Natural Selection Analysis: Part1
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This document provides an overview of natural selection analysis and methods for measuring natural selection through analyzing DNA sequences. It discusses three main types of natural selection - positive selection which favors beneficial mutations, negative selection which removes detrimental mutations, and balancing selection which maintains genetic variation. It then focuses on explaining the dN/dS ratio test, one of the most widely used methods for detecting natural selection. The dN/dS ratio compares the rate of non-synonymous substitutions that change the protein sequence to the rate of synonymous substitutions that do not change the protein sequence. Different dN/dS ratios can indicate if a sequence is experiencing neutral evolution, negative selection, or positive selection.
Natural Selection Analysis: Part1
- 1. Lab#10: Natural Selection Analysis Asian University For Women BINF 2000: Introduction to Bioinformatics (Lab - Fall 2022) Syed Mohammad Lokman Instructor Asian University for Women
- 2. Selection Analysis: Objective ● attempts to identify if natural selection is acting on DNA sequences ● if natural selection is indeed acting, ○ is the selection “positive” or “negative”, i.e. is there selection for or against a site?
- 3. Natural selection: Type ● Positive (“Darwinian”) selection occurs when a beneficial mutation arises in a population and increases in frequency (e.g. antibiotic resistance) ● Negative (purifying) selection is the obverse of positive selection. It occurs when a detrimental mutation is selected out of a population. ● Balancing or diversifying selection is selection that favours the maintenance of genetic variation at a locus multiple environments select for different allelic forms of a protein.
- 4. Measuring selection: ● There are two commonly used measures: ○ 1. Tajima’s D and ○ 2. the dN/dS test
- 5. dN/dS ratio test for selection: ● The dN/dS (also known as Ka/Ks) Ratio Test is perhaps the most widely used method for detecting the pattern of natural selection from nucleotide sequence data. ● This test is particularly useful because it can infer selection acting all the way down to the level of the codon: ○ are there specific sites that are being selected for?
- 6. Non-synonymous versus synonymous nucleotide changes: ● Non-synonymous substitutions result in a change in the protein sequence ● Synonymous substitutions change the DNA sequence, but not the protein sequence due to the degeneracy of the genetic code
- 7. The Degeneracy of the Genetic Code:
- 8. The dN/dS ratio test: ● dN = the number of non-synonymous substitutions per non-synonymous site ● dS = the number of synonymous substitutions per synonymous site ● Calculates the ratio of the rate of non-synonymous substitutions (dN) to the rate of synonymous substitutions (dS).
- 9. The dN/dS ratio test: ● Synonymous substitutions are not exposed to (strong) selective pressures since they don’t result in a change to the protein sequence ● they tend to accumulate at roughly a constant rate, ○ Hence, can be used as a baseline to compare the rate of substitutions that change the protein sequence, i.e. non-synonymous substitutions.
- 10. Interpretation of dN/dS ratio: ● In the case of a completely neutral sequence (one that is free to change with no constraints), you would expect dN to be the same as dS, or dN/dS = 1 ● When there are selective constraints on a sequence (negative selection), you would expect fewer substitutions that change the protein sequence, or a lower dN dN/dS < 1 ● • In the case of positive selection, you would expect to see a higher proportion of amino acid substitutions in your population (because they are being increased by positive selection), so a higher dN dN/dS > 1
- 18. Ref: Khateeb, J., Li, Y. & Zhang, H. Emerging SARS-CoV-2 variants of concern and potential intervention approaches. Crit Care 25, 244 (2021). https://doi.org/10.1186/s13054-021-03662-x
- 19. (a) The perception of a microbe-associated molecular pattern (MAMP) (indicated by dashed lines coming off the bacterial flagella) by plant membrane bound receptors induces a basal defense response, which ultimately results in MAMP-triggered immunity. (b) Bacterial pathogens respond by secreting and translocating T3SEs, which target and disrupt the basal defense-signaling pathway and/or host proteins referred to as virulence targets. The disruption of basal defense signaling results in T3SE-mediated susceptibility and disease. (c) Plant hosts respond to T3SEs through the action of R proteins, which monitor virulence targets. When R proteins detect a pathogen-associated change, they induce an R protein-mediated defense response, which results in T3SE-triggered immunity. (d) Pathogens may translocate additional T3SEs that specifically target and suppress the R protein mediated defense response, thereby restoring host susceptibility and disease. Ref: McCann, H.C. and Guttman, D.S. (2008), Evolution of the type III secretion system and its effectors in plant–microbe interactions. New Phytologist, 177: 33-47.
- 20. Thank You