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

Complete X and Y chromosome sequences from six different primates species were successfully mapped, revealing the rich diversity among these species and providing deeper insight into their evolutionary processes. This large-scale genomic mapping highlights unique and shared traits across these species and offers a clearer understanding of their evolutionary trajectories.

A team of scientists funded by National Institute of Health (NIH) produced 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, indicating rapid evolution, in addition to revealing previously unexplored regions of great ape genomes. Since 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 species of apes, chimpanzees, bonobos, gorillas, and Bornean and Sumatran orangutans, as well as one other primate species more distantly related to humans, the siamang 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. “Previously, only the chimpanzee genome sequence was relatively complete, but even that still had large gaps, especially in repetitive regions DNA.”

Advances in DNA Analysis

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

Scientists compared monkey chromosome sequences with human X and Y chromosomes to understand their evolutionary history. Like the human X and Y chromosomes, the Y monkeys have far fewer genes compared to the X chromosomes. The researchers also used a computational method called alignment, which identifies regions of the chromosome 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 the 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 great ape Y chromosome sequences matched the human Y chromosome.

Surprising variations in Y chromosomes

“The extent of the differences between the Y chromosomes of these species was very surprising,” said Kateryna Makova, Ph.D., a 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 are evolving 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. Differences in the number and types of DNA repeats account for some of the differences in chromosome lengths.

One type of repeat is called a palindrome, a sequence of DNA that contains inverted DNA repeats. DNA palindromes are similar to language 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 forward and the same. back. However, DNA palindromes can be over a hundred thousand letters long.

Unique gene variation and future research

Scientists have discovered that DNA palindromes on the X and Y chromosomes of primates 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. Scientists suspect that the many copies in these palindromes help protect the genes, especially on the Y chromosome. Since there is typically only one Y chromosome in each cell, if a gene on the Y chromosome is damaged, there is no other chromosome with a copy of the gene. which can be used as a template to repair damage.

“Having these genes in palindromes is like keeping a backup copy,” said Adam Phillippy, Ph.D., principal investigator at NHGRI and lead author of the study. “We know that many of these genes have important functions, so we expected to see the same genes in palindromes in different species, but that doesn’t seem to be the case.”

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

“There may be even more variations that we’re not seeing yet,” said Dr. Phillippy. “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 extensive differences in Y chromosome gene copy number between humans and other great apes,” added Dr. Makova.

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

These sequences provide important insights into ape genomes 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 centromere sequences of these species were completely unknown prior to this study and other recent research efforts by many of the same researchers.

“After these satellite sequences from great apes open up new territory for exploration,” said Dr. Makova, “and similar to our other findings on the Y chromosome, we 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. Scientists are currently working on describing the entire genomes of these great ape species, but the sequences of the X and Y chromosomes themselves offer 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 in each cell, which leads to an accumulation of changes in the DNA sequence. Another evolutionary force, said Dr. Makova, is a phenomenon known as the male mutational 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 particularly affects the Y chromosome.

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

“It’s important to realize that all these great ape species are endangered,” said Dr. Poppy. “Not only can we learn about human evolution from these sequences, but we can use 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 Great Ape Sex Chromosomes” by Kateryna D. Maková, Brandon D. Pickett, Robert S. Harris, Gabrielle A. Hartley, Monika Čechová, Karol Pal, Sergej 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, By Evan E. Eichler and Adam M. Phillippy, 29 May 2024, Nature.
DOI: 10.1038/s41586-024-07473-2