Surprising evolutionary insights revealed by first complete chromosome sequences of great apes

Complete X and Y chromosome sequences from six different primates kind have been successfully mapped, revealing rich diversity among these species and providing deeper insights into their evolutionary processes. This comprehensive genomic mapping highlights the unique and shared features of these species, providing a clearer understanding of their evolutionary pathways.

A team of scientists funded by the National Institutes of Health (NIH) has generated the first complete chromosome sequences from non-human primates. Published today (May 29) in the magazine Naturethese sequences reveal remarkable variation among the Y chromosomes of different species, demonstrating rapid evolution, in addition to revealing previously unstudied regions of great ape genomes. Because these primate species are humans’ closest living relatives, the new sequences could provide insight into human evolution.

The researchers focused on the X and Y chromosomes, which play a role in sexual development and fertility, among many other biological functions. They sequenced the chromosomes of five species of great apes: chimpanzees, bonobos, gorillas, and Bornean and Sumatran orangutans, as well as another primate species more closely related to humans, the siamang gibbon.

“These chromosome sequences add a significant amount of new information,” said Brandon Pickett, Ph.D., a postdoctoral researcher at the National Human Genome Research Institute (NHGRI), part of NIH, and author of the study. “Only the chimpanzee genome sequence was reasonably complete before this, but even that still showed large gaps, especially in areas with repetitive DNA.”

Advances in DNA analysis

Analyzing these new sequences, the researchers estimated that 62 to 66% of X chromosomes and 75 to 82% of Y chromosomes consist of repetitive DNA sequences. Characterizing these sequences is much more challenging for scientists, and studying repetitive DNA has only become possible in recent years thanks to new DNA sequencing technologies and analysis methods.

The researchers compared the sequences of the monkey’s chromosomes with the human X and Y chromosomes to understand their evolutionary history. Like the human X and Y, the great ape Y chromosomes have far fewer genes compared to the X chromosomes. The researchers also used a computational method called alignment, which pinpoints regions of the chromosome that have remained relatively the same over evolution, revealing the effects of different evolutionary pressures on different parts of the genome.

The researchers found that more than 90% of the monkey’s X chromosome sequences matched the human X chromosome, showing that the X chromosomes have remained relatively unchanged over millions of years of evolution. However, only 14% to 27% of monkey Y chromosome sequences aligned with the human Y chromosome.

Surprising variations in Y chromosomes

“The magnitude of the differences between the Y chromosomes of these species was very surprising,” said Kateryna Makova, Ph.D., professor at Pennsylvania State University and leader of the study. “Some of these species only diverged from the human lineage seven million years ago, which isn’t a lot of time in terms of evolution. This shows that the Y chromosomes evolve very quickly.”

A notable difference between primate Y chromosomes is their length. For example, the Y chromosome of the Sumatran orangutan is twice as long as the Y chromosome of the gibbon. Variation in the number and types of DNA repeats are responsible for some of the differences in chromosome lengths.

One type of repeat is called a palindrome, a DNA sequence that contains inverted DNA repeats. DNA palindromes are similar to language palindromes such as ‘race car’ or ‘kayak’, where the letters in the first half of the word are repeated in reverse order in the second half of the word, so the order of the letters is the same forward and backward . However, the DNA palindromes can be more than a hundred thousand letters long.

Unique gene variations and future research

The researchers discovered that the DNA palindromes on the X and Y chromosomes of primates almost always contain genes, which repeat in many copies along the length of the chromosome. Most genes in primate genomes have only two copies, one on each chromosome in a pair. Researchers suspect that having many copies in these palindromes helps protect genes, especially on the Y chromosome. Because there is typically only one Y chromosome per cell, if a gene on the Y chromosome is damaged, there is no other chromosome with a copy of the gene that can be used as a template to repair the damage.

“Having these genes in palindromes is like keeping a backup copy,” said Adam Phillippy, Ph.D., senior investigator at NHGRI and senior author of the study. “We know that many of these genes perform important functions, and so we expected to see the same genes in palindromes across species, but this does not seem to be the case.”

The researchers studied different groups of genes in the palindromes, many of which play a role in sperm production and are therefore important for fertility. Although palindromes were found on all primate Y chromosomes studied, the specific palindrome sequences and the genes within these palindromes were often different for each species.

“There may be even more variation that we’re not seeing yet,” said Dr. Phillippy. “On the human Y chromosome, some genes can vary in number from individual to individual. For each of these other primate species, we only look at one individual. We don’t yet know what the rest of the population looks like and what other variations we might encounter.”

“However, we have some insights from previous work by our group that indicate extensive variation in the copy number of Y chromosome genes in humans and other monkeys,” added Dr. Makova added.

These great ape chromosome sequences also resolve the sequences of another type of repeat called a DNA satellite, which is a large stretch of repetitive sequence. Among the great ape chromosomes, the researchers identified several previously unknown, species-specific satellite sequences.

These sequences provide important insights into the genomes of great apes, as DNA satellites are present throughout the genome. Specifically, they are concentrated near the ends of chromosomes, called telomeres, and in another area called a centromere, which helps the chromosomes organize during cell division. The centromere sequences of these species were completely unknown before this study and another recent research effort conducted by many of the same researchers.

“Now these satellite sequences of great apes open up new territory to explore,” said Dr. Makova, “and similar to our other findings on the Y chromosome, we can see that the centromere of the Y chromosome is very dynamic.”

Implications for conservation and understanding evolution

These chromosome sequences can help researchers study the evolution of great apes, including humans. The researchers are currently working to describe the complete genomes of this great ape species, but even on their own, the X and Y chromosome sequences provide many insights, especially about the evolutionary forces on the Y chromosome that contribute to its rapid evolution.

One factor is that there is typically only one Y chromosome per cell, leading to the accumulation of changes in the DNA sequence. Another evolutionary force, said Dr. Makova, is a phenomenon known as male mutation bias. Compared to egg production, sperm production involves more DNA replication. With each replication there is a chance that the DNA sequence will change. This affects all chromosomes, but especially affects the Y chromosome.

Another potential factor is having a small population size, which can affect evolutionary rate. Not only do these monkey species have limited populations in the wild, but the Y chromosomes are only present in half the population, further limiting the effective population size of this particular part of the genome.

“It is important to remember that these great ape species are all endangered,” says Dr. Makova. “Not only can we learn about human evolution from these sequences, but we can also apply what we know about their genomes and human genomes to better understand the biology and reproduction of these endangered species.”

Reference: “The Complete Sequence and Comparative Analysis of Monkey Sex Chromosomes” by Kateryna D. Makova, Brandon D. Pickett, Robert S. Harris, Gabrielle A. Hartley, Monika Cechova, Karol Pal, Sergey Nurk, DongAhn Yoo, Qiuhui Li, Prajna Hebbar , Barbara C. McGrath, Francesca Antonacci, Margaux Aubel, Arjun Biddanda, Matthew Borchers, Erich Bornberg-Bauer, Gerard G. Bouffard, Shelise Y. Brooks, Lucia Carbone, Laura Carrel, Andrew Carroll, Pi-Chuan Chang, Chen -Shan Chin, Daniel E. Cook, Sarah J.C. Craig, Luciana de Gennaro, Mark Diekhans, Amalia Dutra, Gage H. Garcia, Patrick G.S. Grady, Richard E. Green, Diana Haddad, Pille Hallast, William T. Harvey, Glenn Hickey, David A. Hillis, Savannah J. Hoyt, Hyeonsoo Jeong, Kaivan Kamali, Sergei L. Kosakovsky Pond, Troy M. LaPolice, Charles Lee, Alexandra P. Lewis, Yong-Hwee E. Loh, Patrick Masterson, Kelly M. McGarvey, Rajiv C. McCoy, Paul Medvedev, Karen H. Miga, Katherine M. Munson, Evgenia Pak, Benedict Paten, Brendan J. Pinto, Tamara Potapova, Arang Rhie, Joana L. Rocha, Fedor Ryabov, Oliver A. Ryder, Samuel Sacco, Kishwar Shafin, Valery A. Shepelev, Viviane Slon, Steven J. Solar, Jessica M. Storer, Peter H. Sudmant, Sweetalana, Alex Sweeten, Michael G. Tassia, Françoise Thibaud-Nissen, Mario Ventura, Melissa A. Wilson, Alice C. Young, Huiqing Zeng, Evan E. Eichler and Adam M. Phillippy, May 29, 2024, Nature.
DOI: 10.1038/s41586-024-07473-2