Assessing DNA sequence variations in human ESTs in a phylogenetic context using high-density oligonucleotide arrays

Area of Science:

• Human evolutionary genetics
• Population genomics
• Molecular anthropology

Background:

• Understanding human genomic diversity is crucial for tracing our evolutionary history.
• Previous studies have suggested varying levels of genetic variation across human populations.
• The role of selection versus neutral processes in shaping human diversity remains an active area of research.

Purpose of the Study:

• To analyze human genomic diversity across four continental populations using expressed sequence tags (ESTs).
• To investigate the mutation rate and test the neutral hypothesis of molecular evolution in humans.
• To estimate the effective population size and understand the partitioning of genetic variation among human populations.

Main Methods:

• DNA resequencing of 898 expressed sequence tags (ESTs) across 32 individuals from four continental populations.
• Analysis of intra-species genetic variation, including segregating sites and nucleotide diversity.
• Estimation of long-term effective population size and partitioning of diversity among continents.

Main Results:

• Human genomic diversity was partitioned among continents, with the highest variation observed in the African sample.
• The mutation rate was lower than expected for unconstrained regions, suggesting selection.
• Africans exhibited higher nucleotide diversity and a greater number of continental-specific polymorphisms, consistent with two distinct lineages and a population bottleneck outside Africa.

Conclusions:

• Human genetic diversity is structured by continental differences, with Africa harboring the most variation.
• The data supports a model of human origins involving two distinct lineages, with subsequent migration and bottlenecks shaping global diversity.
• Selection may play a role in shaping human genomic diversity, alongside neutral evolutionary processes.