure 11.2 top panel). These chromosomes are kept within the cell’s nucleus.

Figure 11.2 DNA and mitosis

Most cells in animals and plants are diploid, meaning they contain two sets of chromosomes: one inherited from each parent (we will go over how that works later in this section). This is why we often refer to having “23 pairs” of chromosomes in humans, rather than stating a total of 46. Every diploid cell in our bodies contains the exact same genetic information—exact copies of all chromosomes. But how is this uniformity achieved? The process begins at the very start of an individual’s life, starting from a single cell. To replicate itself, this cell first precisely duplicates each of its 46 chromosomes, resulting in two identical structures known as sister chromatids for each chromosome. Once every chromosome has been copied, the cell initiates mitosis, a type of cell division in which sister chromatids are evenly divided into two daughter cells, ensuring that each new cell receives a complete set of chromosomes (Figure 11.2 bottom panel). This division results in two identical diploid cells, each capable of further undergoing mitosis. Mitosis is crucial for the growth, development, and maintenance of multicellular organisms.

But you also learned that each copy of the chromosomes is inherited from one parent. This is possible thanks to sexual reproduction. So how does it work? At its most basic, sexual reproduction involves the steps shown in Figure 11.3: 1. Gamete Production: It all starts when each parent produces special reproductive cells called gametes—sperm in males and eggs in females. These aren't your typical diploid body cells; they're haploid, meaning they carry just one set of chromosomes. This haploidy is the result of a unique type of cell division known as meiosis, distinct from mitosis. Meiosis is special because it includes two rounds of genetic shuffling and cell division, but only one round of DNA replication. During the first division (meiosis I), the chromosomes that have already been duplicated are divided up into two new cells, each receiving one half of each chromosome pair. In the second division (meiosis II), which is similar to mitosis, the sister chromatids (the two identical halves of each duplicated chromosome) are separated. The end product? Four unique haploid gametes, each containing half as many chromosomes as the original cell. 2. Fertilization: Next comes the magic of fertilization, where two haploid gametes (one sperm and one egg) merge. This fusion creates a genetically unique, diploid cell known as a zygote. 3. Development: From there, the zygote embarks on an incredible journey, dividing through mitosis and differentiating into specialized tissues and organs, ultimately growing into a new individual.

Figure 11.3 Meiosis and sexual reproduction

You might be asking yourself, why do organisms go through the complex process of producing specialized reproductive cells, searching for a compatible mate, and ultimately producing just one offspring by merging two gametes? Why not simply use mitosis to create genetically identical offspring, which seems much simpler and less risky?

There are two main hypotheses explaining this phenomenon. The first suggests that sexual reproduction evolved as a way to mask the expression of harmful mutations, effectively buffering genetic defects within a population (Michod and Gayley 1992). The second proposes that sexual reproduction serves as a mechanism to increase genetic variation, thus equipping organisms with the ability to adapt more rapidly to changing environmental conditions (McDonald, Rice, and Desai 2016). To understand how this works, we need to consider what it means to have two copies of each chromosome, one inherited from each parent.

First, due to the diploid nature of sexually reproducing organisms, where each parent contributes one version of each chromosome, or an allele, sexual reproduction plays a crucial role in shielding organisms from harmful mutations. Imagine if a harmful mutation is passed down from one parent; the normal allele from the other parent might counteract this defect, maintaining a healthy appearance or phenotype in the offspring. On the other hand, asexual reproduction, which clones the parent to produce offspring, doesn't provide this safeguard. Since the offspring are genetic copies of the parent, any mutations are directly passed on without the possibility of being diluted by a normal allele from another parent. Consequently, harmful mutations are more likely to show up and affect the organism, as there’s no genetic variation to help mask their effects.

Second, diploidy can contribute to genetic diversity. There are two main ways diploidy generates this increased diversity. First, diploidy allows for generation of offspring which collectively can have differing combinations of alleles for an individual gene. Consider a hypothetical example involving thermal tolerance in fish—a trait that might be influenced by different alleles. For simplicity, let's assume there are two alleles: one for low thermal tolerance (T), which is dominant and allows the fish to thrive in cooler waters, and one for high thermal tolerance (t), which is recessive and makes the fish more suited to warmer waters. Suppose both parents are heterozygous, carrying one T allele and one t allele. Because the T allele is dominant, these parents can comfortably handle cooler temperatures. When these fish reproduce, their offspring inherit various combinations of these alleles, which we can visualize using a Punnett square (Figure 11.4). In this scenario, approximately 50% of the offspring will inherit one T and one t allele, mirroring the thermal tolerance of their parents. About 25% will inherit two T alleles, potentially enhancing their tolerance for even colder temperatures than their parents can handle. The remaining 25% will receive two t alleles, making them better adapted to warmer waters. If environmental changes lead to warmer river temperatures, the offspring with a higher tolerance for heat are more likely to survive and reproduce. Over time, this could result in a population that is better adapted to the new, warmer environment. Without this genetic variation resulting from sexual reproduction, the fish population would be less capable of adapting to such changes.

Figure 11.4 Punnett square

The second way genetic diversity is increased during meiosis I happens in a process called homologous recombination. The top panel of Figure 11.3 (step 1) diagrams an overview of this idea, showing how pieces of the two parental copies of a chromosome in a developing gamete swap places, resulting in two new chromosomes that each contain a unique mix of sections from the parental chromosomes. This mixing creates new combinations of genes that are not found in either parent. As a result, each gamete formed during meiosis carries a unique set of genetic instructions. This genetic diversity increases the likelihood that offspring will have genetic variations, some of which may be beneficial for survival in a changing environment.

So now we know why sexual reproduction may have evolved; to protect against harmful mutations and to enhance genetic diversity. However, this doesn’t explain why most species have two distinct gametes. If organisms produced identical gametes—for instance, if all individuals only produced eggs instead of eggs and sperm—the eggs could theoretically fuse together to form a diploid zygote. This method would seem less costly because it wouldn’t limit individuals to mating only with those of a different type, thus expanding the potential pool of reproductive partners. So, why do most organisms have two distinct gametes?

One hypothesis proposed is that gamete types serve to avoid inbreeding by preventing fertilization between genetically identical or closely related members (Czárán and Hoekstra 2004). To illustrate this, consider a population of aquatic organisms where no distinction exists based on gamete types. In this scenario, all individuals release their gametes into the water, where any gamete can fuse with any other gamete. This lack of discrimination could lead to gametes coming from the same parent inadvertently fusing, undermining the benefits of sexual reproduction—namely, the reduction of harmful genetic mutations and the promotion of genetic diversity. Therefore, a population of organisms producing two distinct gamete types, each of which can only fuse with the opposite type, may have had an evolutionary advantage by reducing the likelihood of clonally related gametes fusing and thus promoting genetic diversity.

Interestingly, the existence of two distinct gametes profoundly influences the evolution of both physical and behavioral differences between sexes in many species, leading to a phenomenon known as sexual dimorphism.

Sexual Dimorphism

You may have noticed that in many species, males and females exhibit distinct physical features. For example, it is more common for male lions display a mane than female lions, and male Northern Cardinals are bright red with a distinctive crest and a loud, clear song, while females are pale brown with a slightly reddish tinge and a more subdued call (Figure 11.5). This phenomenon, known as sexual dimorphism, is prevalent throughout the animal kingdom and often extends beyond primary sex traits (i.e., traits directly involved in sexual reproduction, such as gonads or reproductive organs). But what drives these differences between males and females, and what purpose do they serve?

Figure 11.5 Examples of sexually dimorphic external physical appearances in nature Image credit: Lions by safaritravelplus - https://www.safaritravelplus.com/images/wildlife/lion-lioness/, CC0, Cardinals by Mike's Birds/Flickr, CC BY SA 2.0

Before we dive in, it's essential to grasp the concept of natural selection. Natural selection is a key mechanism in evolution where individuals with certain traits that are beneficial in their environment tend to survive and reproduce more successfully than others. This process begins with genetic variation within a population, where different traits—such as tolerating higher or lower water temperatures in the fish example we discussed—can significantly influence an individual's survival. Those who survive longer have more opportunities to reproduce, and therefore pass these advantageous traits to their offspring. On the other side, if a trait does not help the individuals’ survival, this individual will likely not get a chance to reproduce and therefore, over time, this trait may be lost. This leads us to a special subset of natural selection known as sexual selection, which focuses on traits that are advantageous for mating rather than just survival. These concepts can help us understand the classical view of why sexual dimorphism is so widespread.

This view, first proposed by Darwin (Darwin, Bonner, and May 1981) and further developed by an English geneticist Angus John Bateman (Bateman 1948), centers on the observation that in most sexually reproducing species, males produce many small, mobile gametes (sperm), while females produce fewer, larger, and less mobile gametes (eggs), although accumulating studies suggest that this phenomenon is more complex than initially thought (Clutton-Brock 2007). As an example, look at Figure 11.6 to see the relative size of a mouse egg surrounded by many sperm. Because sperm production is relatively inexpensive energetically, males have the potential to fertilize multiple females, a strategy that minimizes their investment in any single offspring (Trivers 1972). This leads to intense competition among males for access to mates. When two individuals of the same sex compete for access to the opposite sex, this is known as intrasexual selection, a type of sexual selection. Because of male-male competition, males often develop secondary sex traits that enhance their competitiveness in obtaining mates, such as larger body size, elaborate ornamentation, or dominant behaviors.

Figure 11.6 Female versus male gametes A mouse egg surrounded by many sperm exemplifies the difference in gamete size between females and males. Image credit: Image from Paul M Wassarman, Eveline S Litscher (2022) Female fertility and the zona pellucida eLife 11:e76106. CC BY 4.0

One notable example of intrasexual selection driving male-biased physical and behavioral traits is observed in elephant seals (Mirounga angustirostris). During the breeding season, male elephant seals gather on beaches to establish territories and compete for access to females. These males use their behavior, size, and strength to intimidate rivals and establish dominance. The bigger and more dominant males can mate with multiple females, while less dominant males are often excluded from mating opportunities (Le Boeuf, 1974) (Figure 11.7). As a result of this biased reproductive success, male elephant seals have evolved to be much bigger and dominant than females. This is intrasexual selection because females do not choose their mates; rather, it is the strength and dominance of the males that determine their access to females.

Figure 11.7 Male and female elephant seal Male elephant seals can weigh up to 10 times more than females. Image credit: By original image by Jan Roletto, uploaded 18:58, Feb 26, 2004 - de:Wikipedia by de:User:Baldhur, edited by Matthew Field - National Oceanic and Atmospheric Administration (http://www.noaa.gov), Public Domain, https://commons.wikimedia.org/w/index.php?curid=3440642

In contrast to males, females in most species are constrained in their reproductive potential by producing a finite number of energetically expensive gametes. Consequently, females typically invest more time and resources in parental care (Trivers 1972) and exhibit greater selectivity in mate choice, preferring to mate with males that possess the most favorable genetic or phenotypic traits. This one-sided mate selectiveness is known as intersexual selection.

A compelling example of intersexual selection are Satin Bowerbirds (Ptilonorhynchus violaceus). In this species, the females, who are solely responsible for rearing the young, also make critical mating decisions. Their choice of partner is heavily influenced by the male's ability to construct and decorate elaborate structures known as bowers. These bowers are not merely nests, but elaborate displays crafted from twigs and adorned with an array of colorful objects collected by the males. Additionally, the males perform intricate courtship displays, which include unique dances and a variety of vocalizations. To see a video of these behaviors, look here: link to https://www.youtube.com/watch?v=nWfyw51DQfU. Females prefer males who excel not only in their architectural skills but also in their performance abilities. This preference drives the evolution of increasingly complex bower designs and more sophisticated courtship behaviors, which comes at a cost to the male. This is intersexual selection because females actively choose their mates based on these elaborate displays and behaviors, influencing the traits that evolve in males (Borgia 1985).

While there are many examples of male-biased development of secondary traits, it's important to note that this is not always the case. An interesting example of female-biased development of secondary traits is the spotted hyena (Crocuta crocuta). Spotted hyenas are social animals that live in large communities called "clans," where females and males have distinct dominance hierarchies. In this species, females typically dominate males, with even low-ranking females often dominating high-ranking males. Females exhibit high levels of aggressiveness and develop virilized genitalia that closely resemble male genitals, with the clitoris forming an erectile pseudo-penis (Goymann, East, and Hofer 2001). As another examples of non-male bias in secondary traits, there are also many species where males and females are almost indistinguishable, and both contribute to raising their young. For instance, the California mouse (Peromyscus californicus) is a monogamous rodent in which both males and females share parental responsibilities, are similar in size and weight, and both aggressively defend their shared territories (Ribble 2003).

Lastly, a very interesting concept within sexual selection is sexual conflict, which occurs when the reproductive interests of males and females diverge, leading to evolutionary arms races between the sexes. A striking example of this is seen in the genitalia of ducks. In many duck species, males have evolved long, corkscrew-shaped penises, which facilitate forced copulations. In response, females have developed complex, labyrinthine vaginal tracts that can control the outcome of these forced encounters. This intricate anatomy allows females to limit successful fertilization to preferred males, despite the coercive strategies of others. This evolutionary battle between male persistence and female choice exemplifies how sexual conflict can drive the development of highly specialized and often bizarre reproductive traits in both sexes.

Moving beyond these examples, it's clear that both intersexual and intrasexual selection, as well as sexual conflict, which can all occur simultaneously in most species, have played significant roles in shaping distinct physical and behavioral traits in females and males over evolutionary time. However, sex differences encompass more than just sexual dimorphism related to reproductive success. They may arise as secondary consequences of traits linked to reproductive success, from trade-offs between reproductive investment and other biological functions, or from various social and environmental factors, among others. Regardless of the underlying causes, we are increasingly discovering that sex differences are present in a wide spectrum of physiological and behavioral characteristics. As we will explore, these differences have profound implications for our understanding of health and disease in both human and non-human animals.

Sex Differences in Non-Sexual Traits

Before delving deeper into sex differences, it is crucial to distinguish them from sexual dimorphism. Sexual dimorphism, which we focused on in the previous section, refers to the presence of two distinct forms of a characteristic (behavioral, physiological, or morphological) that are exclusively or predominantly found in either males or females (for example, male lions have manes, females don’t). In contrast, sex differences span a continuum. In other words, while there are average differences between the sexes, males and females may exhibit a range of variations. For example, women typically have more adipose mass, higher circulating free fatty acids, and greater insulin sensitivity in metabolism compared to men. Despite these average differences, when you look at the whole population you can still find individual men that exhibit higher levels of these factors than some women. Similarly, women tend to have a higher resting heart rate and contractility but lower cardiac output than men and generally display stronger immune responses (which may contribute to the higher incidence of diseases such as multiple sclerosis (Català-Senent et al. 2023) and Alzheimer's in women (Casaletto et al. 2022)), but this may not apply to every single individual studied. This difference between a sexual dimorphism and a sex difference is illustrated in Figure 11.8. The image shows the distributions of a trait that shows sexual dimorphism versus a trait that shows a sex difference. Note how the sexual dimorphism distribution is almost completely separate between males and females. The trait with a sex difference, in contrast, shows a difference between the average male and female but the distribution of the observed trait in the two sexes overlaps substantially.

Figure 11.8 Sexual dimorphism versus sex difference

Sex differences are extensive. Indeed, since the inclusion of both sexes in preclinical and clinical studies (see Why Including Sex as a Biological Variable Matters in Biomedical Research), sex differences have been observed in virtually every biological system studied. However, for the scope of this chapter, here we will specifically focus on sex differences in behaviors by exploring examples that are fundamental to everyday functioning and may have significant implications for psychiatric diseases. Later in this chapter, we will delve into the biological mechanisms underlying these sex differences in behavior.

One interesting difference between sexes is associated with sensory perception and processing. For example, compared to men, women tend to show increased sensitivity to smell (Sorokowski et al. 2019), auditory stimuli (Aloufi et al. 2023), and pain (Mogil 2012). This could contribute to women showing higher incidence of chronic pain conditions (Osborne and Davis 2022), and men displaying much greater age-related hearing loss than women do (Pedersen, Rosenhall, and Møller 1989). While the increased sensitivity to sensory stimuli in women may result from psychosocial influences- like gender roles that shape distinct emotional and/or sensory experiences for men and women (Ohla and Lundström 2013; Schroeder 2010)- findings in other animals suggest that at least some of these differences are mediated by biological factors. For instance, compared to their male counterparts, female rodents display heightened pain sensitivity (Ro et al. 2020; Tang et al. 2017) and more acute sense of smell (Baum and Keverne 2002), which could have evolved to meet the distinct demands of each sex's reproductive roles. For example, heightened sensitivity to olfactory and auditory stimuli in females could facilitate maternal behaviors by improving a female's ability to detect and respond to offspring cues as well as predators that pose a threat to vulnerable pups, while males may have evolved reduced pain sensitivity as an adaptation to engage more effectively in physical confrontations with rivals without being incapacitated by injuries, thereby increasing their chances of securing mating opportunities with females. Importantly, these differences in sensory processing could also be linked to differences in perception of stressors and the subsequent physiological and psychological responses in males vs. females.

Sex differences in human behavior extend beyond sensory system effects. For example, how males and females respond to the experience of stress differs on average. Importantly, these sex differences may play a role in the marked disparity in the prevalence of stress-related psychiatric disorders between males and females. We will explore this topic much further in 11.4 Sex Differences in Brain Circuits and Susceptibility to Psychiatric Disease.

In sum, there are important sex differences in the way males vs. females perceive and respond to the world. Many of these differences can be found in non-human animal models, suggesting biological causes. However, as we discussed in the introduction to this chapter, it is crucial to recognize that in humans, gender—defined by the socially transmitted characteristics associated with femininity and masculinity—interacts with biological sex to influence health and disease processes throughout the lifespan (Arcand et al. 2023; Nielsen et al. 2021). This interaction highlights the complexity of human health and underscores the importance of considering both biological sex and gender in medical research and healthcare practices.