Grant: Operating Grant

What makes human different from chimpanzee? Almost all of the phenotypic differences between human and other primates and between human individuals are caused by genetic factors. These genetic factors include differences in protein sequences, the building block of our body, or difference in how genes are regulated, e.g. how much and when and where specific types of protein are made. It is fundamentally important to identify and characterize these genetic factors since they either directly contribute to our "humanness" or cause physiological and morphological differences between human individuals. Such genetic differences between human individuals can often result in difference in disease susceptibility and in response to therapeutic treatments. In this proposal we focus on studying the evolution and genetic variation of one type of genetic regulators: microRNAs. MicroRNAs are a class of small regulatory RNAs that are usually 22 nucleotides long and post-transcriptionally repress their target genes. It is estimated that human genome has 1000 microRNAs and about one-third of the genes are under their regulation. We have identified a list of microRNAs that only arose in the human lineage and are absent in other primates; we will use a combined experimental approach to investigate the genes and biological processes that are regulated by these human-specific microRNAs. We will also apply the same computational and experimental methods on a list of microRNAs who target different genes in different human populations (e.g. Caucasians versus Africans). Such knowledge is very valuable in understanding human genetic variations and in designing and implementation of personalized medicine.