Positive Selection and the dN/dS Ratio: Interpreting Evidence from Molecular Evolution

In the field of molecular evolution, scientists use genetic data to uncover the forces shaping the diversity of life. One of the most powerful tools for detecting natural selection at the molecular level is the comparison of non-synonymous (amino acid-changing) and synonymous (silent) substitutions in protein-coding genes. The ratio of these two types of substitutions, known as the dN/dS ratio, provides crucial insights into the evolutionary pressures acting on genes.

What Are Non-Synonymous and Synonymous Substitutions?

• Non-synonymous substitutions alter the amino acid sequence of a protein, potentially affecting its function.

• Synonymous substitutions do not change the amino acid sequence and are generally considered neutral with respect to selection.

The dN/dS Ratio Explained

• dN: Rate of non-synonymous substitutions per non-synonymous site.

• dS: Rate of synonymous substitutions per synonymous site.

• dN/dS ratio: A key metric for assessing the type of selection acting on a gene.

Interpreting the dN/dS Ratio

• dN/dS < 1: Indicates purifying (negative) selection, where most amino acid changes are deleterious and removed by selection.

• dN/dS ≈ 1: Suggests neutral evolution, where amino acid changes are neither favored nor disfavored.

• dN/dS > 1: Provides strong evidence for positive selection, where amino acid changes are advantageous and increase in frequency within a population1356.

Evidence from Research

Studies have consistently shown that a dN/dS ratio greater than one is a hallmark of positive selection, meaning that the gene is evolving rapidly due to the adaptive advantage conferred by amino acid changes56. This pattern is often observed in genes involved in immune response, reproduction, and adaptation to new environments.

Conclusion: What Does a dN/dS Ratio Greater Than One Mean?

If the ratio of non-synonymous to synonymous substitutions per site in a protein-coding gene is greater than one, it is clear evidence of positive selection acting on that gene. This indicates that natural selection is favoring changes in the protein sequence, driving evolutionary innovation.

Correct answer:
(1) positive.