How diverse are the sperm cells of an individual male due to random mutations?

How diverse are the sperm cells of an individual male due to random mutations?

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Due to the sheer number of sperm cells in an individual and the rate of mutations, are they likely to be incredibly diverse and encompass most of what we see across our species? For instance would it be likely to find sperm cells that could result in extreme height, intelligence, different skin colour,etc even if the father didn't have any of those genes in their DNA, but a sperm cell did due to mutations?

How diverse are the sperm cells of an individual male due to random mutations? - Biology

Let’s begin with a question: What is a gene mutation and how do mutations occur?

A gene mutation is a permanent alteration in the DNA sequence that makes up a gene, such that the sequence differs from what is found in most people. Mutations range in size they can affect anywhere from a single DNA building block (base pair) to a large segment of a chromosome that includes multiple genes.

Gene mutations can be classified in two major ways:

  • Hereditary mutations are inherited from a parent and are present throughout a person’s life in virtually every cell in the body. These mutations are also called germline mutations because they are present in the parent’s egg or sperm cells, which are also called germ cells. When an egg and a sperm cell unite, the resulting fertilized egg cell receives DNA from both parents. If this DNA has a mutation, the child that grows from the fertilized egg will have the mutation in each of his or her cells.
  • Acquired (or somatic) mutations occur at some time during a person’s life and are present only in certain cells, not in every cell in the body. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation.

Genetic changes that are described as de novo (new) mutations can be either hereditary or somatic. In some cases, the mutation occurs in a person’s egg or sperm cell but is not present in any of the person’s other cells. In other cases, the mutation occurs in the fertilized egg shortly after the egg and sperm cells unite. (It is often impossible to tell exactly when a de novo mutation happened.) As the fertilized egg divides, each resulting cell in the growing embryo will have the mutation. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell in the body but the parents do not, and there is no family history of the disorder.

Somatic mutations that happen in a single cell early in embryonic development can lead to a situation called mosaicism. These genetic changes are not present in a parent’s egg or sperm cells, or in the fertilized egg, but happen a bit later when the embryo includes several cells. As all the cells divide during growth and development, cells that arise from the cell with the altered gene will have the mutation, while other cells will not. Depending on the mutation and how many cells are affected, mosaicism may or may not cause health problems.

Most disease-causing gene mutations are uncommon in the general population. However, other genetic changes occur more frequently. Genetic alterations that occur in more than 1 percent of the population are called polymorphisms. They are common enough to be considered a normal variation in the DNA. Polymorphisms are responsible for many of the normal differences between people such as eye color, hair color, and blood type. Although many polymorphisms have no negative effects on a person’s health, some of these variations may influence the risk of developing certain disorders.

Process of Meiosis

A man produces sperm and a woman produces eggs because their reproductive cells undergo meiosis. Meiosis starts with one cell that has the full number of chromosomes specific to each organism -- human cells have 46 chromosomes. It ends with four cells, called gametes, that each have half the full number of chromosomes. Meiosis is a multi-step process in which a cell makes a copy of each strand of DNA, called a chromosome, and then divides twice. Each time it divides, it cuts its DNA content in half. In humans, a cell goes from having 46 strands of DNA, and then 96 after each is copied. The first division of meiosis cuts 96 in half into 46. The second division cuts 46 into 23, which is the number of chromosomes in a sperm or an egg.

Crossing Over

During prophase of meiosis I, the double-chromatid homologous pairs of chromosomes cross over with each other and often exchange chromosome segments. This recombination creates genetic diversity by allowing genes from each parent to intermix, resulting in chromosomes with a different genetic complement. The exchange occurs between non-sister chromatids. Because genes often interact with each other, the new combination of genes on a chromosome can lead to new traits in offspring.


Mate-guarding is a defensive behavioral trait that occurs in response to sperm competition males try to prevent other males from approaching the female (and/or vice versa) thus preventing their mate from engaging in further copulations. [2] Precopulatory and postcopulatory mate-guarding occurs in birds, lizards, insects and primates. Mate-guarding also exists in the fish species Neolamprologus pulcher, as some males try to "sneak" matings with females in the territory of other males. In these instances, the males guard their female by keeping them in close enough proximity so that if an opponent male shows up in his territory he will be able to fight off the rival male which will prevent the female from engaging in extra-pair copulation with the rival male. [9]

Organisms with polygynous mating systems are controlled by one dominant male. In this type of mating system, the male is able to mate with more than one female in a community. [10] The dominant males will reign over the community until another suitor steps up and overthrows him. [10] The current dominant male will defend his title as the dominant male and he will also be defending the females he mates with and the offspring he sires. The elephant seal falls into this category since he can participate in bloody violent matches in order to protect his community and defend his title as the alpha male. [11] If the alpha male is somehow overthrown by the newcomer, his children will most likely be killed and the new alpha male will start over with the females in the group so that his lineage can be passed on. [12]

Strategic mate-guarding occurs when the male only guards the female during her fertile periods. This strategy can be more effective because it may allow the male to engage in both extra-pair paternity and within-pair paternity. [13] This is also because it is energetically efficient for the male to guard his mate at this time. There is a lot of energy that is expended when a male is guarding his mate. For instance, in polygynous mate-guarding systems, the energetic costs of males is defending their title as alpha male of their community. [11] Fighting is very costly in regards to the amount of energy used to guard their mate. These bouts can happen more than once which takes a toll on the physical well-being of the male. Another cost of mate-guarding in this type of mating system is the potential increase of the spread of disease. [14] If one male has an STD, he can pass that on to the females that he's copulating with, potentially resulting in a depletion of the harem. This would be an energetic cost towards both genders for the reason that instead of using the energy for reproduction, they are redirecting it towards ridding themselves of this illness. Some females also benefit from polygyny because extra pair copulations in females increase the genetic diversity with the community of that species. [15] This occurs because the male is not able to watch over all of the females and some will become promiscuous. Eventually, the male will not have proper nutrition, which makes the male unable to produce sperm. [16] For instance, male amphipods will deplete their reserves of glycogen and triglycerides only to have it replenished after the male is done guarding that mate. [17] Also, if the amount of energy intake does not equal the energy expended, then this could be potentially fatal to the male. Males may even have to travel long distances during the breeding season in order to find a female which absolutely drain their energy supply. Studies were conducted to compare the cost of foraging of fish that migrate and animals that are residential. The studies concluded that fish that were residential had fuller stomachs containing higher quality of prey compared to their migrant counterparts. [18] With all of these energy costs that go along with guarding a mate, timing is crucial so that the male can use the minimal amount of energy. This is why it is more efficient for males to choose a mate during their fertile periods. [13] Also, males will be more likely to guard their mate when there is a high density of males in the proximity. [2] Sometimes, organisms put in all this time and planning into courting a mate in order to copulate and she may not even be interested. There is a risk of cuckoldry of some sort, since a rival male can successfully court the female that the male originally courting her could not do. [19]

However, there are benefits that are associated with mate-guarding. In a mating- guarding system, both parties, male and female, are able to directly and indirectly benefit from this. For instance, females can indirectly benefit from being protected by a mate. [20] The females can appreciate a decrease in predation and harassment from other males while being able to observe her male counterpart. [20] This will allow her to recognize particular traits that she finds ideal so that she'll be able to find another male that emulates those qualities. In polygynous relationships, the dominant male of the community benefits because he has the best fertilization success. [12] Communities can include 30 up to 100 females and, compared to the other males, will greatly increase his chances of mating success. [11]

Males who have successfully courted a potential mate will attempt to keep them out of sight of other males before copulation. One way organisms accomplish this is to move the female to a new location. Certain butterflies, after enticing the female, will pick her up and fly her away from the vicinity of potential males. [21] In other insects, the males will release a pheromone in order to make their mate unattractive to other males or the pheromone masks her scent completely. [21] Certain crickets will participate in a loud courtship until the female accepts his gesture and then it suddenly becomes silent. [22] Some insects, prior to mating, will assume tandem positions to their mate or position themselves in a way to prevent other males from attempting to mate with that female. [21] The male checkerspot butterfly has developed a clever method in order to attract and guard a mate. He will situate himself near an area that possesses valuable resources that the female needs. He will then drive away any males that come near and this will greatly increase his chances of copulation with any female that comes to that area. [23]

In post-copulatory mate-guarding males are trying to prevent other males from mating with the female that they have mated with already. For example, male millipedes in Costa Rica will ride on the back of their mate letting the other males know that she's taken. [24] Japanese beetles will assume a tandem position to the female after copulation. [25] This can last up to several hours allowing him to ward off any rival males giving his sperm a high chance to fertilize that female's egg. These, and other, types of methods have the male playing defense by protecting his mate. Elephant seals are known to engage in bloody battles in order to retain their title has dominant male so that they are able to mate with all the females in their community. [11]

Copulatory plugs are frequently observed in insects, reptiles, some mammals, and spiders. [2] Copulatory plugs are inserted immediately after a male copulates with a female, which reduce the possibility of fertilization by subsequent copulations from another male, by physically blocking the transfer of sperm. [2] Bumblebee mating plugs, in addition to providing a physical barrier to further copulations, contain linoleic acid, which reduces re-mating tendencies of females. [26] A species of Sonoran desert Drosophila, Drosophila mettleri, uses copulatory plugs to enable males to control the sperm reserve space females have available. This behavior ensures males with higher mating success at the expense of female control of sperm (sperm selection).

Similarly, Drosophila melanogaster males release toxic seminal fluids, known as ACPs (accessory gland proteins), from their accessory glands to impede the female from participating in future copulations. [27] These substances act as an anti-aphrodisiac causing a dejection of subsequent copulations, and also stimulate ovulation and oogenesis. [5] Seminal proteins can have a strong influence on reproduction, sufficient to manipulate female behavior and physiology. [28]

Another strategy, known as sperm partitioning, occurs when males conserve their limited supply of sperm by reducing the quantity of sperm ejected. [2] In Drosophila, ejaculation amount during sequential copulations is reduced this results in half filled female sperm reserves following a single copulatory event, but allows the male to mate with a larger number of females without exhausting his supply of sperm. [2] To facilitate sperm partitioning, some males have developed complex ways to store and deliver their sperm. [29] In the blue headed wrasse, Thalassoma bifasciatum, the sperm duct is sectioned into several small chambers that are surrounded by a muscle that allows the male to regulate how much sperm is released in one copulatory event. [30]

A strategy common among insects is for males to participate in prolonged copulations. By engaging in prolonged copulations, a male has an increased opportunity to place more sperm within the female's reproductive tract and prevent the female from copulating with other males. [31]

It has been found that some male mollies (Poecilia) have developed deceptive social cues to combat sperm competition. Focal males will direct sexual attention toward typically non-preferred females when an audience of other males is present. This encourages the males that are watching to attempt to mate with the non-preferred female. This is done in an attempt to decrease mating attempts with the female that the focal male prefers, hence decreasing sperm competition. [32]

Offensive adaptation behavior differs from defensive behavior because it involves an attempt to ruin the chances of another male's opportunity in succeeding in copulation by engaging in an act that tries to terminate the fertilization success of the previous male. [5] This offensive behavior is facilitated by the presence of certain traits, which are called armaments. [33] An example of an armament are antlers. Further, the presence of an offensive trait sometimes serves as a status signal. The mere display of an armament can suffice to drive away the competition without engaging in a fight, hence saving energy. [33] A male on the offensive side of mate-guarding may terminate the guarding male's chances at a successful insemination by brawling with the guarding male to gain access to the female. [2] In Drosophila, males release seminal fluids that contain additional toxins like pheromones and modified enzymes that are secreted by their accessory glands intended to destroy the sperm that have already made their way into the female's reproductive tract from a recent copulation. [5] Based on the "last male precedence" idea, some males can remove sperm from previous males by ejaculating new sperm into the female hindering successful insemination opportunities of the previous male. [34]

The "good sperm hypothesis" is very common in polyandrous mating systems. [35] The "good sperm hypothesis" suggests that a male's genetic makeup will determine the level of his competitiveness in sperm competition. [35] When a male has "good sperm" he is able to father more viable offspring than males that do not have the "good sperm" genes. [35] Females may select males that have these superior "good sperm" genes because it means that their offspring will be more viable and will inherit the "good sperm" genes which will increase their fitness levels when their sperm competes. [36]

Studies show that there is more to determining the competitiveness of the sperm in sperm competition in addition to a male's genetic makeup. A male's dietary intake will also affect sperm competition. An adequate diet consisting of increased amounts of diet and sometimes more specific ratio in certain species will optimize sperm number and fertility. Amounts of protein and carbohydrate intake were tested for its effects on sperm production and quality in adult fruit flies (Diptera: Tephritidae). Studies showed these flies need to constantly ingest carbohydrates and water to survive, but protein is also required to attain sexual maturity. [37] In addition, The Mediterranean fruit fly, male diet has been shown to affect male mating success, copula duration, sperm transfer, and male participation in leks. [38] These all require a good diet with nutrients for proper gamete production as well as energy for activities, which includes participation in leks.

In addition, protein and carbohydrate amounts were shown to have an effect on sperm production and fertility in the speckled cockroach. Holidic diets were used which allowed for specific protein and carbohydrate measurements to be taken, giving it credibility. A direct correlation was seen in sperm number and overall of food intake. More specifically, optimal sperm production was measured at a 1:2 protein to carbohydrate ratio. Sperm fertility was best at a similar protein to carbohydrate ratio of 1:2. This close alignment largely factors in determining male fertility in Nauphoeta cinerea. [39] Surprisingly, sperm viability was not affected by any change in diet or diet ratios. It's hypothesized that sperm viability is more affected by the genetic makeup, like in the "good sperm hypothesis". These ratios and results are not consistent with many other species and even conflict with some. It seems there can't be any conclusions on what type of diet is needed to positively influence sperm competition but rather understand that different diets do play a role in determining sperm competition in mate choice.

One evolutionary response to sperm competition is the variety in penis morphology of many species. [40] [41] For example, the shape of the human penis may have been selectively shaped by sperm competition. [42] The human penis may have been selected to displace seminal fluids implanted in the female reproductive tract by a rival male. [42] Specifically, the shape of the coronal ridge may promote displacement of seminal fluid from a previous mating [43] via thrusting action during sexual intercourse. [42] A 2003 study by Gordon G. Gallup and colleagues concluded that one evolutionary purpose of the thrusting motion characteristic of intense intercourse is for the penis to “upsuck” another man's semen before depositing its own. [44]

Evolution to increase ejaculate volume in the presence of sperm competition has a consequence on testis size. Large testes can produce more sperm required for larger ejaculates, and can be found across the animal kingdom when sperm competition occurs. [45] Males with larger testes have been documented to achieve higher reproductive success rates than males with smaller testes in male yellow pine chipmunks. [45] In chichlid fish, it has been found that increased sperm competition can lead to evolved larger sperm numbers, sperm cell sizes, and sperm swimming speeds. [46]

In some insects and spiders, for instance Nephila fenestrate, the male copulatory organ breaks off or tears off at the end of copulation and remains within the female to serve as a copulatory plug. [47] This broken genitalia is believed to be an evolutionary response to sperm competition. [47] This damage to the male genitalia means that these males can only mate once. [48]

Female factors can influence the result of sperm competition through a process known as "sperm choice". [49] Proteins present in the female reproductive tract or on the surface of the ovum may influence which sperm succeeds in fertilizing the egg. [49] During sperm choice, females are able to discriminate and differentially use the sperm from different males. One instance where this is known to occur is inbreeding females will preferentially use the sperm from a more distantly related male than a close relative. [49]

Post-copulatory inbreeding avoidance Edit

Inbreeding ordinarily has negative fitness consequences (inbreeding depression), and as a result species have evolved mechanisms to avoid inbreeding. Inbreeding depression is considered to be due largely to the expression of homozygous deleterious recessive mutations. [50] Outcrossing between unrelated individuals ordinarily leads to the masking of deleterious recessive mutations in progeny. [51]

Numerous inbreeding avoidance mechanisms operating prior to mating have been described. However, inbreeding avoidance mechanisms that operate subsequent to copulation are less well known. In guppies, a post-copulatory mechanism of inbreeding avoidance occurs based on competition between sperm of rival males for achieving fertilization. [52] In competitions between sperm from an unrelated male and from a full sibling male, a significant bias in paternity towards the unrelated male was observed. [52]

In vitro fertilization experiments in the mouse, provided evidence of sperm selection at the gametic level. [53] When sperm of sibling and non-sibling males were mixed, a fertilization bias towards the sperm of the non-sibling males was observed. The results were interpreted as egg-driven sperm selection against related sperm.

Female fruit flies (Drosophila melanogaster) were mated with males of four different degrees of genetic relatedness in competition experiments. [54] Sperm competitive ability was negatively correlated with relatedness.

Female crickets (Teleogryllus oceanicus) appear to use post-copulatory mechanisms to avoid producing inbred offspring. When mated to both a sibling and an unrelated male, females bias paternity towards the unrelated male. [55]

It has been found that because of female choice (see sexual selection), morphology of sperm in many species occurs in many variations to accommodate or combat (see sexual conflict) the morphology and physiology of the female reproductive tract. [56] [57] [58] However, it is difficult to understand the interplay between female and male reproductive shape and structure that occurs within the female reproductive tract after mating that allows for the competition of sperm. Polyandrous females mate with many male partners. [59] Females of many species of arthropod, mollusk and other phyla have a specialized sperm-storage organ called the spermatheca in which the sperm of different males sometimes compete for increased reproductive success. [57] Species of crickets, specifically Gryllus bimaculatus, are known to exhibit polyandrous sexual selection. Males will invest more in ejaculation when competitors are in the immediate environment of the female.

Evidence exists that illustrates the ability of genetically similar spermatozoa to cooperate so as to ensure the survival of their counterparts thereby ensuring the implementation of their genotypes towards fertilization. Cooperation confers a competitive advantage by several means, some of these include incapacitation of other competing sperm and aggregation of genetically similar spermatozoa into structures that promote effective navigation of the female reproductive tract and hence improve fertilization ability. Such characteristics lead to morphological adaptations that suit the purposes of cooperative methods during competition. For example, spermatozoa possessed by the wood mouse (Apodemus sylvaticus) possess an apical hook which is used to attach to other spermatozoa to form mobile trains that enhance motility through the female reproductive tract. [60] Spermatozoa that fail to incorporate themselves into mobile trains are less likely to engage in fertilization. Other evidence suggests no link between sperm competition and sperm hook morphology. [61]

Selection to produce more sperm can also select for the evolution of larger testes. Relationships across species between the frequency of multiple mating by females and male testis size are well documented across many groups of animals. For example, among primates, female gorillas are relatively monogamous, so gorillas have smaller testes than humans, which in turn have smaller testes than the highly promiscuous bonobos. [62] Male chimpanzees that live in a structured multi-male, multi-female community, have large testicles to produce more sperm, therefore giving him better odds to fertilize the female. Whereas the community of gorillas consist of one alpha male and two or three females, when the female gorillas are ready to mate, normally only the alpha male is their partner.

Regarding sexual dimorphism among primates, humans falls into an intermediate group with moderate sex differences in body size but relatively large testes. This is a typical pattern of primates where several males and females live together in a group and the male faces an intermediate number of challenges from other males compared to exclusive polygyny and monogamy but frequent sperm competition. [63]

Other means of sperm competition could include improving the sperm itself or its packaging materials (spermatophore). [64]

The male black-winged damselfly provides a striking example of an adaptation to sperm competition. Female black-winged damselflies are known to mate with several males over the span of only a few hours and therefore possess a receptacle known as a spermatheca which stores the sperm. During the process of mating the male damselfly will pump his abdomen up and down using his specially adapted penis which acts as a scrub brush to remove the sperm of another male. This method proves quite successful and the male damselfly has been known to remove 90-100 percent of the competing sperm. [65]

A similar strategy has been observed in the dunnock, a small bird. Before mating with the polyandrous female, the male dunnock pecks at the female's cloaca in order to peck out the sperm of the previous male suitor. [66]

In the fly Dryomyza anilis, females mate with multiple males. It benefits the male to attempt to be the last one to mate with a given female. [67] This is because there seems to be a cumulative percentage increase in fertilization for the final male, such that the eggs laid in the last oviposition bout are the most successful.


Here, we surveyed recent discoveries of pollen and stigma functions, including (1) pollen adhesion, a multiphase process that is initially independent of protein–protein interactions but later involves pollen coat proteins (2) pollen hydration, a step for which the presence of lipids, whether provided by the male or the female surface, likely modulates water transport while diverse proteins mediate pollen incompatibility (3) pollen activation and germination, processes dependent on polarizing cues, cytoplasmic rearrangements, and the harnessing of biomechanical forces for the focused breaching of the exine wall and (4) stigma invasion, a stage that involves the localized activity of digestive enzymes. We also addressed the great diversity in pollen and stigma structures used across taxa to accomplish pollination, including diversity in pollen wall development, pollen delivery, pollen coat composition, and stigma development.

Studies of model organisms have revealed key molecules and mechanisms, setting the stage for comparative studies across taxa. For example, in pollen wall development, the patterning genes identified through Arabidopsis screens are likely to be highly variable between species, either in their coding sequences or in the sites and timing of their expression. Work in comparative genomics is called for not only within the angiosperms but between pollen, fern spores, and even diatoms ( Schmid et al., 1996), in which similar cytoskeletal and plasma membrane shifts are likely associated with wall construction, sculpting, and aperture placement. Because genes that play roles in determining wall morphologies are the very genes altered through evolution, patterns considered aberrant or mutant to one species may be considered normal in another. Suppositions such as that sculpted exine is required to hold an abundant pollen coat could be addressed using Arabidopsis mutations, such as lap1 ( Zinkl and Preuss, 2000), that affect exine patterning. The roles of pollen coat or pollen dispersal unit size in pollinator preference and pollen delivery could be addressed using knowledge of Arabidopsis mutants, such as those in ECERIFERUM, TES/STUD, or QUARTET genes (the former affects pollen coat quantity and the latter two affect the release of monad pollen, respectively). Comparative genomics and RNA interference technology then could be exploited to knock out these genes in insect-pollinated flowers, such as those of Brassica. Integrating cell, genetic, and genomic studies of model organisms with comparative studies of relationship and evolution allows pollen and stigma sophistication to be viewed in the context of coadaptive or mutual evolutionary adjustments. Because pollination mechanisms also are key to reproductive isolation and speciation, attention focused across a variety of species also will help to complete any model of the success and diversity of angiosperms.

Drosophila and Lepidoptera

All investigated species of Drosophila are male-heterogametic, and while there have been fusions, Drosophila species that have been studied share at least one large homologous sex-linked region (Muller Element A Schaeffer et al. 2008). Diversity in Drosophila has been used to study population structure, introgression, natural selection, and sex-biased processes. Perhaps, one of the most important lessons from diversity on the sex chromosomes in Drosophila is on the importance of genetic drift. Genetic diversity (measured using both π and s) across four loci on the X chromosome and two mtDNA loci in wild caught Drosophilapseudoobscura and Drosophilapersimilis populations with samples taken 16 years apart (sampled in 1997 and in 2003) was not significantly different in either population, but Tajima’s D was very different for one locus, reiterating that genetic drift over time can affect estimates of Tajima’s D ( Gredler et al. 2015).

An analysis of genetic diversity across the X chromosome and autosomes in an African population of Drosophilamelanogaster (chosen because it was not expected to exhibit the extreme bottlenecks of non-African populations) confirmed that diversity is lower in regions with low rates of recombination, and that the efficacy of selection correlates positively with the rate of recombination ( Campos et al. 2014). The X chromosome in African D. melanogaster shows a pattern consistent with increased adaptive evolution on the X chromosome ( Campos et al. 2014), also called a fast-X effect ( Meisel and Connallon 2013 Box 1). Similarly, the X chromosome is routinely underenriched for regions involved in admixture across Drosophila species ( Herrig et al. 2014), which could occur if the X chromosome harbors alleles with negative epistatic effects ( Pool et al. 2012), also referred to as the large-X effect (Box 1). A comparison of X-linked and autosomal divergence between Drosophilamauritiana and Drosophilasechellia, and diversity across the genome of D. mauritiana, also reported that X-linked divergence is increased relative to autosomal divergence, but X-linked diversity is much lower, consistent with selective sweeps acting in the X as these two populations diverged about 240,000 years ago ( Garrigan et al. 2014).

Overall, putatively neutral diversity on the X chromosome (which should not be subject to the Fast-X effect) relative to diversity on the autosomes is still lower than 0.75 in many species and subpopulations of Drosophila (e.g., D. subobscura [ Herrig et al. 2014], D. simulans [ Begun et al. 2007], D. pseudoobscura and D. miranda [ Haddrill et al. 2010], and non-African populations of D. melanogaster [ Andolfatto 2001]). Some species of Drosophila, like D. madeirensis ( Herrig et al. 2014), exhibit an X/A diversity ratio that is not significantly different from 0.75, and, curiously, African populations of D. melanogaster have typically been found to exhibit an X/A diversity ratio greater than 0.75 ( Andolfatto 2001 Langley et al. 2012 Singh et al. 2013). But, before definite conclusions can be drawn about what these ratios mean, linked selection, and its effects on diversity, must be taken into account. Analysis of X-linked and autosomal diversity far from genes in African and non-African populations of D. melanogaster did not find the striking differences in X/A diversity as previous studies, but still concluded that both population demography and selection together shape the ratio of X/A diversity ( Singh et al. 2007).

The ratio of diversity on the Y chromosome relative to the autosomes should be about 0.25, under neutral demographic scenarios, but similar to the Y in mammals and the W in birds, Y-linked diversity across Drosophila populations is routinely much lower than neutral expectations. Y chromosome diversity is exceedingly low across all D. melanogaster populations studied, some of which can be explained by population demography, but not in African populations, where recent selective sweeps are proposed to explain the low Y-linked diversity in populations from Zimbambwe and Uganda ( Larracuente and Clark 2013). Diversity is also reported to be much lower than neutral expectations in D. subobscura and D. madeirensis and is inferred to be due to linked selection—either background selection or hitchhiking—because corresponding X/A ratios in these species are not consistent with extreme variance in male reproductive success ( Herrig et al. 2014). In contrast, a study of Y-linked diversity in D. simulans reported only a single polymorphism in ten lines ( Zurovcova and Eanes 1999), but the authors ruled out background selection because of the limited number of genes on the D. simulans Y chromosome further investigations are needed to determine whether this low Y variation in D. simulans is due primarily to selection or extreme variance in male reproductive success.

Patterns of low Y-linked diversity can also extend to neo-Y chromosomes (a neo-sex chromosome is an old sex chromosome to which an autosome has recently been fused). Genetic diversity is reduced on the neo-Y chromosome in D. miranda relative to the neo-X chromosome at single nucleotide markers ( Yi and Charlesworth 2000) and microsatellite loci ( Bachtrog and Charlesworth 2000) relative to neo-X loci. In contrast, analyses of the genetic diversity on the neo-Y chromosome in D. albomicans did not find low Y-linked diversity ( Satomura and Tamura 2016). It is possible that the results of these studies may be reconciled by considering the effects of time since total recombination suppression on the Y chromosome (the neo-Y in D. albomicans is about 0.5 Myr old [ Lin et al. 2008], whereas the D. miranda neo-Y is approximately double that age, at about 1 Myr old [ Bachtrog and Charlesworth 2002]), or there may be unique species-specific demography that affected sex-linked diversity differently in these species.

Understanding variation on the Y chromosome is also important for comprehensive characterization of genome-wide variation. Natural variation on the Y chromosome in D. melanogaster is significantly associated with change in expression for 2.84% of non-Y-linked genes ( Sackton et al. 2011), especially genes involved in the immune system and in detecting pheromones ( Jiang et al. 2010). There is also evidence that variation on the Y chromosome in Drosophila preferentially regulates tissue-specific genes and genes in repressive chromatin ( Sackton and Hartl 2013).

Genetic diversity in butterflies and moths has not yet been used to test many theoretical predictions, but, because moths and butterflies (together called Lepidoptera) have a ZZ/ZW female-heterogametic sex determination system ( Kaiser and Bachtrog 2010), they make an excellent comparison group to the XX/XY Drosophila and mosquitos. Largely, sex-linked genetic diversity in Lepidoptera has been studied to test for evidence of speciation and species interbreeding. High levels of shared genetic diversity across five loci on the Z chromosome in two species of Swallowtail butterfly species (Papilio canadensis and Papilioglaucus) were used to reject a model of allopatric speciation between them ( Putnam et al. 2007). Similarly, autosomal variation across 31 Heliconius butterflies (H. melpomene, H. cydno, and H. timareta) suggests sympatric speciation with routine admixture between species, but Z-linked loci show significantly reduced levels of admixture relative to the autosomes ( Martin et al. 2013). This is consistent with the large-Z effect that alleles involved in inter-species genetic incompatibility accumulate faster on the Z chromosome than on the autosomes (Box 1). The large-Z is expected to occur either as the result of more genetic drift on the Z relative to the autosomes or when positive selection fixes unique alleles between species on the Z faster than on the autosomes. Consistent with the latter, patterns of genetic diversity suggest a stronger signal of positive selection on the silkmoth Z chromosome relative to the autosomes (a fast-Z effect Box 1) ( Sackton et al. 2014). However, hemizygosity can result in several evolutionary differences between the sex chromosomes and the autosomes in contrast to strong positive selection, low rates of evolution and diversity suggest that purifying selection is stronger on the Z than the autosomes in two satyrine butterflies ( Rousselle et al. 2016).

W-linked loci have not yet been studied extensively across Lepidoptera. Unlike the shared ancestry of the Y in mammals, or homologous W chromosomes across birds, the W chromosomes of Lepidoptera show evidence of frequent turnover ( Sahara et al. 2012), which may limit future analyses if sequencing of a reference chromosome is required. Similar to other W and Y chromosomes, Lepidoptera W chromosomes are extremely repeat-rich ( Abe et al. 2005), which is a challenge for chromosome assembly and estimates of diversity across species. But, W-linked markers from silkworm are also female-specific in the sugar cane borer ( Heideman et al. 2010), suggesting that at least some regions of this W chromosome are conserved enough to facilitate future studies of genetic diversity.

Diversity, severity of autism symptoms linked to mutation locations

Credit: CC0 Public Domain

One of the most recognizable characteristics of autism is an amazing diversity of associated behavioral symptoms. Clinicians view autism as a broad spectrum of related disorders, and the origin of the disease's heterogeneity has puzzled scientists, doctors, and affected families for decades.

In a recent study, researchers at Columbia University Vagelos College of Physicians and Surgeons have made an important step towards understanding the biological mechanisms underlying the cognitive and behavioral diversity of autism cases triggered by de novo truncating mutations. These mutations occur in parents' germline cells and usually strongly disrupt the functions of target genes. De novo truncating mutations are responsible for close to 5% of autism cases and up to 20% of cases seen clinically.

Autism spectrum disorders that are triggered by a single disrupted gene represent a relatively simple genetic type of the disease. The perplexing observation that scientists were grappling with for many years is that even when truncating mutations occur in the same gene, they often lead to a wide range of symptoms and behavioral patterns in different children.

The new study found that the severity of autism symptoms often depends on which specific functional unit within a gene is the target of a mutation.

"It turns out that we weren't looking closely enough at how and where an autism gene is mutated," says study leader Dennis Vitkup, Ph.D., associate professor of systems biology and of biomedical informatics at Columbia University Vagelos College of Physicians.

Human genes, similar to genes of other eukaryotic species, are composed of separate coding units, called exons, which are frequently joined together in different combinations across tissues and developmental stages. "Upon closer examination, we found that different children with truncating mutations in the same exon have strikingly similar behavioral symptoms and disabilities," Vitkup says.

The study was published online in the journal Molecular Psychiatry.

Same exon, similar symptoms

In the study, Vitkup and colleagues Andrew H. Chiang, Jonathan Chang, and Jiayao Wang analyzed genetic and clinical data from over 2,500 people with autism, focusing on cases resulting from truncating mutations.

When the researchers compared random pairs of children with autism, they found that their nonverbal, verbal, and overall IQ scores differed on average by more than 30 points. Children with truncating mutations in the same gene showed similar differences.

However, when the researchers compared autistic children affected by mutations in the same exon of the same gene, their IQs differed by less than ten points, which is comparable to the IQ measurement errors. The researchers observed very similar patterns for multiple other scores characterizing children's communication, social, and motors skills.

"This tells us that, with autism-associated truncating mutations, it's the exon, and not the whole gene, that often represents a functional unit of impact," Vitkup says.

More severe symptoms associated with frequently used exons

The researchers demonstrated that the behavioral and cognitive severity of autism is proportional to the likelihood with which targeted exons are used in gene transcripts, with more severe effects associated with mutations in more frequently used exons. When mutations occur in the same exon, the resulting expression-level changes are especially similar, leading to similar clinical consequences.

Surprisingly, the study also showed that the gene expression changes caused by truncating mutations can be quite mild. "Our analysis demonstrates that autism cases can be triggered by relatively small changes in overall gene dosage, often as small as 15%," says the study's first author Andrew Chiang, a graduate student in the Department of Biomedical Informatics.

Implications for precision medicine

The study may have significant implications for precision medicine. Diagnostic and prognostic tests may now pay special attention to specific exons affected by truncating mutations.

The study also suggests a therapeutic approach for alleviating the consequences of truncating mutations in autism. "It would be very hard to develop drugs for thousands of different mutations in many hundreds of target autism genes," Vitkup says, "but our study demonstrates that behavioral abnormalities often originate from relatively small decreases in the target gene's dosage. These genetic insults may be, at least partially, compensated by increasing the expression of an unaffected gene copy using new molecular tools such as CRISPR."


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Conclusions and outlook

In this brief survey we have attempted to highlight how thinking about the selective pressures acting on spermatogenesis can be a useful framework for understanding how this important process is organized, and for explaining interspecific (and probably intraspecific) diversity in its details. In particular, although not often considered in the biomedical literature, we have demonstrated that sperm competition is a pervasive and influential evolutionary force acting on male reproductive biology, and a relevant factor for explaining multiple aspects of sperm production. As we have illustrated, these include some of the most important outstanding gaps in our knowledge about spermatogenesis, such as why different species vary so much in such basic features as the number and type of sperm produced, and in the stem cell systems that support this process. We suggest that fusing the proximate and ultimate outlooks traditionally adopted by reproductive and evolutionary biologists, respectively, holds great potential for further advancing our understanding of spermatogenesis, and hope that our review might help stimulate greater dialogue between researchers in these two traditionally quite separate fields. We see some cause for optimism on this front, in part enabled by vastly improved access to genetic and genomic data through next-generation sequencing and associated technologies, and by the increasing application of molecular techniques that were once the preserve of a small number of traditional model systems to a broader range of species. This breadth will often be needed to test particular evolutionary hypotheses derived from a ‘sperm competition perspective’.

Watch the video: 9 Months In The Womb: A Remarkable Look At Fetal Development Through Ultrasound By (August 2022).