Autophagy Genes and Mammal Longevity

ISEF Category: Cellular and Molecular Biology

Subcategory: Other  ·  Difficulty: Advanced  ·  Setup: University Lab  ·  Time: Full Year

The Hook

Some mammals live 10 times longer than others, even when they are similar in size. That makes lifespan a real clue, not just a trivia fact. If you compare autophagy genes across species, you can ask whether extra copies of those genes line up with extreme longevity.

What Is It?

Autophagy is the cell’s cleanup system. Cells break down old proteins, damaged parts, and other waste, then recycle the pieces. Think of it like a built-in repair crew that keeps a city running instead of letting junk pile up.

ATG genes help control that cleanup process. In this project, you compare those genes across mammal species and ask whether long-lived mammals tend to have more gene duplications in the ATG pathway. A duplication means a gene copy appears more than once in a genome, which can sometimes change how strongly a pathway works or how flexible it is.

You are not proving that one gene causes long life. You are testing whether a pattern exists across many species. That makes the project closer to evolutionary biology and genomics than to a single-gene lab experiment.

Why This Is a Good Topic

This is a strong science fair topic because it gives you a clear hypothesis, public data, and real biological meaning. You can test whether a gene family pattern matches lifespan using species comparisons, which is a classic research move in modern biology. It connects to aging, genome evolution, and cellular quality control, so the topic feels big without needing a wet lab.

Research Questions

• How does the number of ATG-pathway gene duplications relate to maximum lifespan across mammals?
• What is the effect of filtering to only one-to-one orthologs versus all ortholog calls on the duplication-longevity pattern?
• Does the correlation between ATG copy number and lifespan remain after controlling for body mass?
• To what extent do bats, whales, and naked mole-rat-like long-lived mammals differ from other mammals in ATG gene copy patterns?
• Which ATG genes show the strongest association with lifespan when each gene is tested separately?
• How does the result change when you compare duplication counts against log-transformed lifespan values?

Basic Materials

• Computer with internet access and enough storage for downloaded tables.
• Spreadsheet software such as Google Sheets or Excel.
• PubMed access for background reading.
• Ensembl genome browser for ortholog and gene family data.
• AnAge database for mammal lifespan data.
• A reference list of mammal species matched across both databases.

Advanced Materials

• Computer with Python installed.
• Jupyter Notebook or RStudio for data cleaning and analysis.
• Biopython or pandas for table handling.
• R packages such as ape and phytools for phylogenetic analysis.
• Access to Ensembl BioMart or Ensembl Compara downloads.
• A species phylogeny file for comparative methods.
• PubMed and review articles on autophagy, aging, and mammal comparative genomics.

Software & Tools

• Ensembl BioMart: Helps you export ortholog and gene family tables for the ATG genes you want to compare.
• AnAge: Provides maximum lifespan and life history data for mammal species.
• Google Sheets: Lets you clean a species list and make a first-pass correlation plot.
• Python: Helps you merge species tables, calculate statistics, and automate data checks.
• RStudio: Supports comparative analyses and phylogenetic plots when you move beyond simple correlations.

Experiment Steps

1. Define the exact ATG gene set you will study, and decide whether you are comparing the whole pathway or a smaller gene subset.
2. Match species between Ensembl and AnAge, then make a clean master table with lifespan, body mass, and gene copy information.
3. Choose your main outcome metric, such as total ATG duplication count or duplication count per gene, and decide how you will normalize it.
4. Plan a comparison that tests your idea against a confounder like body size or phylogenetic relatedness, not just raw lifespan.
5. Build a simple analysis pipeline that can screen each gene, plot the species pattern, and flag outliers.
6. Decide what result would count as support, weak support, or no support for your hypothesis before you look at the final statistics.

Common Pitfalls

• Mixing species names across databases, which creates false mismatches and drops good data.
• Treating every gene copy as a true duplication without checking whether the database call reflects annotation noise.
• Comparing raw lifespan values without adjusting for body size, which can make large mammals look special for the wrong reason.
• Ignoring phylogenetic relatedness, which can make closely related species look like many independent data points.
• Testing too many genes and then calling the first positive result meaningful, which inflates false discovery.

What Makes This Competitive

A stronger version of this project goes beyond a simple correlation. You can control for body mass, lifespan, and shared ancestry, then test whether the pattern still holds. You can also compare several ATG genes instead of reporting one favorite hit. If you add a clean phylogenetic method, a sensitivity analysis, and a clear reason for why specific long-lived mammals matter, the project starts to feel like real comparative genomics.

Project Variations

• Compare ATG gene copy number in bats versus non-flying mammals with similar body sizes.
• Test whether autophagy gene duplications are stronger in long-lived rodents than in short-lived rodents.
• Replace duplication counts with sequence conservation scores to ask whether long-lived mammals keep ATG genes under stronger constraint.

Learn More

• Ensembl: Search the Ensembl BioMart and ortholog documentation for mammal gene family data.
• AnAge: Search the AnAge database for maximum lifespan records and species life history tables.
• NCBI PubMed: Search for review articles on autophagy, aging, and comparative genomics.
• NIH NCBI Bookshelf: Look for free book chapters on autophagy and cell maintenance.
• MIT OpenCourseWare: Search for free biology and genomics course materials that explain orthologs, phylogeny, and sequence comparison.
• Annual Review of Genomics and Human Genetics: Search this journal for review articles on genome evolution and aging.