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By I. Kapetanovic

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It is therefore vital that evolutionary principles are applied to the key decision points in the drug development process relating to the validation of targets, hits and lead compounds to minimize the emergence of resistance. 1 What is the possible evolutionary response to drug pressure? Evolution occurs by non-adaptive and adaptive (Darwinian) means. Non-adaptive evolution includes pleiotropic phenomena and genetic drift, or may appear non-adaptive at one level of selection and adaptive at another.

6, 491496, Sharma P (1995). Charak Samhita. Varanasi, India: Chaukambha Orientallia. Steinberg KK, Gwinn M , Khoury MJ (2001). The Role of Genomics in Public Health and Disease Prevention. JAMA: The Journal of the American Medical Association. , 13, 1635, Sumantran VN, Kulkarni A, Chandwaskar R, Harsulkar A, Patwardhan B, Chopra A , Wagh UV (2008). Chondroprotective Potential of Fruit Extracts of Phyllanthus emblica in Osteoarthritis. Evidence-based Complementary and Alternative Medicine. , 3, 329-335, Tripathi J, Reddy KRC, Gupta S , Dubey S (2010).

A simplified substitution rate matrix used by the ML method to estimate codon evolution is given (left). The matrix is used to statistically determine evolutionary pressures acting at individual codons: positive, negative or neutral evolution (see text for more discussion and references below). This model determines the probability that codon i mutates to j in a specified time interval and accounts for the transition/transversion rate ratio (κ); the equilibrium frequency of codon j (πj); and the non-synonymous/synonymous rate ratio (ω).

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