targeting multiple characters. Some of these highly differentiated populations have also been selected "backward" or "in reverse," by returning experimental populations to their ancestral culture regime. Hundreds of people have worked with these populations over the better part of three decades. Much of this work is summarized in the papers collected in the book Methuselah Flies. The early experiments in flies were limited to studying phenotypes but the molecular mechanisms, i.e., changes in DNA that facilitated such changes, could not be identified. This changed with genomics technology. Subsequently, Thomas Turner coined the term Evolve and Resequence (E&R) and several studies used E&R approach with mixed success. One of the more interesting experimental evolution studies was conducted by Gabriel Haddad's group at UC San Diego, where Haddad and colleagues evolved flies to adapt to low oxygen environments, also known as hypoxia. After 200 generations, they used E&R approach to identify genomic regions that were selected by natural selection in the hypoxia adapted flies. More recent experiments are following up E&R predictions with RNAseq and genetic crosses. Such efforts in combining E&R with experimental validations should be powerful in identifying genes that regulate adaptation in flies. Microbes Many microbial species have short generation times, easily sequenced genomes, and well-understood biology. They are therefore commonly used for experimental evolution studies. The bacterial species most commonly used for experimental evolution include P. fluorescens, Pseudomonas aeruginosa, Enterococcus faecalis and E. coli (see below), while the Yeast S. cerevisiae has been used as a model for the study of eukaryotic evolution. Lenski's E. coli experiment One of the most widely known examples of laboratory bacterial evolution is the long-term E.coli experiment of Richard Lenski. On February 24, 1988, Lenski started growing twelve lineages of E. coli under identical growth conditions. When one of the populations evolved the ability to aerobically metabolize citrate from the growth medium and showed greatly increased growth, this provided a dramatic observation of evolution in action. The experiment continues to this day, and is now the longest-running (in terms of generations) controlled evolution experiment ever undertaken. Since the inception of the experiment, the bacteria have grown for more than 60,000 generations. Lenski and colleagues regularly publish updates on the status of the experiments. Leishmania donovani Bussotti and collaborators isolated amastigotes from Leishmania donovani and cultured them in vitro for 3800 generations (36 weeks). The culture of these parasites showed how they adapted