Extensive studies on human genes reveal that along with many non-disease genes human genomes also contain a fraction of genes that are linked with several hereditary diseases. Mendelian genetics has been extraordinarily successful in the elucidation of monogenic diseases (affecting single gene), however, polygenic diseases (affecting multiple genes) do not follow the Mendelian pattern of inheritance. Understanding the factors causing differences in the evolutionary rates of proteins have always been a study of interest. Investigation on the molecular genetics of disease genes raises a key question why severe mutations often do not result in a detectable abnormal phenotype? Previous reports illustrate the contribution of gene duplicates to back-up against deleterious human mutation. Exploring the factors determining protein evolutionary rate and elucidation of the genetic robustness against deleterious mutations are the important objectives of this project.

For a long time, the central issue of evolutionary genomics was to find out the adaptive strategy of nucleic acid molecules having different optimal growth temperatures (Topt). Long-standing controversies exist regarding the correlations between genomic G + C content and Topt. We are working to find the evolutionary forces for temperature adaptation of DNA and RNA molecules by comparing large number of genome sequences having widely different growth temperatures.

3. Evolutionary perspectives of synonymous codon usage analysis.

Translation code is redundant at the RNA level and several codons can code for the same amino acid and are therefore called synonymous. Contrary to expectations of codon usage being random (or unbiased), it is actually biased and there are definite evidences of selective forces dictating biased codon usage. Maintenance of translational accuracy and efficiency, variations in tRNA availabilities and/or variations in codon-anticodon binding have been offered as possible causes for codon bias. We have detected several new factors in determining the non-random synonymous codon usage and at present we are interested to see the context dependent codon bias. Evolution of amino-acid sequences is inextricably linked to the evolution of synonymous coding sites (which affect translational efficiency and mRNA stability). The structure and stability of proteins affects their overall evolutionary rate. To detect the role of codon pair contextual effects in maintaining translation accuracy and speed is the major objective of this project.