Multiple substitutions Multiple substitutions take place when single nucleotides undergo multiple changes before reaching their final nucleotide identity. A sequence is said to be saturated because mutation has acted multiple times upon nucleotides and observed change in sequence is, in fact, less than the historical change in sequence. Genetic saturation can also be estimated by comparing the number of observed differences in nucleotide sequences between multiple pairs of species. The number of observed substitutions between sequences of different species can be compared to the number of inferred substitutions based on branch length to find the approximate point where the number of inferred substitutions surpasses the number of observed substitutions. This method can give researchers an idea of the level of saturation of a particular gene but is thought to underestimate the amount of saturation, especially for very large branch lengths.
Impact on phylogenetics In the field of
molecular phylogenetics, the distances and relationships between species are investigated by looking at the DNA, RNA or amino acid sequences of an organism. When phylogenetic trees are constructed without considering possible saturation, the possibility of multiple substitutions can cause the distance between taxa to appear much smaller than the true distance.
Multiple sequence alignment, a common technique to construct phylogenies, relies on the comparison of homologous sequences. It can easily be confounded by genetic saturation because the homologous loci under investigation show no indication whether or not more than one substitution on each nucleotide separates the taxa being described. Furthermore, saturation effects can lead to a gross underestimation of divergence time. This is mainly attributed to the randomization of the phylogenetic signal with the number of observed sequence mutations and substitutions. The effects of saturation can mask the true amount of divergence time leading to inaccurate phylogenetic trees.
The principle of parsimony in genetic saturation analysis Parsimony plays a fundamental role in genetic saturation analysis. This principle gives preference to the simplest explanation that can explain the data. In regards to genetic saturation, parsimony means that the hypothesized relationship is one that has the smallest number of character changes. Using parsimony to analyze genetic saturation can lead to conflict when creating a phylogenetic tree. When only sequence data is used, it is possible to come up with numerous phylogenetic trees with the same amount of parsimony.
Long branch attraction Genetic saturation contributes to long-branch attraction in its ability to greatly mix up
genetic code without easily observable associated phenotypic changes.
Long branch attraction occurs when two relatively
outgrouped taxa are seemingly closely linked. The more substitution mutations, the more likely it is for previously dissimilar sequences to share nucleotides and as a result, show homology in phylogenetic tree calculations. Long-branch attraction due to saturation has been proposed to be the cause of links in ancient phylogenies and puts into question even some of the earliest relationships between
eukaryotes,
archaea, and
eubacteria. ==Other uses of "Saturation" in genetics==