Lynch Lab uses evolutionary genomics and comparative cell biology to study Peto’s paradox

Lynch Lab.

“Understanding how some animals evolved to be relatively cancer-free despite having giant bodies and living a really long time is all about understanding how evolution works,” says Vincent Lynch, associate professor of biological sciences, College of Arts and Sciences. “If you can figure out how it is these animals evolved to be relatively cancer-free, we can learn something about evolution and maybe that can teach us something about how we can treat cancer in humans.” Read more.

Research News

UB team explores cancer defenses of big, long-lived animals

Zoom image: Vincent Lynch (center), associate professor of biological sciences, studies how large and long-lived animals have evolved protections against cancer. Team members in his lab include master’s student Meaghan Birkemeier (left) and postdoctoral researcher Jacob Bowman (right). Photo: Douglas Levere Vincent Lynch (center), University at Buffalo associate professor of biological sciences, studies how large and long-lived animals have evolved protections against cancer. Team members in his lab include master’s student Meaghan Birkemeier (left) and postdoctoral researcher Jacob Bowman (right). Photo: Douglas Levere

Vincent Lynch (center), associate professor of biological sciences, studies how large and long-lived animals have evolved protections against cancer. Team members in his lab include master’s student Meaghan Birkemeier (left) and postdoctoral researcher Jacob Bowman (right). Photo: Douglas Levere

By ALEXIS NICHOLSON

Undergraduate medicinal chemistry major

Published April 11, 2022

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“Basically, it is all about being curious. It’s about understanding how biology and evolution work. ”
Vincent Lynch, associate professor
Department of Biological Sciences

When UB evolutionary biologist Vincent Lynch was in graduate school studying life history evolution, a scientific enigma known as Peto’s paradox intrigued him.

Cancer arises from an accumulation of mutations in individual cells over their lifetime, so it is to be expected that animals that live a longer time and have more cells would have a higher chance to acquire cancer. But they do not. Peto’s paradox revolves around this idea.

Lynch decided that when he started his faculty job, leading his own research, he wanted to explore why larger, long-lived animals didn’t develop cancer more often.

Growing up, Lynch, a first-generation college student, only knew of two occupations involving a biology major: doctor and teacher. It wasn’t until he got to college that he learned about research-based careers.

He hopes his work can lead him to discover information that can aid in advancements for cancer treatment and prevention in humans.

“Understanding how some animals evolved to be relatively cancer-free despite having giant bodies and living a really long time is all about understanding how evolution works,” says Lynch, associate professor of biological sciences, College of Arts and Sciences. “If you can figure out how it is these animals evolved to be relatively cancer-free, we can learn something about evolution and maybe that can teach us something about how we can treat cancer in humans.”

Zoom image: Meaghan Birkemeier adds trypsin to a cell culture flask that contains elephant cells growing in a red growth medium. Trypsin, an enzyme, helps to detach the cells from the surface of the flask. After separation, the cells will be frozen and stored for later use. Maintaining an inventory of cells, including back-ups, is a vital part of the research program. Photo: Douglas Levere Meaghan Birkemeier adds trypsin to a cell culture flask that contains elephant cells growing in a red growth medium. Trypsin, an enzyme, helps to detach the cells from the surface of the flask. After separation, the cells will be frozen and stored for later use. Maintaining an inventory of cells, including back-ups, is a vital part of the research program. Photo: Douglas Levere

Meaghan Birkemeier adds trypsin to a cell culture flask that contains elephant cells growing in a red growth medium. Trypsin, an enzyme, helps to detach the cells from the surface of the flask. After separation, the cells will be frozen and stored for later use. Maintaining an inventory of cells, including back-ups, is a vital part of the research program. Photo: Douglas Levere

Genomics, cell biology and ‘frozen zoos’

In the lab, Lynch’s team uses evolutionary genomics and comparative cell biology to study Peto’s paradox. Evolutionary genomics focuses on how an organism’s DNA has evolved over time. Comparative cell biology focuses on the similarities and differences between varied species’ cells.

To obtain cells and DNA for different critters, Lynch collaborates with “frozen zoos,” one of his favorites being the San Diego Zoo’s. These organizations collect and freeze cells of many species, including rarer or potentially at-risk species. By keeping and preserving cells, there is a record of these animals’ genetic information. 

As part of their work, Lynch and colleagues “stress out” animal cells in the lab as much as possible, and record and analyze the cells’ reactions to the stresses. Some cells persevere and adapt to the stresses, while other cells die. Once a cell is dead, scientists conduct further analysis on how it died and how long it took to die.

The results show that some animals, including elephants and Galápagos giant tortoises, are very sensitive to these stresses. This sensitivity makes their cells more susceptible to death, which can actually be beneficial. As Lynch explains, certain types of cell damage can increase cancer risk, so if potentially cancerous cells die quickly, tumors will be less likely to develop.

Another finding is the existence of multiple copies of tumor suppressor genes in these species.

In addition to elephants and tortoises, other creatures of interest in the Lynch lab’s cancer research include whales, bats, sloths, armadillos and aardvarks.

Zoom image: Jacob Bowman holds a cell culture flask that contains elephant cells growing in a red growth medium. Bowman’s research focuses in part on comparing the genes of modern elephants with their ancestors’ genes to learn about elephants’ potential defenses against cancer. Photo: Douglas Levere Jacob Bowman holds a cell culture flask that contains elephant cells growing in a red growth medium. Bowman’s research focuses in part on comparing the genes of modern elephants with their ancestors’ genes to learn about elephants’ potential defenses against cancer. Photo: Douglas Levere

Jacob Bowman holds a cell culture flask that contains elephant cells growing in a red growth medium. Bowman’s research focuses in part on comparing the genes of modern elephants with their ancestors’ genes to learn about elephants’ potential defenses against cancer. Photo: Douglas Levere

Collaborative, curiosity-driven lab

Work in the lab is a collaborative experience between Lynch, postdoctoral scientists and graduate students.

The lab is heavily driven by curiosity, and documentation is very important: If you have an idea or revelation, write it down. Writing everything down also helps keep track of any progress or setbacks.

“Basically, it is all about being curious,” Lynch says. “It’s about understanding how biology and evolution work. For the most part, once grad students and postdocs become familiar with what we do, they can do their own curiosity-driven experiments. It is pretty collaborative. We all learn from each other.”

Outside the lab, in a workspace shared by scientists from across the department, are huge dry erase boards filled with biological terms in an array of different colors: phenotype, recombination, selection, DNA, segments, duplication, interference. These words are all connected to each other with arrows and graphs, resembling a vision board.

Inside the lab, cells are kept in freezers until they are ready for use. One recent morning, the scientists are growing and experimenting with African elephant cells.

Growth media, which helps keep the cells alive when they aren’t frozen, and trypsin, an enzyme that breaks down proteins, are kept warm at 37.1 degrees Celsius.

In future research, the team will insert genes of elephant ancestors into the modern elephant cells. One of the questions the researchers are trying to answer is if the rate of apoptosis, also known as cell death, can be changed through the insertion of ancestor genes that suppress tumors.

Some important work related to the research is also done outside of the lab. Jacob Bowman, a postdoctoral scientist who has been a member of Lynch’s group for a year and a half, focuses in part on computational work, analyzing large amounts of genetic-sequencing data, which allows him to see how genes are evolving.

Bowman became interested in Lynch’s work after Lynch paid a visit to Ohio State University, which Bowman attended at the time. After hearing a lecture by Lynch, Bowman applied for a position with the lab. Bowman and Meaghan Birkemeier, a master’s student who recently joined Lynch’s research team, both share the sentiment that the lab environment is very nice and fluid.

I’m excited to have such a fascinating research project for my master’s degree. Dr. Lynch is approachable with any questions I have about my project and provides direction for my experiments as I work toward answering my research question,” says Birkemeier. “My fellow students make the lab a fun environment, and we learn from one another as we collaborate in our research.”

The lab environment is like a playground where we get to try a whole bunch of techniques and just explore new ideas all the time,” says Bowman. “We’re not expected to tackle a problem with one method, but with a myriad of tools that give us new information. Vinny’s excitement for the work and the process is infectious. It creates a positive and communicative lab atmosphere that is ideal for science.”

Faculty Profile

  • Vincent J. Lynch

    PhD

    Vincent J. Lynch, PhD.

    Vincent J. Lynch

    PhD

    Vincent J. Lynch

    PhD

    Research Interests

    Genetics, Genomics and Systems Biology; Evolutionary Biology.

    Education

    PhD, Ecology and Evolutionary Biology, Yale University, 2008

    MS, Ecology and Evolutionary Biology, Yale University, 2005

    BS, Biology and Anthropology, University at Albany, SUNY, 2002

    Office Hours

    Research Summary

    A major challenge in biology is to determine the genetic and molecular mechanisms responsible for phenotypic differences between species (DevoEvo), particularly mechanisms that underlie the origin of new anatomical structures (‘evolutionary novelties’), biological functions (‘evolutionary innovations’), and that limit biological possibilities (‘developmental constraints’). To explore how evolutionary novelties, innovations, and developmental constraints evolve we combine comparative genomics and experimental methods to deduce the molecular mechanisms that underlie the evolution of pregnancy and animals with extremely long lifespans and large body sizes, and the role evolutionary history plays in our susceptibility to diseases such as preterm birth and cancer. 

    Current Project

    Evolutionary mechanics of adhesion complexes that mediate Amniote hearing

    Selected Publications

    • VJ Lynch Relaxed constraint and functional divergence of the progesterone receptor (PGR) in the human stem-lineage M Marinić, , PLoS Genetics 16 (4), e1008666
    • E Fry, SK Kim, S Chigurapti, KM Mika, A Ratan, A Dammermann, Brian J. Mitchell, Webb Miller, Vincent J Lynch (2020) Functional architecture of deleterious genetic variants in the genome of a Wrangel Island mammoth. Genome Biology and Evolution 12 (3), 48-58
    • JM Vazquez, VJ Lynch. Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk. bioRxiv
    • M Marinic, K Mika, S Chigurupati, VJ Lynch, Evolutionary transcriptomics implicates HAND2 in the origins of implantation and regulation of gestation length. bioRxiv
    • Erin Fry, Sun K. Kim, Sravanthi Chigurapti, Katelyn M. Mika, Aakrosh Ratan, Alexander Dammermann, Brian J. Mitchell, Webb Miller, Vincent J. Lynch (2020) Functional architecture of deleterious genetic variants in the genome of a Wrangel Island mammoth. Genome Biology and Evolution, evz279.
    • Vazquez JM, Sulak M, Chigurupati S, Lynch VJ (2018) A Zombie LIF Gene in Elephants Is Upregulated by TP53 to Induce Apoptosis in Response to DNA Damage. Cell Rep. 24(7):1765-1776.
    • Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ (2016) TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. Elife. 5: e11994.
    • Lynch VJ, Nnamani MC, Kapusta A, Brayer K, Plaza SL, Mazur EC, Emera D, Sheikh SZ, Grützner F, Bauersachs S, Graf A, Young SL, Lieb JD, DeMayo FJ, Feschotte C, Wagner GP (2015) Ancient transposable elements transformed the uterine regulatory landscape and transcriptome during the evolution of mammalian pregnancy. Cell Rep. 10(4):551-61.