EVOLUTION OF A FETAL EXPRESSION PATTERN VIA CIS CHANGES NEAR THE GAMMA-GLOBIN GENE

One basis for the evolution of organisms is the acquisition of new tem poral and spatial domains of gene expression. Such novel expression do mains could be generated either by cis sequence changes that alter the complement of trans-acting regulators binding to control elements or by changes in the expression patterns of one or more of the regulatory (trans) factors themselves. The gamma globin gene is a prime example of a gene that has undergone a distinct change in temporal expression at a defined time in evolution. Approximately 35-55 million years ago, the previously embryonic gamma gene acquired a fetal expression patte rn, This change occurred in a simian primate ancestor after the separa tion of simian and prosimian primates but before the further separatio n of the major simian lineages; thus, the (prosimian) galago gamma gen e retains the ancestral embryonic expression pattern, whereas the (sim ian) human gamma gene is fetal, This analysis of galago and human gamm a genes in transgenic mice demonstrates that cis changes in sequences within a 4.0-kilobase region surrounding the gamma gene were responsib le for the evolution of a novel fetal expression pattern in the gamma globin genes of simian primates.