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Complete X and Y chromosome sequences from six different primates kinds have been successfully mapped, revealing a 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 revealed remarkable variation among the Y chromosomes of different species, indicating rapid evolution, in addition to revealing previously unstudied regions of 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 chromosomes from five species of monkeys, chimpanzees, bonobos, gorillas, and Bornean and Sumatran orangutans, as well as another primate species more distantly related to humans, the Siamese gibbon.

“These chromosome 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 relatively complete before this, but even that still had large gaps, particularly in regions of repetitive DNA.”

Complete X and Y chromosome sequences from six primate species reveal species diversity and insights into evolution. Credit: Ernesto Del Aguila III, National Human Genome Research Institute

Advances in DNA Analysis

By analyzing these new sequences, the researchers estimate that 62 to 66 percent of X chromosomes and 75 to 82 percent of Y chromosomes are made up of repetitive DNA sequences. These sequences are much more challenging for scientists to characterize, and the study of repetitive DNA has only become possible in recent years due 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 human X and Y, the Y chromosomes of the great ape have far fewer genes than the X chromosomes. The researchers also used a computational method called alignment, which shows regions of the chromosome that have remained relatively the same over the course of evolution, revealing the effects of different evolutionary pressures on different parts of the genome.

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

Surprising variations in Y chromosomes

“The degree of differences between the Y chromosomes of these species was very surprising,” said Dr. Katerina Makova, 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 terms of evolution. This shows that 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. Variations in the number and types of DNA repeats explain 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”, where the letters in the first half of the word are repeated backwards in the second half of the word, so that the sequence of letters is the same forward and backward. However, DNA palindromes can be over a hundred thousand letters long.

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 in a pair. The researchers suspect that having many copies in these palindromes helps protect the genes, especially on the Y chromosome. Because there is normally 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 Filippi, Ph.D., senior research scientist at NHGRI and senior author of the study. “We know that many of these genes have important functions, and so we expected to see the same genes in palindromes across species, but this does not appear to be the case.”

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

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

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

These great ape chromosome sequences also resolved 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 insight into the genomes of great apes because DNA satellites are present in the genome. Specifically, they are concentrated near the ends of chromosomes, called telomeres, and in another region called the centromere, which helps chromosomes organize themselves during cell division. The centromeric sequences 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 like our other findings on the Y chromosome, we can see that the centromere of the Y chromosome is highly 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 complete genomes of these great ape species, but even on their own, the X and Y chromosome sequences offer many insights, particularly about the evolutionary forces of the Y chromosome that contributed to its rapid evolution.

One factor is that there is usually only one Y chromosome per cell, leading to an accumulation of DNA sequence changes. 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 chance that the DNA sequence will change. This affects all chromosomes, but is particularly impactful on the Y chromosome.

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

“It’s important to remember that all of these monkey species 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: “The complete sequence and comparative analysis of ape sex chromosomes” by Katerina D. Makova, Brandon D. Pickett, Robert S. Harris, Gabrielle A. Hartley, Monica Chekhova, Carol Pal, Sergey Nurk, Dong An Yu, 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 S. McCoy, Paul Medvedev, Karen H. Miga, Catherine M. Munson, Eugenia Pak, Benedict Patten, Brendan J. Pinto, Tamara Potapova, Arang Ri, Joanna L. Rocha, Fedor Ryabov, Oliver A. Ryder, Samuel Sacco, Kishvar Shafin, Valery A. Shepelev, Vivian Slon, Steven J. Solar, Jessica M. Storer, Peter H. Sudmant, Swithalana, Alex Sweeton, Michael G. Tasia, Francoise Thibault-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. Filippi, 29 May 2024 ., Nature.
DOI: 10.1038/s41586-024-07473-2