New research that has successfully sequenced and assembled the traditionally difficult Y chromosome is providing a clearer picture into human fertility, as well as the ability to track male lineages in great apes, which can help with conservation efforts.
In a recent paper, an interdisciplinary team of biologists and computer scientists at Penn State sequenced and assembled the Y chromosome from orangutan and bonobo and compared those sequences to the existing human, chimpanzee and gorilla Y sequences.
Monika Cechova, graduate student and co-first author of the paper, said the Y chromosome is often left out of genomic studies since it is so difficult to assemble and sequence. It’s also unusual in that it doesn’t have a partner and contains relatively few genes contains, large sections of repetitive DNA and large DNA palindromes. That being said, the Y chromosome is critical for sex determination and male fertility. In humans, it harbors azoospermia factor regions, deletions of which can cause infertility. In mammals, the Y is needed to obtain a complete picture of mammalian genome evolution.
"There aren't out-of-the-box software packages to deal with the Y chromosome, so we had to overcome these hurdles and optimize our experimental and computational protocols, which allowed us to address interesting biological questions,” Cechova explained.
One of the questions was raised by previous work from the team that unexpectedly suggested that while humans are more closely related to chimpanzees overall, the human Y was more similar to the gorilla Y for some characteristics.
To glean more information, the researchers examined the Y chromosome of more great ape species, including a bonobo, a close relative of the chimpanzee, and an orangutan, a more distantly related great ape. Results from the new sequences revealed that the bonobo and chimpanzee shared the unusual pattern of accelerated rates of DNA sequence change and gene loss, suggesting that this pattern emerged prior to the evolutionary split between the two species.
The researchers believe this could be related to “sperm competition.” Female chimpanzees and bonobos mate with multiple males during a single cycle, forcing sperm from several individuals to race to fertilize a single egg.
“We think that this situation could provide the evolutionary pressure to accelerate change on the chimpanzee and bonobo Y chromosome, compared to other apes with different mating patterns, but this hypothesis, while consistent with our findings, needs to be evaluated in subsequent studies,” explained Rahulsimham Vegesna, also a graduate student and co-first author of the paper.
The results also allowed the researchers to map out what the Y chromosome might have looked like in the ancestor of modern great apes. For example, the Y’s many repetitive regions and palindromes—which makes the chromosome unusual by modern times—were actually already present on the ancestral chromosome.
“This argues for the importance of these features for the Y chromosome in all great apes and allows us to explore how they evolved in each of the separate species,” said Vegesna.
Since sperm competition does not occur in humans, gaining insight into how the Y chromosome evolved and diverged in humans and mammals—and how it operates today—could help solve some male infertility problems. For bonobos and orangutans, the resultant Y assemblies can be used to develop genetic markers to track male dispersal. This is critical for conservation genetics efforts as both species are endangered due to habitat loss.
Photo: Researchers have reconstructed the ancestral sequence of the great ape Y chromosome by comparing three existing (gorilla, human, and chimpanzee) and two newly generated (orangutan and bonobo) Y chromosome assemblies. Credit: Dani Zemba and Monika Cechova, Penn State