Recurrent evolution and selection shape structural diversity at the amylase locus

Area of Science:

• Human Evolutionary Genetics
• Genomics
• Archaeological Science

Background:

• The shift to agriculture dramatically altered human diets, increasing reliance on starch.
• Amylase genes are crucial for starch digestion, with copy number variations linked to dietary habits.
• Previous evidence for recent selection on amylase gene copy number was limited.

Purpose of the Study:

• To investigate the diversity and evolutionary history of structural variations at the amylase locus.
• To understand the impact of the agricultural revolution on human amylase gene copy number.
• To identify evidence of selection acting on amylase gene structural variation.

Main Methods:

• Analysis of 94 long-read haplotype-resolved assemblies and ~5,600 short-read human genome data (contemporary and ancient).
• Pangenome-based approach to infer structural haplotypes across diverse human populations.
• Leveraging 533 ancient human genomes to track haplotype frequency changes over 12,000 years.

Main Results:

• Identified 28 distinct amylase gene structural architectures, with recurrent evolution of similar structures.
• Agricultural populations exhibit higher amylase gene copy numbers compared to non-agricultural groups.
• Duplication-containing haplotypes, associated with increased gene copies, rapidly rose in frequency in West Eurasians over the past 12,000 years.

Conclusions:

• Human amylase gene copy number and structure have undergone significant adaptation since the agricultural revolution.
• Structural variation at the amylase locus shows strong signals of positive selection in response to dietary changes.
• This study underscores the role of structural variation in human adaptation to major lifestyle shifts.