Unbelievable Y chromosome differences between humans and chimpanzees

Holy crap!

Indeed, at 6 million years of separation, the difference in MSY gene content in chimpanzee and human is more comparable to the difference in autosomal gene content in chicken and human, at 310 million years of separation.

So much for 98 percent. Let me just repeat part of that: humans and chimpanzees, "comparable to the difference ... in chicken and human".

This is from a new paper that's just shown up in the Nature advance publication zone. The authors are Jennifer Hughes and colleagues, and the subject is the first complete sequencing of the chimpanzee Y chromosome. "MSY" stands for "male-specific region of the Y chromosome" -- it's most of the Y, aside from a small fraction that recombines with the X chromosome.

The Y chromosome was part of the initial chimpanzee genome draft, and was recognized then as a "clear outlier" in showing low human-chimpanzee sequence similarity (Chimpanzee Genome Consortium 2005). But it wasn't obvious just how different it was because the relatively short sequencing reads aligned fairly well with the human draft. That comparison also seems not to have included the missing genes (they might have just been missed during sequencing), or duplications. Moreover, the Y chromosome includes a high fraction of repetitive sequence, including long front-to-back, or "palindromic" passages. Only with very long reads with long overlaps is it possible to straighten out the large-scale sequence, and thereby detect sequence reorganizations and large copy number variants. This kind of intensive sequencing has so far been completed only for chromosome 21 and now the Y chromosome.

I can't believe how sedated the reaction to this paper has been so far. The outcome of the sequencing is really, really weird. More than thirty percent of the chimpanzee Y chromosome has no homolog in humans, and likewise for the human Y in chimpanzees.

I mean, really -- here's a map:

Chimpanzee compared to human Y chromosome

Just glancing at the ideograms, they don't even look like homologous chromosomes!

Obviously they are; there's a whole lot of homologous sequence in there including functional genes. But the structure of both human and chimpanzee Y chromosomes has evolved incredibly fast compared to the rest of the genome.

The central question: beyond its interest for Y chromosome structural evolution, what does this result say about the evolution of human (and chimpanzee) phenotypes?

Option 1: Maybe nothing. The main mechanism for the rapid structural evolution was probably autologous recombination. Imagine that the Y chromosome wriggles around and different copies of repetitive sequences get together with each other.

The molecular mechanisms that enabled this wholesale remodelling of ampliconic regions merit consideration. Although the chimpanzee and human MSYs do not normally participate in meiotic exchange with a partner chromosome, the mirroring of sequences in the ampliconic regions provides ample opportunity for ectopic homologous recombination within the MSY. This recombinational proclivity is well documented in the human MSY, where it has repeatedly given rise to large-scale structural polymorphisms during the past 100,000 years of human history as well as to Y-chromosomal anomalies that cause spermatogenic failure and sex reversal in current generations. We suggest that ectopic homologous recombination between MSY amplicons has similarly accelerated structural remodelling of the MSY in the chimpanzee and human lineages during the past 6 million years.

That leads to rapid structural evolution, but not necessarily any functional changes.

Option 2: Massive changes in gene regulation. Then again, widespread relocations of genes have a way of stripping them apart from upstream (or downstream) elements that may regulate their expression. Besides that, chimpanzees have lost several genes entirely, while humans have picked up a few that weren't in the common ancestor. So there's a potential for phenotypic evolution from these changes, possibly reverberating through the genome.

In aggregate, the consequence of gene loss and gain in the chimpanzee and human lineages, respectively, is that the chimpanzee MSY contains only two-thirds as many distinct genes or gene families as the human MSY, and only half as many protein-coding transcription units.

That's pretty amazing. They speculate that the most important phenotypic correlates of these genetic changes may be related to sperm or testicular function, which certainly is a target of rapid evolution elsewhere in the chimpanzee and human genomes.

Option 3: Hitchhiking. OK, this isn't different or mutually exclusive from the above, but it's worth remembering that it only takes a single advantageous mutation to fix the entire Y chromosome in the population. That event carries with it whatever strange mutations might be on the same copy as the initial advantageous change. This kind of event may have happened dozens or even hundreds of times on the chimpanzee and human lineages. Indeed, if it was common enough, hitchhiking can drive its own dynamic, since it tends to fix lots of slightly deleterious variations that later have to be repaired or accommodated.

An interesting possibility: Maybe the extreme evolution of the Y chromosome in the emerging human and chimpanzee lineages explains the unusual similarity of their X chromosomes.

I'm thinking back to the story about chumans and the divergence of chimpanzee and human lineages ("The dawn chumans"). Patterson and colleagues (2006) suggested that the two lineages had undergone some kind of hybridization event long after they began to diverge. This surprising hypothesis was meant to explain why the X chromosome shows a substantially lower level of genetic difference between humans and chimpanzees, compared to the average autosomal locus. I don't think that a late hybridization is necessary to account for X chromosome similarity. A large ancestral effective population size implies a wide variance in coalescence times in the ancestral population; the average on the X will be lower than the autosomes, and if there was any hitchhiking the X would be lower still.

But...that X chromosome similarity might have a different explanation. A fraction of the human Y chromosome continues to recombine with the X. Imagine an initially rapid divergence of Y chromosomes within the chuman population. For a while, there might have been a strong selection pressure on the ancestral X to equip it for the structural diversity of the Y. Possibly an inverse relation would have emerged: the as the Y becomes variable (possibly in partially isolated subpopulations), the X adapts to that variation until reproductive isolation finally occurs.

Could this have been the proximate cause of human-chimpanzee reproductive isolation? The sex chromosomes are often implicated in speciation through Haldane's rule. It's a bit of speculation, but not too far from some discussion within the paper, particularly the relation between Y chromosome variations and infertility.

References:

Hughes JF and 16 others. 2010. Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content. Nature (early online) doi:10.1038/nature08700