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  • Evolutionary biologist to study chromosome evolution and the consequences of sex chromosome fusions

Evolutionary biologist awarded nearly $2 million to study chromosome evolution and the consequences of sex chromosome fusions

Monday, August 14, 2023

Ryan Bracewell.
Ryan Bracewell. Courtesy photo

Widespread variation exists between species in the size, shape, and number of chromosomes, and these differences can have profound influences on genetic variation and reproductive compatibility. Ryan Bracewell, an assistant professor in the College of Arts and Sciences’ Department of Biology at Indiana University Bloomington, and members of his research lab focus on sex chromosomes in their quest to gain a better understanding of the genomic outcomes of transitions in chromosome number and structure.

One of the most pronounced genomic changes that can occur is when a chromosome—the fundamental structure necessary for the transmission of genetic information—becomes involved in sex determination. Over time, sex chromosomes typically diverge quite noticeably in gene content, gene expression, transposable element content, and levels of genetic diversity. These types of chromosomal changes can be the root of a surprising amount of variation.

Research suggests sex chromosomes play a major role in the evolution of reproductive incompatibilities and, thus, the formation of new species. Over evolutionary time, some old sex chromosomes can fuse to autosomes, creating so-called neo-sex chromosomes, that quickly differentiate and evolve dramatic differences in gene expression and gene content.

Diagram of a heteromorphic sex chromosome fusing to an autosome causing a neo-sex chromosome.
Sometimes ‘old’ heteromorphic sex chromosomes fuse to autosomes causing neo-sex chromosomes. Image courtesy of Ryan Bracewell

National Institutes of Health has awarded nearly $2 million to Bracewell through a Maximizing Investigators' Research Award for Early Stage Investigators (R35) to investigate chromosome evolution and consequences of rapid Y chromosome degeneration. The MIRA, as the award is known, is presented by the National Institute of General Medical Sciences, a section of the NIH. It provides support for an investigator's research that falls within the mission of NIGMS. The MIRA provides researchers with greater stability and flexibility which in turn enhances scientific productivity and the chances for important breakthroughs. The award is for five years.

The Bracewell lab will use genomics and bioinformatics-based approaches to examine chromosome evolution and changes in genome structure in fruit flies (Drosophila), one of the most powerful and heavily studied systems in genetics. The unique features of Drosophila—numerous species, small genomes, few chromosomes, ease of karyotyping—make a large-scale comparative analysis tracking the fates of chromosomes and their associated genes possible. The analyses will for the first time systematically identify genus-wide chromosome evolution and constraints on gene order and organization.

Comparisons of Drosophila genome structure: karyotyping, genome assembly and Hi-C scaffolding, and comparisons using phylogenetic context.
Comparisons of Drosophila genome structure: Bracewell’s research will use advances in genome sequencing and assembly to understand the evolution of genome structure across the genus Drosophila. Diagram courtesy of Ryan Bracewell

Bracewell will also be studying bark beetles as a model system in the project.

“We're initially looking at the mountain pine beetle and some of its close relatives within the genus since several have weird sex chromosomes,” Bracewell explained. “The bark beetle system is one-of-a-kind and gives us the unique opportunity to peek into a narrow window of time when multiple neo-Y chromosomes are present and degenerating.”

Ryan Bracewell, wearing goggles and a yellow helmet, uses a chainsaw to cut down a pine tree in a snow-covered forest.
Bark beetles in the genus Dendroctonus attack and kill conifers, requiring Bracewell and his team to be both geneticists and part-time lumberjacks. Photo courtesy of Ryan Bracewell
Two women look for beetles under the loose bark of a pine tree.
Lab members Camille Pushman and Medhavi Verma collect beetles from underneath the bark. Photo courtesy of Ryan Bracewell
Mountain pine beetle.
Dendroctonus bark beetles are small and many have neo-sex chromosomes. Photo by Ryan Bracewell

Another aspect of Bracewell’s research will be to investigate multiple Y chromosome types that are likely responsible for the evolution of reproductive incompatibilities between populations of beetle. The research will use several cutting-edge genomics techniques to help characterize these recently formed Y chromosomes and will then be coupled with population genomics to help characterize genetic exchange (or lack thereof) in natural populations.

Together, these projects will take advantage of the unique attributes of two insect systems to understand the processes that lead to major changes in karyotype as well as variation in degeneration and gene regulation of young sex chromosomes. More broadly, Bracewell's investigation will provide a deeper understanding of the maintenance of, and variation in, chromosome structure and function.

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