ANALYSIS OF MUTATION-RATES IN THE SMCY SMCX GENES SHOWS THAT MAMMALIAN EVOLUTION IS MALE DRIVEN/

Mammalian evolution is believed to be male driven because the greater number of germ cell divisions per generation in males increases the op portunity for errors in DNA replication. Since the Y Chromosome (Chr) replicates exclusively in males, its genes should also evolve faster t han X or autosomal genes. In addition, estimating the overall male-to- female mutation ratio (alpha(m)) is of great importance as a large alp ha(m) implies that replication-independent mutagenic events play a rel atively small role in evolution. A small alpha(m) suggests that the im pact of these factors may, in fact, be significant. In order to addres s this problem, we have analyzed the rates of evolution in the homolog ous X-Y common SMCX/SMCY genes from three different species-mouse, hum an, and horse. The SMC genes were chosen because the X and Y copies ar e highly homologous, well conserved in evolution, and in all probabili ty functionally interchangeable. Sequence comparisons and analysis of synonymous substitutions in approximately 1 kb of the 5' coding region of the SMC genes reveal that the Y-linked copies are evolving approxi mately 1.8 times faster than their X homologs. The male-to-female muta tion ratio alpha(m) was estimated to be 3. These data support the hypo thesis that mammalian evolution is male driven. However, the ratio val ue is far smaller than suggested in earlier works, implying significan ce of replication-independent mutagenic events in evolution.