NON-CONGRUENT RELATIONSHIPS BETWEEN VARIATION IN EMM GENE-SEQUENCES AND THE POPULATION GENETIC-STRUCTURE OF GROUP-A STREPTOCOCCI

To examine the molecular population genetics of the M protein family o f Streptococcus pyogenes (group A Streptococcus), the 5' regions of po lymerase chain reaction-amplified emm products from 79 M serotypes wer e sequenced and the phylogeny was compared to estimates of overall gen etic relationships among strains determined by multilocus enzyme elect rophoresis. Although the 5' emm sequences from several strains designa ted as distinct M types were identical or almost identical, the overal l pattern is characterized by very extensive variation. The compositio n of distinct emm sequence clusters generally parallels the ability of strains to express serum opacity factor and in some cases historical associations of certain M types with acute rheumatic fever, but not wi th M types classified as nephritogenic. For many strains there is a la ck of congruency between variation in 5' emm sequences and estimates o f overall chromosomal relationships, which is undoubtedly due to horiz ontal transfer and recombination of emm sequences. The results of thes e studies provide insights into the nature and extent of emm sequence variation and describe how this variation 'maps' onto the population g enetic structure of extant S. pyogenes lineages. The complexity of emm sequence and streptococcal cell lineage relationships revealed by thi s analysis has significant implications for understanding evolutionary events generating strain diversity and the epidemiology of S. pyogene s diseases.