Understanding the evolution of continuous genomes

Introduction

An organism's phenotype depends on a multitude of genetic variants, spread over a linear genome. This is widely understood, and yet in practice, has hardly been incorporated into population genetic analysis. Recent developments in theory, computation, and sequencing technology now make it possible to obtain and analyze whole haploid genomes on a large scale.

Project Objectives

This proposal is to develop and apply a theoretical analysis of genetic variation that is spread over continuous linear genomes. Theory and methods will be developed in close interaction with empirical data from:

1. Artificial selection experiments
2. An intensely studied hybrid zone in Antirrhinum

For both, we have a known pedigree and phased whole-genome sequence.

Methodology

Population structure will be analyzed by:

• Following blocks of genome through pedigrees
• Analyzing across two-dimensional landscapes

Selection on discrete loci will be analyzed by:

• Finding its effect on surrounding haplotypes
• Analyzing how favored alleles become disentangled from heterogeneous backgrounds
• Observing how haplotype blocks flow past selected clines

Modeling Contributions

The contribution of variants that are spread across the genome to:

• Genome-wide association studies (GWA)
• Selection response
• Hybrid zones

will be modeled. The overall effect of inherited fitness variance on haplotype structure will be determined.

Impact

This work will establish a new framework for population genomics that goes beyond the current focus on individual loci. It will help bridge the distinct communities within genomics, quantitative genetics, and population genetics, which currently tackle these problems largely in isolation.

Conclusion

The project will develop better tools for inferring selection and population structure from DNA sequence data. More fundamentally, it will give us a deeper understanding of how the abundant variation that is carried on linear genomes is shaped by evolution.