Surprising evolutionary insights revealed by first complete great ape chromosome sequences

Complete the X and Y chromosome sequences of six different primates species have been successfully mapped, revealing the rich diversity among these species and providing deeper insight into their evolutionary processes. This extensive genomic mapping highlights the unique and shared characteristics of these species, offering a clearer understanding of their evolutionary trajectories.

A team of scientists funded by National Institutes of Health (NIH) generated the first complete chromosome sequences from nonhuman primates. Published today (May 29) in the magazine Nature, these sequences reveal remarkable variation between the Y chromosomes of different species, demonstrating rapid evolution, while revealing previously unexplored regions of the great ape genome. Because these primate species are humans’ closest living relatives, the new sequences may 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 great ape species, chimpanzees, bonobos, gorillas, orangutans from Borneo and Sumatra, as well as another primate species closely related to humans, the siamang gibbon.

“These chromosomal sequences add a significant amount of new information,” said Brandon Pickett, Ph.D., a postdoctoral fellow at the National Human Genome Research Institute (NHGRI), part of the NIH, and an author of the study. “Only the chimpanzee genome sequence was fairly complete before this, but even that still had large gaps, particularly in repeat regions DNA.”

Advances in DNA analysis

By analyzing these new sequences, the researchers estimated that 62 to 66% of the X chromosome and 75 to 82% of the Y chromosome are composed of repetitive DNA sequences. It is much more difficult for scientists to characterize these sequences, and the study of repetitive DNA has only become possible in recent years thanks to new DNA sequencing technologies and analysis methods.

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

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

Surprising variations of the Y chromosome

“The range of 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 diverged from the human lineage only seven million years ago, which is not a long time in evolutionary terms. This shows that Y chromosomes evolve very quickly.”

A significant 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. Variations 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 linguistic palindromes such as “race car” or “kayak”, in which the letters in the first half of the word are repeated in reverse in the second half of the word, so that the order of the letters is the same forwards and backwards. However, DNA palindromes can have more than a hundred thousand letters.

Unique gene variations and future research

The researchers found that DNA palindromes on primate X and Y chromosomes almost always contain genes that are repeated in many copies along the length of the chromosome. Most genes in primate genomes have only two copies, one on each chromosome of a pair. Researchers suspect that having a large number of copies in these palindromes helps protect the genes, especially on the Y chromosome. Since there is usually 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,” said Adam Phillippy, Ph.D., senior research scientist at NHGRI and senior author of the study. “We know that many of these genes perform important functions, so we expected to see the same genes in palindromes in different species, but that doesn’t seem to be the case.”

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

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

“However, we have some insights from our group’s previous work that suggest large variations in Y chromosome gene copy number in humans and other apes,” added Dr. Makova.

These great ape chromosome sequences also distinguish sequences of another type of repeat called satellite DNA, which is a large string of repetitive sequences. Among the chromosomes of great apes, researchers have 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 region called the centromere, and help chromosomes organize themselves during cell division. The centromere arrays of these species were completely unknown prior to this study and another recent research effort by many of the same researchers.

“Having these satellite sequences from great apes opens up new territory for research,” 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. Researchers are currently working to describe the entire genomes of these great apes, but even on their own, the X and Y chromosome arrays offer many insights, particularly about the evolutionary forces on the Y chromosome that contribute to its rapid evolution.

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

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

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

Reference: “Complete Sequence and Comparative Analysis of Monkey Sex Chromosomes” 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 JC Craig, Luciana de Gennaro, Mark Diekhans, Amalia Dutra, Gage H. Garcia, Patrick GS 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, Xinru Zhang, Zachary A. Szpiech, Christian D. Huber, Jennifer L. Gerton, Soojin V. Yi, Michael C. Schatz, Ivan A. Alexandrov, Sergey Koren, Rachel J. O’Neill, Evan E. Eichler and Adam M. Phillippy, 29 May 2024, Nature.
DOI: 10.1038/s41586-024-07473-2