Global diversity, recurrent evolution, and recent selection on amylase structural haplotypes in humans

Area of Science:

• Human Evolutionary Genetics
• Genomics
• Nutritional Anthropology

Background:

• The agricultural revolution (~12,000 years ago) shifted human diets towards starch, impacting human evolution.
• Amylase genes (AMY1, AMY2A, AMY2B) are crucial for starch digestion, with copy number variation linked to dietary starch intake.
• Previous evidence for recent selection on amylase gene copy number was limited.

Purpose of the Study:

• To investigate the diversity, evolutionary history, and selective pressures on amylase gene structural variation in humans.
• To analyze the impact of agricultural diets on amylase gene copy number and structure.
• To identify signatures of recent human selection at the amylase locus using advanced sequencing and pangenome approaches.

Main Methods:

• Analysis of 52 long-read diploid assemblies and short-read data from ~5,600 contemporary and ancient humans.
• Identification and characterization of amylase gene structural architectures and copy number variations.
• Application of a pangenome graph-based approach to infer structural haplotypes.
• Examination of 533 ancient human genomes to track frequency changes over 12,000 years.

Main Results:

• Amylase gene copy numbers are higher in populations with agricultural subsistence compared to other subsistence strategies.
• 28 distinct amylase structural architectures were identified, with recurrent evolution of similar structures.
• Duplication-containing amylase haplotypes increased over seven-fold in frequency in West Eurasians over the last 12,000 years.
• Mutation rates for amylase gene duplications/deletions are >10,000-fold higher than the SNP mutation rate.

Conclusions:

• The agricultural revolution drove significant adaptive changes in human amylase gene copy number and structure.
• Long-read sequencing and pangenome approaches are essential for resolving complex structural variations and detecting selection.
• These findings provide strong evidence for recent human adaptation to starch-rich diets driven by agriculture.