About This Project

Polar bears survive almost entirely on seal fat. Yet unlike humans who eat high-fat diets, polar bears never develop diabetes, or heart disease. We hypothesize that their unique adaptations in adipose tissue enable extreme lipid metabolism without triggering inflammation or cardiometabolic disease. We will identify the gene regulatory switches that allow that generating the first-ever polar bear ATAC-seq data from fat to map where genes are turned on or off.

Ask the Scientists

What is the context of this research?

Polar bears split from brown bears less than 500,000 years ago — a blink of an eye in evolutionary time. In that short period, they transformed from omnivores eating mostly everything — well, you know bears are not generally picky — to hypercarnivores consuming almost pure fat. When humans eat diets this high in fat, they develop obesity, clogged arteries, diabetes, and heart disease. Yet polar bears show no signs of these conditions. Previous research has found that polar bears have mutations in genes like APOB, which controls blood cholesterol levels in mammals. But those studies only looked at changes in protein-coding genes, which are less than 2% of the genome. The real action in evolution happens in the other 98%, the regulatory regions that act like switches, controlling gene expression. We hypothesized that key adaptations to the high-fat diet lie in these regulatory regions, particularly those controlling lipid metabolism genes.

What is the significance of this project?

This will be the first-ever map of gene regulatory activity, which genes are turned on or off in each cell, in polar bear tissues. Polar bears have essentially solved the biological puzzle of processing enormous amounts of dietary fat without developing diabetes, or heart disease.

The regulatory regions we identify could point to new therapeutic targets for treating human metabolic and heart diseases. Health applications may not be immediate, but the methods we're developing will open doors for research in several fields: therapy development, better models for heart disease progression, understanding how species rapidly adapt to extreme environments.

No one has ever studied these regulatory regions in polar bears. We don't know which tissues experienced the most dramatic regulatory changes, or which genes are being controlled differently than in their brown bear relatives. This project will fill that gap.

What are the goals of the project?

We will generate the first-ever ATAC-Seq data from polar bears. ATAC-Seq is a genomic technique that maps open chromatin, the regions where gene regulatory elements are actively working. We have fat tissue from 3 polar bears from Alaska, collected in 2020. We will also generate ATAC-Seq data from 3 american black bears samples that I collected in 2022 in Florida. Black bears are omnivores like the ancestor polar bears evolved from (”Why not brown bear?” That is a story for backers), so comparing them will reveal which regulatory changes are unique to polar bears. We have preliminary data from comparative genomics showing that polar bears have accelerated regulatory regions near genes involved in fat metabolism, insulin pathways, heart development, but what we want to discover is how those pathways are regulated.

And if you ever talked to a scientist, you know we want to publish EVERYTHING! The data will be publicly available to the scientific community.