With Father’s Day around the corner, we’re raising a glass in honor of the dads, granddads, and father figures who show up with heart, humor, and a helping hand. While there are plenty of ways to be a father outside of genetics, it feels like the perfect moment to spotlight one of the most curiously underexplored characters in the genome: the Y chromosome, which, like many of the dads we know and love, is full of surprises.
Today’s blog is a masterclass on sex chromosomes from Senior Scientist Sarah Carey in Alex Harkess’s lab at HudsonAlpha Institute for Biotechnology, a non-profit genetics and genomics research institute in Huntsville, Alabama and Ellie Armstrong, an Assistant Professor at UC Riverside using genomics to examine changes in biodiversity. Their research spans a wide range of species – including the hops that make a Father’s Day beer possible – and showcases the power of HiFi sequencing to illuminate regions of the genome long considered out of reach. Their post shows us just how much there is to learn from the Y chromosome when we finally have the clarity to see it.
The X, Y, Zs, and Ws, of sex chromosomes
Sex chromosomes are fascinating, yet relatively understudied, regions of the genome. These chromosomes have long been of interest because of their role in sex-determination and fertility, but have been notoriously hard to sequence and assemble. Unlocking these regions in an assembly provides the opportunity to study the fundamental evolutionary forces that act on genomes.
Sex chromosomes evolve from autosomes, other ordinary chromosomes that are not involved in determining sex. In a heterogametic XY system like in humans, one sex has two alike (also known as homologous) chromosomes (XX females), while the other has two distinct chromosomes (XY males). In this system, the autosomes and the X chromosome are inherited in both females and males, while the Y chromosome is only inherited through males. This isn’t the case for every species, though. For certain organisms like some birds, fish, or plants with a ZW chromosome system, females are the sex to contain the two distinct sex chromosomes.
Figure 1. Key regions of sex chromosomes. XY chromosomes contain one or two pseudoautosomal regions (PARs), which share 100% sequence homology and freely recombine during meiosis. The Y chromosome contains a region of suppressed recombination (pink), sometimes called a sex-determination region (SDR) or male-specific region of the Y. In humans, the SDR has lost most genes and has accumulated many repeats.
Sex chromosomes typically contain a region lacking in recombination, sometimes referred to as a sex determination region (SDR; Figure 1) or male-specific region of the Y (MSY). Within the SDR are often sex-determining genes – genes that initiate female and male-specific development. There are benefits to reduced recombination, for example, linking together genes that provide sex-specific benefits like sperm-related genes on the Y. In most of the sex chromosomes examined so far, there are also regions outside the SDR, called pseudoautosomal regions (PAR) that are expected to recombine freely with a matching region on the X chromosome, aiding in the proper pairing of the XYs at meiosis.
Why sex chromosomes are difficult to assemble: repeats, repeats, repeats
While there are benefits to sex-linkage, there are also consequences to the lack of recombination in an SDR. These regions tend to undergo a process called “degeneration”, where repetitive sequences proliferate and over time genes can be lost. A classic example are the human XYs, where the Y chromosome has become much smaller than its X counterpart and very few genes remain (Figure 1). The suppressed recombination also drives divergence of XY copies, to the point where Y-linked reads do not map to the X. Moreover, the Y can also contain an increased number of structural variants (large and small) compared to the X. Thus, after their initial evolution, sex chromosomes continue to evolve in ways that make their assembly in a genome complicated (i.e., highly-repetitive, structurally variable, and effectively half-coverage in data compared to the autosomes if they’re sufficiently diverged).
It is common knowledge among the genomics community that the first draft of the human genome took approximately 13 years to complete and cost nearly 3 million dollars. It would take scientists almost 20 more years to fill in the remaining gaps and release the first human ‘Telomere to Telomere’ (T2T) assembly. The last of these gaps to fill in (and warranting a separate publication from the remainder of the genome) was the human Y chromosome, one of the two sex chromosomes carried by most mammalian systems, where the large tandem and inverted repeat arrays made the complete assembly previously intractable. They say space is the final frontier, but the Y chromosome has been efficiently evading human exploration while still residing on planet earth.
Outside of humans, Y chromosome assemblies are still vastly underrepresented. Around 80-90% of chromosome-scale reference genomes for males on NCBI (accessed: June 8, 2025) lack a Y chromosome (Figure 2). However, recent advances in sequencing technology and assembly methods, like longer reads that can better span complex, repetitive regions, have begun to shed light on the diversity of Y chromosome evolution across a variety of species.
Figure 2. Breakdown of Y chromosome assemblies on NCBI
On PAR: increasing the contiguity and completeness of Y chromosomes
The mammalian XYs arose from an ancestral autosome pair approximately 140-160 million years ago. Though most mammals display the typical heterogametic XY system, some species of voles prove that there is no one way to achieve functional sex determination. For example, previous research has shown that the creeping vole (Microtus oregoni) lacks a Y chromosome entirely, but still achieves male sex determination from a second X chromosome. Needless to say, we are a long way from understanding the diversity of Y chromosomes among species (as well as sex determination mechanisms), and recent human Y-profiling suggests we have even further to go in understanding what drives sex variability within species.
Nonetheless, recent assemblies in mammals have increased our understanding of Y chromosomes, such as in apes, providing us with knowledge of species- or clade-specific patterns and unlocking our ability to ask more advanced evolutionary questions. One observation is that primates (including humans) have two PARs, but most other mammals appear to only have a single PAR. One of these single PAR species is the lion, where recent assemblies increased the overall length of the assembled Y by 2.5 times, from 8.6 to 22 Mb (Figure 3). Sex chromosomes are not only important for investigating genome evolution and sex determination, but they can also tell us something about the dispersal patterns and population history of the different sexes.
Figure 3. Improved Y chromosome assembly for lions. In lions, Panthera leo, two genome assemblies were completed for an XY male. Both the 2023 and 2024 releases contain the pseudoautosomal region, but the 2024 release increased the assembled sequence of the SDR. The SDR was identified using male-specific k-mers, which are plotted in pink as a heatmap in the ideogram.
Making the Y a ‘mane’ event
Like other regions of the genome, understanding standing genetic variation on the Y for species of conservation concern is critical. The Y chromosome is expected to have lower levels of genetic variation at equilibrium compared to the autosomes, simply due to their numbers – at a population level there is one Y chromosome for every four autosomes. As such, the Y is expected to have a quarter of the genetic variation of autosomes. However, additional processes related to the lack of recombination can drive the level of genetic variation down further. This can be problematic for species with low effective population sizes, and compound the effects of low variation in Y-linked genes. Sex chromosomes can also help with understanding patterns of migration. Mitochondria (as well as chloroplasts in plants) are maternally inherited, permitting an understanding of female migration. Because the Y chromosome is the only genomic compartment that is inherited exclusively through males, the Y chromosome in a genome reference can aid in tracking male population history and effective size.
Lions are a species of conservation concern and have iconic sexual dimorphism between males and females in the form of the male lion’s mane. They have unique population dynamics, typically forming prides with 1-2 related males and multiple females. Oftentimes, only one of these males breeds and pride takeovers can result in the complete displacement of male lineages. Males generally disperse from their natal territory to strike out on their own. Interestingly, there are also a few reports of lion populations where females have developed manes and some severely bottlenecked populations have reports of reduced sperm motility. All of these biological observations are likely in part due to variation, or could be better understood by patterns of variation on the Y chromosome. And they are not the only feline where the sex chromosomes take a starring role: just recently, scientists elucidated the part X and Y chromosomes play in determining whether a cat is calico or ginger-colored.
Fully phased XY ‘hop-lotypes’ in hops
Plants are an exciting kingdom for examining sex chromosomes, because while only 5-10% of flowering plants have separate sexes, this trait has evolved hundreds to thousands of independent times. Thus, in plants we can gain new insight on some of the earliest stages of sex chromosome evolution. Curiously, many crops are dioecious (female and male reproductive organs in different individuals), like asparagus, pistachios, papaya, and beer hops, and understanding their sex chromosomes can be beneficial to breeding programs, because in many cases, only one sex develops the commercially important product, like fruits or seeds.
Figure 4. Phased XY assemblies for hops. In hops, Humulus lupulus, genomes were assembled for XY males of three botanical varieties used in breeding programs, Humulus lupulus vars. lupulus, lupuloides, and neomexicanus. The XY assemblies all match cytological expectations, with the H. lupulus var. lupulus Y being much smaller than its X counterpart, but vars. lupuloides, and neomexicanus are nearly the same size as the X (only the H. lupulus var. lupulus X is shown, as the other Xs show the same pattern). The SDRs were identified using male-specific k-mers, which are plotted in pink as a heatmap in the ideogram.
One of the first sex chromosome pairs identified in flowering plants was in the beer hop a century ago. Like the mammalian XY system, beer hops have ancient, heteromorphic XYs, where the Y chromosome is smaller than its X counterpart. The part of hops that are used in brewing beer are called “hop cones”, which are technically the female inflorescences, and imbibe beer with its characteristic bitterness and aroma. Despite the early identification of the XYs in hops, very little is known about the genes involved with determining whether a plant produces hops cones or pollen (i.e., female or male, respectively), in part due to a lack of XY references. However, recent assemblies were generated for three botanical varieties of hops that are used in breeding programs, the European hop, Humulus lupulus var. lupulus, and two American hop varieties, H. lupulus vars. lupuloides and neomexicanus (Figure 4). Although the hop Ys are highly-repetitive (95% repeats), they were assembled in very few pieces – in the variety Humulus lupulus var. lupuloides, the ~240Mb Y was assembled with a single contig. These references will help to uncover the genes associated with sex determination in hops and other sex-specific development in these economically important plants.
Putting the ‘W’ in ZWs
Outside of crops, some additional and evolutionarily important plants have evolved dioecy. Amborella trichopoda is the extant species that is in the sister lineage to the rest of flowering plants, having diverged ~140 MYA. Thus, Amborella holds an important phylogenetic position for comparative analyses across angiosperms. The ZW sex chromosomes in Amborella evolved more recently than the mammalian or hop systems, only ~5 MYA. Recent analyses successfully phased the ZW chromosomes, in addition to the autosomes, which were previously represented as a single, chimeric assembly (Figure 5). While the composition of the Z and W chromosomes are rather similar to one another, with very little gene loss and a surprisingly low repeat content, this was an important test for phasing less diverged sex chromosome pairs, and helped to provide an improved reference, for both haplotypes, of Amborella.
Figure 5. Improved W chromosome assembly for Amborella. For Amborella, the extant sister species to the rest of flowering plants, two genome assemblies were released for a ZW female. The 2022 release was a haploid representation of both parental haplotypes, and the sex chromosomes were a chimeric mix of Z-linked and W-linked regions. The 2024 release fully phased the W from the Z. The SDR was identified using female-specific k-mers, which are plotted in pink as a heatmap in the ideogram.
W, X, Y, or Z, we hope you’ll join us in celebrating the father figures in your life today. Whether they passed on a love of dad jokes, or simply a knack for grilling things to perfection, today’s the day to honor their contributions — genetic or otherwise. So raise a glass, fire up the grill, and thank the dads who helped make you who you are.