Question

I have sequenced roughly 24 genomes from two different continents (Africa and South America), specifically for the envelope gene of yellow fever virus. I used software to generate the dN and dS ratio for each continent

Africa: (dS= 0.2065, dN= 0.0031.) dN/dS ratio= 0.0150

South America: (dS=0.5541, dN= 0.0112.) dN/dS ratio= 0.0202

Im unsure how to interpret these ratio's, and how the difference in the two suggests any differences in the type of selection for the enveloped protein in each continent.

Answer 1

Nucleotide substitutions in genes coding for proteins can be silent synonymous substitution, that do not change the amino acid or non-synonymous substitution that change the amino acid. Usually selection removes non-synonymous substitution. However, under certain Darwanian conditions, they may be retained. Studying number of these synonymous and non-synonymous substitutions indicates degree of selection pressure of a system. Synonymous substitutions give the evolutionary distance between two sequences. Non-synonymous substitutions can be due to positive selection or genetic drift.

Adaptation to environmental conditions induces increased genetic changes at amino acid altering sites than in amino acid–preserving sites in the genome. The ratio of substitution rates at these sites in denoted as dN/dS (S= number of silent synonymous sites, N= number of non-synonymous sites). The ratio dN/dS will be above unity (1) only if positive selection is present stimulating the protein alterations. A ratio less than unity occur only if negative natural selection suppressed protein alterations. If it is 1, no selection has occurred.

This ratio was designed for analysis of genetic sequences from divergent species. When this ratio is applied to samples from single population, it represents polymorphism segregating in this population rather than the representing fixation events along independent lineages.

The dN/dS in this specific problem is among different genomes in different populations. Hence, it is applied to represent fixation events in independent lineages. As both the dN/dS ratios were less than 1, it indicates that natural selection suppressed alternations in the sequences coding for the amino acids sites in the genome. Both the South American and African population sequences were under negative selection, which suppressed the alteration in amino acid sequences.

dN/dS= S/1-e^-S, where S is the selection coefficient. dN/dS ratio for most proteins is between 0.2-0.3.

The dS for the Africa is higher than the dS for South America. There are more synonymous substitutions in Africa than South America. As these substitutions are silent, the coat protein did not change much in Africa as compared to South America.

The dN for South America is higher than for Africa. This indicates there were more non-synonymous substitutions in coat protein sequences in South America. Hence, the coat protein amino acid sequence altered as these substitutions led to change in amino acid sequence, which could be linked to genetic drift.

South America envelope protein sequence was subjected to lesser negative selection than Africa envelope protein sequence in the 24 genomes studied. The selection pressure to conserve the ancestral state is more in Africa than in South America.