# Y chromosome changing sex ratios

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Fisher's principle explains why sex ratios in most sexually reproducing species is approximately $$1:1$$. However, given that in humans and many other animals, males and females differ genetically, it seems that this should cause issues for Fisher's principle.

Say that the Y-chromosome of an animal had a mutation that increased the ratios of males to females produced by the animal. At the extreme, we could imagine a mutation such that the sperm of the animal only carried Y-chromosomes. Although, by the Fisher principle, this would be bad for the overall number of offspring produces by the animal, it seems it would be good for the Y-chromosome itself, since it will now be present in all descendants of the animal (since they are all male), rather than only half the descendants. I would therefore expect that such a mutation would spread, skewing the sex ratios away from $$1:1$$.

Have scenarios like the one I outlined above actually occurred in species? If not, why not?

This sort of thing absolutely happens; useful search terms are "sex ratio distortion", "segregation distortion" (i.e. modifying the ratios with which different chromosomes segregate), and "meiotic drive" (a specific form of segregation distortion).

Your scenario (Y-chromosome genes forcing all offspring to be male) is much less common than the reverse (X-chromosome genes, or other genomic elements, forcing all offspring to be female), because it's easy for an all-female lineage to maintain itself by parthenogenesis. Lyttle (1991) says:

Strong Y drive is of necessity transitory, since drive suppression must either evolve very quickly or the population will be pushed to extinction. This may explain why few Y drive systems have been observed in nature.

However, Lyttle goes on to describe

• W-chromosome drive in butterflies (in butterflies, females are the heterogametic sex - the sex chromosomes are Z and W, ZZ individuals are male and ZW individuals are female). So this is a little bit like your Y-chromosome example, except that the populations end up all-female rather than all-male
• male drive in mosquitoes

Jaenike (2001) says

Although several species exhibit Y drive, X drive is far more common.

Table 1 in that paper lists Y-drive examples in houseflies, mosquitoes, medflies, lemmings, and field mice. (I would include an image, but the table extends over 4 pages… )

I would therefore expect that such a mutation would spread, skewing the sex ratios away from 1:1… Have scenarios like the one I outlined above actually occurred in species? If not, why not?

I haven't dug through all the original literature that Jaenike (2001) cites, to see if there are populations in nature that are male-skewed due to selfish Y chromosomes. The point that Lyttle makes is that, even if you can find evidence of the existence of selfish Y chromosomes hiding in the population, it's very unlikely that these will persist in natural populations for very long, because of the strong selection against them at the population level (and from the rest of the genome); either the population will go extinct, or moderators will evolve that suppress the driving effect of the Y chromosome.

Jaenike, John. “Sex Chromosome Meiotic Drive.” Annual Review of Ecology and Systematics 32, no. 1 (2001): 25-49. https://doi.org/10.1146/annurev.ecolsys.32.081501.113958.

Lyttle, Terrence W. “Segregation Distorters.” Annual Review of Genetics 25, no. 1 (1991): 511-81. https://doi.org/10.1146/annurev.ge.25.120191.002455.

## Sex Chromosome Meiotic Drive

AbstractSex chromosome drive refers to the unequal transmission of X and Y chromosomes from individuals of the heterogametic sex, resulting in biased sex ratios among progeny and within populations. The presence of driving sex chromosomes can reduce mean fitness within a population, bring about intragenomic conflict between the X chromosome, the Y, and the autosomes, and alter the intensity or mode of sexual selection within species. Sex chromosome drive, or its genetic equivalent, is known in plants, mammals, and flies. Many species harboring driving X chromosomes have evolved Y-linked and autosomal suppressors of drive. If a drive polymorphism is not stable, then driving chromosomes may spread to fixation and cause the extinction of a species. Certain characteristics of species, such as population density and female mating rate, may affect the probability of fixation of driving chromosomes. Thus, sex chromosome drive could be an agent of species-level selection.

## Background

The processes of sex determination are tremendously diverse in teleosts and include hermaphroditism and environmental sex determination as well as genetic sex determination [1]. In most cases, the mechanisms of genetic sex determination of teleost fish are quite different from those of tetrapod, even though they originated from the same lineage about 450 million years ago, and share approximately 70% genome sequence similarity [2]. Unlike in mammals and birds, where distinguishable sex chromosomes and common master sex-determining genes are present [3, 4], heterogametic sex chromosomes have only observed in approximately 270 species (less than 1%) of teleost fish of those, approximately 70% are male heterogametic (XX females and XY males) and 30% are female heterogametic (ZZ males and ZW females) [5,6,7].

A wide variety of genetic sex-determining mechanisms have been identified in teleost species, with various genes serving as the “master sex-determining genes” such as DMRT1 in medaka species Oryzias latipes and O. curvinotus [8, 9], GSDF in the medaka species Oryzias luzonensis [10], SDY in rainbow trout (Oncorhynchus mykiss) [11], and AMHY in the Patagonian pejerrey (Odontesthes hatcheri) [12]. In addition to specific sex-determining genes, a single nucleotide polymorphism (SNP) was reported to be responsible for sex determination in fugu (Takifugu rubripes) [13]. Analysis of sex determination patterns in half-smooth tongue sole (Cynoglossus semilaevis) revealed that this species has a ZW type sex determination system, and that the dmrt1 gene exhibited characteristics of sex-determining genes such as sex chromosome linkage, male-specific expression, and essentiality for testis development [14], and that its knockout in ZZ fish (male karyotype) led to the development of female phenotypes [15].

In contrast to highly differentiated sex chromosomes in mammals, where the Y chromosome has lost most of its genes compared to the X chromosome, sex chromosomes of fish species are generally less differentiated. The mammalian Y chromosome has been genetically isolated without recombination with the X chromosome beyond the pseudoautosomal region (PAR) [16, 17], but recombination occurs along the length of the catfish Y and X chromosomes. Significant differences between the W and Z chromosomes have been reported in the female heterogametic half-smooth tongue sole where the W chromosome is more than 8 Mb larger than the Z chromosome. However, sex chromosome karyotypes, and presumably sex chromosome lengths, are highly similar in size in most fish species studied to date [17]. Therefore, even though genetic studies can clearly map the sex determination gene to a chromosomal region, identification of sex determination gene is still a daunting task with teleost fish.

In this study, we adopted an innovative approach for the identification of the sex determination gene in channel catfish by comparative genome analysis of the genomic sequences of the X chromosome and the Y chromosome. Through sex reversal, we were able to produce XY phenotypic females, and mating of XY phenotypic females with the normal XY males allowed the production of offsprings carrying XX, XY, or YY sex chromosome sets. The YY fish offered a unique template for the sequencing and assembly of the sex chromosome sequences. Here, we report the generation of a high-quality whole genome assembly of a YY male fish, comparative genome and transcriptome analyses, and identification of the breast cancer anti-resistance 1 (BCAR1) gene as a candidate for the sex-determining locus in channel catfish.

## Myths of Sex Determination

### Myth 1: Sex is typically determined by X and Y chromosomes

Many biologists are habituated to thinking about sex determination through the familiar examples of mammals and D. melanogaster, and assume that sex determination by sex chromosomes is the norm, that males are XY and females are XX, and that sex chromosomes are a stable component of the genome. While biologists are generally aware of other modes of sex determination (such as female heterogamety in birds, temperature-dependent sex determination in reptiles, or development of males from unfertilized eggs in bees), these alternatives are often viewed as strange and aberrant [8].

### Myth 2: Sex is controlled by one master-switch gene

Sex determination in model species suggests that a master-switch gene (e.g. Sry in mammals, Sxl in D. melanogaster, and xol-1 in C. elegans) acts as the main control element to trigger either male or female sexual development. Changes in the sex determination pathways across taxa are assumed to involve adding a new master-switch gene to this molecular pathway (as in some fly taxa [9]), with little change to downstream elements of the sex determination pathway [10]. A few genes are thought to have the capacity to take on the role of sex determination genes, and these have been co-opted as master-switch genes independently in different lineages (for example, dmrt1 in several vertebrates [11]–[14] and tra in insects [15]–[17]).

### Myth 3: Sex chromosome differentiation and degeneration is inevitable

Sex chromosomes originate from identical autosomes by acquiring a sex determination gene (for example, the origin of the Sry gene in mammals approximately 180 million years ago or Sxl in the Drosophila genus >60 million years ago). They are then thought to differentiate through an inevitable and irreversible process in which recombination between X and Y chromosomes is shut down and the Y degenerates (see Figure 1). Ultimately, Y chromosomes are fated to disappear entirely (“born to be destroyed,” [18]). Thus, sex chromosomes that are morphologically similar (homomorphic) must be evolutionarily young, and in time they too will degenerate.

## Search Scheme and Article Selection

PubMed search engine was used to thoroughly search the MEDLINE database for literature on X and/or Y spermatozoa using the following search terms: ratio, shape, size, gender selection, motility, swimming pattern, velocity, CASA, FISH, flow cytometric analysis, Percoll gradient, albumin gradient, swim-up method, viability, electrophobicity, electronegativity, pH tolerance, surface properties, Y-specific antigen, HY antigen, stress response, oxidative stress, endocrine disruptors, pesticide exposure, environmental toxicants, heat stress, DNA damage, chromosomal abnormality, aneuploidy, XX aneuploidy, XY aneuploidy, YY aneuploidy, proteomics, disease, gender-specific disease, and genomics. Full-text articles and abstracts in English language on X and Y spermatozoa published before December, 2019, were included in the review after screening their content. All article types such as original articles, reviews, letter to the editor, editorials, opinions, and debates were included in the review. Retracted papers were excluded by thoroughly checking the corresponding journal websites.

## 3 RESULTS

### 3.1 Sex assay development

A novel high-throughput assay for the Y chromosome was developed based on the previously identified male-specific MADC6 sequence (Genbank AF364955.1). To develop the assay, the MADC6 sequence was compared to the FINOLA (Genbank GCA_003417725.1) and Purple Kush (Genbank GCA_000230575.1) genomes (Van Bakel et al., 2011 ) using BLAT (BLAST-Like Alignment Tool) on the C. sativa Genome Browser Gateway (UCSC Genome Browser, University of California). A PACE assay, named CSP-1, was designed based on a SNP between the sequences (Figure 2).

### 3.2 Sex assay validation

The CSP-1 assay was used to test a total of 2,170 plants of 14 cultivars. In all but one population the genetic male:female ratio fit the expected 1:1 model (Chi-square p > .05, Table S1). The individuals genetically scored as females were planted in field trials and the individuals genetically scored as males were discarded or moved to greenhouse conditions. Approximately 98% of the screened genetic females were phenotypically female. Approximately 1% of the screened genetic females were monoecious, including individuals from three cultivars (Table S1). Two screened plants were phenotypically male, and when retested, shown to be originally miscalled. About 270 plants genetically scored as male from four hemp cultivars were allowed to flower in greenhouse conditions, and all were phenotypically male (Table 2).

Male plants 14 53 46 157
Female/monoecious plants 21 54 47 157
Marker accuracy 100% 100% 100% 100%
• Lithuanian is a grain type. Nebraska is a grain/fiber type with monoecious individuals. RN16 and RNF are cannabidiol types.

Monoecious plants (20 plants each of the cultivars ‘Anka’, ‘Hlesia’, and ‘USO-31’) were also examined with this assay, and all monoecious plants were scored as female.

### 3.3 Cannabinoid chemotype assay development

A PACE assay to predict cannabinoid chemotype was generated through comparison of marijuana-type CBDAS (BT) and hemp-type CBDAS (BD), which were previously found to correspond to high-THC and high-CBD chemotypes, respectively (Figure 3 Weiblen et al., 2015 ). While THCAS and CBDAS are not the same gene, their close linkage in repulsion suggests that they are inherited monogenically as a cannabinoid chemotype locus (de Meijer et al., 2003 Laverty et al., 2019 ). This assay was named CCP-1.

### 3.4 Cannabinoid chemotype assay validation

Two hundred and seventeen plants from 14 hemp cultivars grown for CBD in two locations were tested with the cannabinoid chemotype (CCP-1) assay and phenotyped for cannabinoids using HPLC. Of these, two were homozygous for the marijuana-type allele (BT/BT), 65 were heterozygous (BT/BD), and 150 were homozygous for the hemp-type allele (BD/BD). Most cultivar populations were segregating for this allele, which was consistent with the phenotypic data (Figure 4). The genotypic data corresponded to three apparent chemotypes, in terms of total potential CBD and THC (Figure 5a, ANOVA p < 1e-4). This indicates that the CCP-1 assay identifies previously established BT and BD alleles (de Meijer et al., 2003 ).

Mean Δ 9 -THC and total potential THC differed across genotypic groups (ANOVA p < 1e-4). Within the genotypic groups there was a strong correlation between total potential CBD and total potential THC concentrations (Figure 5a BT/BD r = .72 p < 1e-4, BD/BD r = .86 p < 1e-4).

The Δ 9 -THC concentration for BD/BD samples was consistently <0.3% (dry weight), while 35% of the BT/BD samples had a Δ 9 -THC concentration <0.3% (Figure 5b). Only 39% of the BD/BD samples had total potential THC concentration <0.3% (Figure 5b). The mean ratio of total potential CBD:THC was 0.02, 1.6, and 20.3 for BT/BT, BT/BD, and BD/BD lines, respectively (Figure 5d Table S2).

A total of 1,420 plants from 47 cultivars were tested with the CCP-1 assay (Table S3). These cultivars were from multiple sources and grown for CBD, grain, or grain/fiber. The THC-associated BT allele frequency varied by cultivar, from 0% in some clones grown for CBD, up to 98% in a Chinese grain/fiber cultivar (Table S3).

### 3.5 Other factors affecting cannabinoid production

Genotypic group, cultivar, and trial were used to create models explaining the potential CBD:THC concentration ratio as well as the concentrations of Δ 9 -THC, CBD, potential THC, potential CBD, and total potential cannabinoids (Table 3). Total potential cannabinoids included CBD, THC, CBC, CBG, and their corresponding acids. Genotypic group explained the most variance in the CBD:THC ratio, as well as Δ 9 -THC and potential THC levels, but not total potential cannabinoids. Cultivar was an important factor in total potential cannabinoid abundance, as well as the concentration of CBD and Δ 9 -THC. The cultivar explained

3% of the variation in the potential CBD:THC ratio when the genotypic group was taken into consideration, and the trial was a poor predictor of all measured variables.

Trial Marker Coding Cultivar Potential CBD:THC Δ 9- THC (%) CBD (%) Potential THC (%) Potential CBD (%) Total Potential Cannabinoids (%)
Model 1 + + + 0.89 0.77 0.21 0.81 0.38 0.19
Model 2 + + 0.86 0.74 0.03 0.78 0.25 0.01
Model 3 + + 0.26 0.23 0.19 0.20 0.18 0.19
Model 4 + 0.01 0.01 0.03 0.00 0.01 0.01
Model 5 + + 0.89 0.76 0.18 0.81 0.38 0.19
Model 6 + 0.86 0.73 0.00 0.77 0.25 0.01
Model 7 + 0.25 0.22 0.16 0.20 0.17 0.18
• ‘+’ indicates the variable was included in the model and ‘‒’ indicates that the variable was not included in the model. Light gray cells are p < .01. Dark gray cells are p < 1e-4.
• Abbreviations: CBD, cannabidiol THC, tetrahydrocannabinol.

## Sex Chromosomes in Pigeons

The way sex determination works in birds is nearly the reverse of how it works in mammals. Sex chromosomes in birds are Z and W. Male birds have two Z chromosomes, and females have a Z, and a W. Male birds make sperm, which always has a Z chromosome. Female gametes (eggs) can have a Z or a W.

• Male offspring get a Z chromosome from each parent
• Females get a Z from their father and a W from their mother
• Z chromosomes don’t pass from mother to daughter
• W chromosomes always pass from mother to daughter

In birds, it’s the males that have two copies of every gene, while the females have just one copy of the genes on the sex chromosomes. The W-chromosome is small, with few genes. But the Z-chromosome has many sex-linked genes, including genes that control feature color and color intensity .

X & Y and Z & W are just two of the ways that sex is determined in animals. Some animals can even change from one sex to another.

## The Y chromosome is disappearing: What will happen to men?

Mole voles have no Y chromosomes. Credit: wikipedia

The Y chromosome may be a symbol of masculinity, but it is becoming increasingly clear that it is anything but strong and enduring. Although it carries the "master switch" gene, SRY, that determines whether an embryo will develop as male (XY) or female (XX), it contains very few other genes and is the only chromosome not necessary for life. Women, after all, manage just fine without one.

What's more, the Y chromosome has degenerated rapidly, leaving females with two perfectly normal X chromosomes, but males with an X and a shriveled Y. If the same rate of degeneration continues, the Y chromosome has just 4.6m years left before it disappears completely. This may sound like a long time, but it isn't when you consider that life has existed on Earth for 3.5 billion years.

The Y chromosome hasn't always been like this. If we rewind the clock to 166m years ago, to the very first mammals, the story was completely different. The early "proto-Y" chromosome was originally the same size as the X chromosome and contained all the same genes. However, Y chromosomes have a fundamental flaw. Unlike all other chromosomes, which we have two copies of in each of our cells, Y chromosomes are only ever present as a single copy, passed from fathers to their sons.

This means that genes on the Y chromosome cannot undergo genetic recombination, the "shuffling" of genes that occurs in each generation which helps to eliminate damaging gene mutations. Deprived of the benefits of recombination, Y chromosomal genes degenerate over time and are eventually lost from the genome.

Despite this, recent research has shown that the Y chromosome has developed some pretty convincing mechanisms to "put the brakes on," slowing the rate of gene loss to a possible standstill.

For example, a recent Danish study, published in PLoS Genetics, sequenced portions of the Y chromosome from 62 different men and found that it is prone to large scale structural rearrangements allowing "gene amplification"—the acquisition of multiple copies of genes that promote healthy sperm function and mitigate gene loss.

The study also showed that the Y chromosome has developed unusual structures called "palindromes" (DNA sequences that read the same forwards as backwards—like the word "kayak"), which protect it from further degradation. They recorded a high rate of "gene conversion events" within the palindromic sequences on the Y chromosome—this is basically a "copy and paste" process that allows damaged genes to be repaired using an undamaged back-up copy as a template.

Looking to other species (Y chromosomes exist in mammals and some other species), a growing body of evidence indicates that Y-chromosome gene amplification is a general principle across the board. These amplified genes play critical roles in sperm production and (at least in rodents) in regulating offspring sex ratio. Writing in Molecular Biology and Evolution recently, researchers give evidence that this increase in gene copy number in mice is a result of natural selection.

Chromosome Y in red, next to the much larger X chromosome. Credit: National Human Genome Research Institute

On the question of whether the Y chromosome will actually disappear, the scientific community, like the UK at the moment, is currently divided into the "leavers" and the "remainers." The latter group argues that its defense mechanisms do a great job and have rescued the Y chromosome. But the leavers say that all they are doing is allowing the Y chromosome to cling on by its fingernails, before eventually dropping off the cliff. The debate therefore continues.

A leading proponent of the leave argument, Jenny Graves from La Trobe University in Australia, claims that, if you take a long-term perspective, the Y chromosomes are inevitably doomed—even if they sometimes hold on a bit longer than expected. In a 2016 paper, she points out that Japanese spiny rats and mole voles have lost their Y chromosomes entirely—and argues that the processes of genes being lost or created on the Y chromosome inevitably lead to fertility problems. This in turn can ultimately drive the formation of entirely new species.

As argued in a chapter in a new e-book, even if the Y chromosome in humans does disappear, it does not necessarily mean that males themselves are on their way out. Even in the species that have actually lost their Y chromosomes completely, males and females are both still necessary for reproduction.

In these cases, the SRY "master switch" gene that determines genetic maleness has moved to a different chromosome, meaning that these species produce males without needing a Y chromosome. However, the new sex-determining chromosome—the one that SRY moves on to—should then start the process of degeneration all over again due to the same lack of recombination that doomed their previous Y chromosome.

The interesting thing about humans is that while the Y chromosome is needed for normal human reproduction, many of the genes it carries are not necessary if you use assisted reproduction techniques. This means that genetic engineering may soon be able to replace the gene function of the Y chromosome, allowing same-sex female couples or infertile men to conceive. However, even if it became possible for everybody to conceive in this way, it seems highly unlikely that fertile humans would just stop reproducing naturally.

Although this is an interesting and hotly debated area of genetic research, there is little need to worry. Scientists don't even know whether the Y chromosome will disappear at all. And, as shown, even if it does, we will most likely continue to need men so that normal reproduction can continue.

Indeed, the prospect of a "farm animal" type system where a few "lucky" males are selected to father the majority of our children is certainly not on the horizon. In any event, there will be far more pressing concerns over the next 4.6m years.

## Think gender comes down to X and Y chromosomes? Think again

This article was published more than 6 years ago. Some information in it may no longer be current.

Peter McKnight is an adjunct professor in the School of Criminology at Simon Fraser University.

So which washroom is Caitlyn Jenner supposed to use? If you haven't been keeping up with the Kardashians, you probably haven't heard that Caitlyn is the name former Olympian and Kardashian patriarch Bruce Jenner has given herself.

And if you haven't been keeping up with transgender issues, you probably haven't heard that these things always come down to washrooms. Those who oppose all matters transgender inevitably get their knickers in a knot about who belongs in which washroom.

Witness the Senate's recent efforts to gut NDP MP Randall Garrison's transgender rights bill by exempting washrooms from its purview. And witness Conservative Senator Donald Plett's comments that "vulnerable women" need to be protected from "biological males" who might enter the women's washroom.

For many people, biology defines sex, and sex is always a binary affair. Sure, postmodernists have been playing with the concept of gender for decades, but sex, well, sex is sacred, which means you're either biologically male or female. But never both. Or neither.

But biology doesn't work that way. Biological phenomena don't necessarily fit into human-ordained binary categories. So while humans insist that you're either male or female – that you have either XY or XX sex chromosomes – biology begs to differ.

For example, genetic men with Klinefelter syndrome possess an extra X chromosome (XXY) or more rarely, two or three extra Xs (XXXY, XXXXY) they typically produce low levels of testosterone, leading to less-developed masculine sexual characteristics and more-developed feminine characteristics than other men. In contrast, some men receive an extra Y chromosome (XYY) in the genetic lottery, and while they have been referred to as "supermales" that is more sensationalism than science.

Genetic women with Turner syndrome have only one X chromosome they often display less-developed female sexual characteristics than other women. And people with a genetic mosaic possess XX chromosomes in some cells and XY in others. So how do we determine if they're male or female? Hint: Don't say that it depends on the chromosomal makeup of the majority of their cells, since women with more than 90 per cent XY genetic material have given birth.

Even if you get the "right" combination of sex chromosomes, it's no guarantee that you'll fit into the carefully circumscribed human definitions of male and female.

For example, genetic women (XX) with congenital adrenal hyperplasia produced unusually high levels of virilizing hormones in utero and develop stereotypically masculine sexual characteristics, including masculinized genitals.

## Comparative Reproduction

### Monotremes, Marsupials and the Origin of SRY

Studies on chromosome evolution in marsupials and monotremes provided important insight into the ancestral sex determination (SD) system of mammals around 180 million years ago, prior to the divergence of the therian mammals ( Wallis et al., 2008 ). Marsupials have a typical XY system, while monotremes display multiple different X and Y sex chromosomes ( Fig. 1 ), which form a chain during meiosis.

Genes from the canonical SD pathway (NR5A1, SOX9, RSPO1 or WNT4…) that were mapped on the platypus genome revealed that they are all located on autosomes ( Grafodatskaya et al., 2007 ) excluding them as legitimate candidates for master sex determining genes. Interestingly, DMRT1, the prime candidate sex determining gene in birds and the avowed master sex determining factor in several frog and fish species ( Table 1 and Fig. 1 ), is located on X-chromosome #5 ( El-Mogharbel et al., 2007 ). This is intriguing, but means that it is present in two copies in females and only one in male. But all what we know so far about DMRT1, from human patients with haploinsufficiency of this gene and from sex determination in birds and several fish, is that double dosage is connected to male development, not female. Currently, the most promising candidate gene, identified by transcriptome analyses, encodes the anti-muellerian hormone (AMH). Further, its position within an ancient bloc of genes on Y-chromosone #5 is consistent with a function as sex-determining gene ( Cortez et al., 2014 ). Validation of this candidate awaits, however, functional characterization.

Marsupials, despite an apparently simpler genetic condition (XY system), with X-chromosomes homologous to a large part (more than 2/3rd) of the eutherian X-chromosomes and the SRY gene present on the Y-chromosome, display, however, major differences in sex differentiation compared to eutherians. Karyotyping of intersex marsupials revealed that a pouch-mammary/scrotum switch gene resides on the X-chromosome ( Sharman et al., 1970 ), pinpointing major genetic rewiring of the complete sex determining gene regulatory network between marsupials and eutherian mammals despite employing the same master sex determiner.

## The birth of a male sex chromosome in Atlantic herring

The evolution of sex chromosomes is of crucial importance in biology as it stabilises the mechanism underlying sex determination and usually results in an equal sex ratio. An international team of scientists, led by researchers from Uppsala University, now reports that they have been able to reconstruct the birth of a male sex chromosome in the Atlantic herring. The male-specific region is tiny and contains only three genes: a sex-determining factor and two genes for sperm proteins. The study is published in PNAS.

It is hard to study the early evolution of sex chromosomes because it usually happened a long time ago and the sex-determining chromosomes usually rapidly degenerate and accumulate repetitive sequences. For instance, humans have an X/Y system of sex determination and the presence of Y determines male sex. The human Y chromosome, which was established more than 100 million years ago, evolved from a chromosome identical to the X chromosome but has since lost most of the genes present on X and is now only about a third the size of the X chromosome. The Atlantic herring also has an X/Y system but it is young and evolved much more recently. In the herring X and Y are almost identical in gene content, the only difference being that Y has three additional genes: a sex-determining factor (BMPR1BBY) and two sperm protein genes predicted to be essential for male fertility.

"The unique feature of this study is that we have been able to reconstruct the birth of a sex chromosome. The evolution of the herring Y chromosome in fact resembles the process when my son makes a construction with pieces of Lego," says Nima Rafati, scientist at Uppsala University and first author on the paper.

Two of the building blocks were formed when extra copies of two different genes emerged and were translocated to what became a male-specific region that cannot exchange genetic material with the X chromosome. This was followed by the incorporation of a third gene to the male-specific region and its loss from the X chromosome.

"The Y-specific gene BMPR1BBY is most certainly the sex-determining factor in Atlantic herring since it belongs to a family of proteins with a critical role in inducing the development of testis. The evolution of BMPR1BBY is a wonderful example of molecular evolution in action. It shows how random mutations and natural selection can 'create' a new gene," says Amaury Herpin, scientist at INRAE, France's new National Research Institute for Agriculture, Food and Environment, and one of the shared first authors.

BMPR1BBY contains about 50 mutations compared with the autosomal copy but it maintains its ability to promote testis development and has evolved an ability to act independently of some of the cofactor the autosomal copy requires. It therefore provides a shortcut to the induction of testis development.

"It has previously been proposed that the presence of a sex-determining factor is not sufficient for the evolution of a sex chromosome, it requires a close association between a sex-determining factor and one or more genes beneficial for that sex," explains Manfred Schartl, professor at Würzburg University and one of the co-authors of the study. "This is exactly what the herring Y chromosome provides, a male-determining factor (BMPR1BBY) and two genes for sperm proteins predicted to be essential for male fertility."

"We are now working on a follow-up study by making an assembly of the sprat genome. Sprat is a close relative to the herring and this analysis will allow us to make a more precise estimate of when this Y chromosome evolved, how stable it is and how rapidly it evolves," says Professor Leif Andersson, Uppsala University, who led the study.

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