In nature the non-human primates are our closest relatives. By studying them we can know more about our origins and development. Specifically, the evolution of the Y chromosome is a key area of interest due to its implications for human health.
Although the sex chromosomes of human and some great apes have already been analyzed, much is still unknown for most primates. In the latest research published in Nature Ecology & Evolution, a team of international scientists from Zhejiang University, Aarhus University, Kunming Institute of Zoology, Northwest University, and BGI-Research used whole-genome sequencing data to reconstruct the evolutionary trajectory of the primate sex chromosomes.
Eighty million years of rapid evolution of the primate Y chromosome published in Nature Ecology & Evolution.
In this new study, 19 primate sex chromosome assemblies were newly generated and analyzed along with 10 existing assemblies. The research team reported a rapid evolution of the Y chromosome across primates. By exploring and comparing genomic sequence of the sex chromosomes across different species, this research shed the light on the diversity of mating systems across species as well as sex chromosome evolutionary outcomes over the last 80 million years.
Distinguishing X and Y
The genetic basis for sex determination in primate are the sex chromosomes. In male there are the X and Y chromosomes and in female there are two X chromosomes. The sex chromosomes also play an important role in many evolutionary processes, including genomic conflict, adaptation and speciation. Interestingly, significant differences are found in length and genetic content between the X and Y chromosomes. In humans, the X chromosome is around 156 Mb in length and contains over 850 protein-coding genes, while the Y chromosome has experienced extreme degeneration, resulting in just 57 Mb in length and only 48 protein-coding genes.
It is now commonly accepted that the human X and Y chromosome originated from a pair of ancestral autosome at the most recent common ancestor (MRCA) of the therian, a subclass of mammals, about 180 million years ago. The human Y chromosomes have deteriorated to be only around 1/3rd the length of the X chromosomes. Other examples of this degeneration include gorilla and mouse, whose Y chromosomes are around 20% and 50% the length of the X chromosomes, respectfully.
But why would the Y chromosome degenerate? Looking back at its evolution, sex-determining gene appeared on the Y chromosome and natural selection led to recombination suppression with the X chromosome. This recombination suppression also led to Y chromosomes struggling to avoid potentially harmful mutations, which were the cause of its degeneration over time.
Different species, different chromosomes
The research successfully constructed high-quality X and Y chromosome sequences for 19 species using long-read sequencing technology, broadening the range of availability of the sex chromosome assembly in primates. By the in-depth analysis the research team found that even primates – humans’ closest relatives – have evolved into significant differences in their Y chromosomes over time. For example, the pygmy slow loris (Nycticebus pygmaeus) of family Lorisdae has the longest Y chromosome among all primates (109.66 Mb, or about 60% of its X chromosome), while the Y chromosome of Hamadryas baboon (Papio hamadryas) has been found to be even shorter than that of human (only 16.24 Mb, or 10% of their X chromosome).
Another important finding was that, except for the heterochromatin region which comprises short repeat sequences, the differences in Y chromosome length across species were mainly contributed by the varying sizes of the ampliconic region. These regions contains large and highly identical sequences and usually form palindrome structure. The study also found that different ampliconic regions were expanded across different species. For example, DDX3Y , the Y gene is responsible for sperm development, was only found to be amplified in Platyrrhini. This might be associated with the intense sperm competition due to the polygamous mating system of these primates.
Autism as an evolutionary byproduct
Because the primate Y chromosome was inhibited from recombining with the X chromosome during evolution, it rapidly accumulated a large number of mutations which resulted in functional degeneration and loss of most ancestral genes. To date only around 10% of the Y chromosome genes were retained over time, and different genes were found retained in different species.
One of the most notable Y genes in primates is NLGN4Y, since it have been commonly preserved in half of the 29 primates, including humans. The gene was considered responsible for synaptic formation in the nervous system. Comparing to its X homolog, NLGN4X, one single amino acid might be the pathogenic mechanism for male bias in NLGN4X-associated autism spectrum disorder. Utilizing the sex chromosome sequences from multiple primates, the researchers determined that this critical difference may have occurred at the MRCA of Simiiformes. This suggests that this mutation may have important implicant in the male development for Simiiformes. Such mutation may accidently cause a side effect of autism bias in male
Stratums in sex chromosome evolution
Over the past 180 million years, the sex chromosomes of humans have undergone several episodes of recombination suppression, leading to massive structural and sequence divergence between X and Y chromosomes. It is well established that recombination suppression between the sex chromosomes gradually evolves over time, leading to a reduction in pseudoautosomal region (PAR) size and the emergence of new evolutionary strata corresponding to cessation of recombination at different evolutionary timepoints.
By the comprehensive comparison across the primate sex chromosome, the research found a total of six evolutionary strata (S1-S6) in the primate lineage. Among them, the oldest three were formed long before the primates divergence. And after primate diversification, three additional strata were established, along with at least six PAR reduction.
For example, the sex chromosomes of prosimian species (such as the pygmy slow loris) are more primitive; they have longer PARs, retain the sex chromosomes of the primate ancestors, and have only three strata (S1-S3). As evolution continued, a new evolutionary stratum, S4, was emerged in the MRCA of Simiiformes. Platyrrhini (such as the golden snub-nosed monkeys) and Catarrhini (including the black-handed spider monkeys of the Americas) experienced further Y chromosome degeneration after their divergence, resulting in a new stratum, S5, independently evolved in the two lineages. The youngest stratum, S6, is currently only found in common marmosets.
Ethical approval was obtained for this research.
Source: Zhou Y, Zhan X-Y, et al. 2023. Eighty million years of rapid evolution of the primate Y chromosomes. Nature Ecology & Evolution. https://doi.org/10.1038/s41559-022-01974-x