If you recall from Y Chromosome II, the ampliconic class displays extraordinarily high sequence similarity to other sequences of the same region, has higher gene density than the X-degenerate class, and its genes are found in multiple copies and are expressed almost exclusively in the testes. The ampliconic class just doesn’t show the signs of gene decay like the rest of the male-specific Y chromosome. Why?
Skaletsky et al. (2003) argue that the ampliconic class does not fit in the strata model discussed in Y Chromosome III. Instead, they believe that multiple molecular mechanisms explain the translocation of now ampliconic genes from the autosomes. For example, DAZ was transposed from DAZL (on chromosome 3) and subsequently duplicated on the Y; and CDY resulted from the retrotransposition of processed mRNA (since it lacks introns) derived from its autosomal counterpart.
Skaletsky et al. (2003) additionally believe that sexual antagonism (discussed in Y Chromosome IV) accounts for the movement of ampliconic genes from autosomes to the sex chromsomes. However, as we saw in the previous post, sexual antagonism isn’t a sure bet, as argued by Jennifer Graves.
Jennifer Graves (2004) criticizes the genomic niche hypothesis. She does not think the X-degenerate and ampliconic sequences have different evolutionary origins nor are the differences between them as stark as others have claimed. She argues that several of the so-called ampliconic genes are actually derived from the ubiquitously expressed X-linked genes (SRY, TSPY, and RBMY) and that ZFY, a ubiquitously expressed single copy gene (X-degenerate) in humans is testis-specific and amplified (ampliconic) in mice.
A study by Bhowmick et al. (2007) confirms Graves’ argument. Bhowmick et al. examined the origins of the ampliconic genes and whether or not their divergence agrees with the “evolutionary strata” theory by using phylogenetic analysis and KS calculations. For example, there are eight copies of XKRY, an X homologue XKRX, and an autosomal homologue XKRLY. In the compiled tree (Figure 1), XKRX and XKRY/XKRYL form two monophyletic clusters, indicating that XKRX and XKRY have been differentiating longer than XKRY and XKRYL. Furthermore, synonymous site divergence between XKRX and XKRY is Ks = 1.128 ± 0.236, placing it in stratum 1 (Table 1 of Y Chromosome III), consistent with the results from the Page lab. Bhowmick et al. suggest that XKRX/XKRY were on the proto-X/Y autosomes and after XY differentiation, a copy of XKRY was transposed to an autosome creating XKRYL.
Continuing this analysis for VCY, HSFY, RBMY, and TSPY, Bhowmick et al. conclude that these gene families originated on the proto-XY, began diverging as recombination was suppressed along the Y chromosome, and later gained their sex-specific ampliconic features. Thus Skaletsky et al.’s proposal of ampliconic genes having a “genomic niche” is likely refuted for five of the nine ampliconic genes – these genes were on the sex chromosomes already and their autosomal homologues were transposed post-XY-divergence. The proposal may still hold for DAZ and CDY, as they were transposed to the Y after XY divergence, and two other gene families weren’t considered (BPY and PRY). This also doesn’t mean that the genes weren’t duplicated because of the pressures of sexual reproduction, just that the genes didn’t move to the Y because of sexual antagonism.
If sexual antagonism doesn’t explain the ampliconic region, what can? Why don’t the ampliconic sequences show the signs of decay the X-degenerate sequences do? There is a very interesting hypothesis that has been gaining traction since at least 2003 and is still being worked out as I write. The hypothesis also changes how we see the Y chromosome – perhaps it isn’t as static and isolated as previously thought! I am still working out how it all works so you should most likely expect the post sometime next week. Stay tuned!
Bhowmick BK, Satta Y, & Takahata N (2007). The origin and evolution of human ampliconic gene families and ampliconic structure. Genome research, 17 (4), 441-50 PMID: 17185645
Graves JA (2004). The degenerate Y chromosome–can conversion save it? Reproduction, fertility, and development, 16 (5), 527-34 PMID: 15367368
Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, Repping S, Pyntikova T, Ali J, Bieri T, Chinwalla A, Delehaunty A, Delehaunty K, Du H, Fewell G, Fulton L, Fulton R, Graves T, Hou SF, Latrielle P, Leonard S, Mardis E, Maupin R, McPherson J, Miner T, Nash W, Nguyen C, Ozersky P, Pepin K, Rock S, Rohlfing T, Scott K, Schultz B, Strong C, Tin-Wollam A, Yang SP, Waterston RH, Wilson RK, Rozen S, & Page DC (2003). The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature, 423 (6942), 825-37 PMID: 12815422