Is selection responsible for the low level of variation in the last intronof the ZFY locus?

DNA variability was investigated in the last intron of the Y-chromosome-spe cific zinc finger gene, ZFY, and its X homolog on Xp21.3, ZFX. No polymorph isms were found in the 676-bp ZFY segment in a sample of 205 worldwide-dist ributed Y chromosomes, other than a solitary nucleotide variant in one indi vidual (nucleotide diversity rr = 0.0014%). In contrast, 10 segregating sit es (pi = 0.082%) were identified within 1,089 bp of the ZFX sequence in a s ample of 336 X chromosomes. Four of these polymorphisms, which contributed most of the diversity, were located within an Alu insert disrupting the ZFY -ZFX homology ( pi(Alu) = 0.24%). The diversity in the homologous portion o f the ZFX intron, although higher than that in ZEY, was lower than that fou nd in genomic segments believed to evolve neutrally; interspecies divergenc e in both segments was also reduced. Although this suggests that the evolut ion of both ZFY and ZFX homologs may not be entirely neutral, both Tajima a nd HKA tests did not reject neutrality. The lack of statistical significanc e may be attributed to a lack of power in these tests (the low divergence a nd variability values reduce the power of the HKA and Tajima tests, respect ively); furthermore, Homo sapiens has recently undergone a rapid population growth, and selection is more difficult to detect in an expanding populati on. Therefore, the failure to reject neutrality does not necessarily indica te the absence of selection. In this context, the phylogenetic argument was given more weight in our interpretations. The high level of sequence ident ity in ZFY and ZFX segments, in spite of their separation 80-130 MYA, refle cts a lower mutation rate as compared with other segments believed to under go unconstrained evolution. Thus, the possibility of weak selection contrib uting to the low level of nucleotide diversity in the last ZFY intron canno t be excluded and should be kept in mind in the population genetics studies based on Y chromosome variability.