New end-to-end X and Y chromosome sequences reveal enormous diversity within the Y chromosome, providing insight into human evolution and disease as well as the conservation of endangered monkey genetics.
A collaborative research team created complete reference genomes for the sex chromosomes of many great and lesser apes, revealing rapid evolutionary changes, particularly in the Y chromosome. These findings advance our understanding of primate evolution and related human diseases by paving the way for future studies of monkey reproduction, fertility, and sex-specific genetic traits.
Examination of sex chromosomes of monkeys
An international team from Penn State, the National Human Genome Research Institute, and the University of Washington has created complete “end-to-end” reference genomes for the sex chromosomes of five great ape species and one great ape species. Their research revealed rapid evolutionary changes in the male-specific Y chromosome. This information improves our understanding of the evolution of sex chromosomes and contributes to the knowledge of genetic diseases that affect both monkeys and humans.
Importance of Y and X chromosomes in great apes
“The Y chromosome is important for human fertility, while the X chromosome contains genes important for reproduction, cognition and immunity,” said Kateryna Makova, the Verne M. Villaman Chair in Life Sciences and professor of biology at the University of Pennsylvania. leader of the study. set. “Our study opens the door to many future studies on sex chromosomes, how they evolve, and their associated diseases. All of the species of great apes we studied are in danger of extinction. The availability of complete sex chromosome sequences, their sex-specific distribution in the wild, and the genes important for reproduction and fertility.” “It will make the work on it easier.”
Recently constructed complete sex chromosome genomes of six primate species, created by an international collaboration led by Penn State researchers and the National Human Genome Research Institute, reveal the rapid evolution of the monkey Y chromosome. These findings could help protect these endangered species and shed light on sex-linked genetic diseases in both humans and our closest relatives. Credit: Design: Bob Harris; Photo credit: San Diego Zoo and Tulsa Zoo
Evolutionary understanding of Y chromosome variability
Such reference genomes serve as useful representative samples for future studies of these species. The team found that compared to the X chromosome, the Y chromosome differs greatly among monkey species and contains many species-specific sequences. But it is still subject to purifying natural selection, an evolutionary force that preserves its genetic information by eliminating harmful mutations.
The new study was recently published in the journal. Nature .
Technological progress in genomic sequencing
“In 2001, researchers sequenced the human genome, but it was not fully completed,” Makova said. “The technology available at the time meant that some gaps were not filled until renewed efforts by the Telomere-Telomere Consortium, or T2T, in 2022-23. Experimental and computational research developed by the Human T2T Consortium to determine the full sequence of the sex chromosomes of the great apes, our closest living relatives.” We used methods.”
Comparative genomics of great apes
The team produced complete sex chromosome sequences for the lesser siamang monkey, as well as five great ape species: chimpanzee, bonobo, gorilla, Bornean orangutan and Sumatran orangutan, which make up the majority of monkey species alive today. They sequenced one individual of each species. The resulting reference genomes serve as a map of genes and other chromosomal regions that can help researchers sequence and assemble the genomes of other individuals of the species. Previous sex chromosome sequences for these species were missing or unavailable for Bornean orangutans and siamangs.
“Sequencing the Y chromosome was challenging because it contains many repetitive regions, and because traditional short-read sequencing technology resolves sequences in short bursts, it is difficult to put the resulting segments in the correct order,” said postdoctoral researcher Karol Pahl. at Penn and was one of the first authors of the study. “T2T methods use long-read sequencing technologies that overcome this problem. This, combined with advances in computational analysis where we worked with Adam Phillippi’s group at NHGRI, allowed us to fully distinguish repetitive regions that had previously been difficult to sequence and assemble into X and Y.” “By comparing their chromosomes among themselves and across species, we learned a lot about their evolution, including the previously established human X and Y T2T sequences.”
High variability of the Y chromosome
“Sex chromosomes started out like any other chromosome pair, but the Y was unique in accumulating many deletions, other mutations, and repetitive elements because it did not exchange genetic information with other chromosomes for much of its length,” Makova said. Director of the Pennsylvania State Medical Genomics Center, Dr.
As a result, the research team found that across six species of monkeys, the Y chromosome is much more variable than the X for a variety of traits, including size. Among the great apes studied, the size of the In comparison, the Y chromosome ranges from 30 million DNA letters in the Siamese to 68 million letters in the Sumatran orangutan.
The amount of DNA sequence shared between species was also more variable in Y . For example, approximately 98% of the X chromosome is aligned between humans and chimpanzees, while only one-third of the Y is aligned between the two. The researchers found that this is partly because the Y chromosome is more likely to rearrange, or have parts of its genetic material duplicated.
Additionally, the percentage of the chromosome covered by repetitive sequences varies greatly by Y. Depending on the species, 62% to 66% of the X chromosomes are occupied by repetitive elements, while 71% to 85% of the Y chromosomes are occupied by repetitive elements. to them. These percentages are higher in both X and Y than in other chromosomes in the human genome.
Y chromosome survival strategies
“We found that monkey Y shrank, accumulated many mutations and duplications, and lost genes,” Makova said. “So why didn’t the Y chromosome disappear as some previous hypotheses suggested? In collaboration with Sergiy Kosakovsky Pond of Temple University and others, we found that the Y chromosome still has a number of genes that have evolved under purifying selection, a type of natural selection that keeps gene sequences intact “Many of these genes are important for spermatogenesis, which means the Y chromosome is unlikely to disappear any time soon.”
Researchers found that many genes on the Y chromosome use two strategies for survival. The first takes advantage of genetic redundancy (the presence of more than one copy of a single gene on a chromosome) so that intact copies of the gene can compensate for copies that may mutate. For the first time, the team quantified this genetic redundancy by completing the structure of multicopy gene families on the sex chromosomes of great apes.
A second survival strategy exploits palindromes, in which a sequence of letters in the DNA alphabet is followed by the same but inverted sequence, such as ACTG-GTCA. When genes are contained within a palindrome, they take advantage of the palindrome’s ability to correct mutations.
“We found that the Y chromosome can exchange genetic information with itself between the repetitive sequences of the two arms of the palindrome, which fold in such a way that the opposite sequences line up,” Pal said. “When two copies of the same gene are found in palindromes and one copy is affected by the mutation, the mutation can be rescued by genetic exchange with the other copy. This can compensate for the lack of exchange of Y genetic information with other chromosomes.”
The research team also obtained the complete palindrome sequences on the sex chromosomes of a great ape for the first time; because it was previously difficult to sequence and examine. They found that palindromes are particularly abundant and long in the monkey Y chromosome, but are generally shared only by closely related species.
Advances in monkey genome research
In collaboration with Michael Schatz and his team at Johns Hopkins University, the researchers also examined the sex chromosomes of 129 individual gorillas and chimpanzees to better understand genetic variation within each species and find evidence of natural selection and other evolutionary forces acting on them.
“We obtained important new information by aligning sex chromosome sequence reads from previously studied gorillas and chimpanzees with our new reference sequences,” said Zachary Spich, an associate professor of biology at the University of Pennsylvania and author of the paper. “While increasing sample sizes in the future will be very useful in improving our ability to detect signatures of different evolutionary forces, this can be ethically and logistically challenging when working with endangered species, so it is critical that we ensure we get the maximum return on research.” the data we have.”
Researchers investigated several factors that could explain Y chromosome variation in gorillas and chimpanzees, and this analysis found additional evidence of purifying selection on the Y. This confirms the role that such natural selection plays on Y. previous analyzes of genes.
Implications for future research and conservation efforts
“The powerful combination of bioinformatics methods and evolutionary analysis we use allows us to better elucidate the evolutionary processes acting on the sex chromosomes of the great apes, our closest living relatives,” said Christian Huber, professor of biology at the University of Pennsylvania. and the author of the article, document. “In addition, the reference genomes we created will be useful for future studies of primate evolution and human diseases.”
Source: Port Altele
