The natural selection that shapes our genomes

Area of Science:

• Human genomics
• Population genetics
• Evolutionary biology

Background:

• Purifying selection and GC-biased gene conversion constrain approximately 95% of human genome variation.
• Utilizing non-neutral genetic variation for demographic inference can introduce biases, impacting estimates like the time to the most recent common ancestor.
• Previous studies have primarily focused on specific genomic regions or variant types.

Purpose of the Study:

• To re-evaluate the utility of neutral genetic variation for human population and forensic genetic studies.
• To assess the impact of using non-neutral versus neutral variation on demographic and ancestry estimations.
• To investigate the functional and genomic distribution of neutral variation in the human genome.

Main Methods:

• Analysis of entire human genomes from The 1000 Genomes Project.
• Examination of the distribution of neutral genetic variation across genomic features (exons, introns).
• Comparison of biogeographical ancestry estimates derived from neutral single nucleotide polymorphisms (SNPs) versus non-neutral SNPs.

Main Results:

• Approximately 99% of neutral human genome variation lacks exonic function.
• About 35% of neutral variation is located within introns.
• Biogeographical ancestry estimates derived from non-neutral SNPs show minimal differences compared to those from neutral variation.

Conclusions:

• The majority of human genome variation is under constraint, with neutral variation largely residing outside of exons.
• Current methods for demographic and ancestry inference may not significantly benefit from the exclusive use of non-neutral variation.
• Further research is warranted to refine the use of genetic variation in human population and forensic genetics.