Two whole genome duplications lie at the root of vertebrate evolution.
Another week, another story about the power of gene duplication in evolution. While rare during normal reproduction, gene duplication happens pretty frequently over longer time scales. How else would we get a thousand olfactory receptor genes, all similar to each other? But other accidents can occur as well, like whole chromosome duplications (such as what leads to Down syndrome), and whole genome duplication, when the cell division process stops early, but otherwise proceeds with cells remaining viable with double the genomes as before. This is common in plants. Corn is tetraploid, wheat is hexaploid, and strawberries are octaploid.
But among animals, whole genome duplication is less common. Two decades ago, however, two researchers working from the newly sequenced human genome revealed that there were two such duplication events at the beginning of vertebrate evolution, explaining some oddities and also perhaps the speed and power of subsequent evolution. The basic evidence is the genome sequence, which is full of related genes. Genes that do the same thing in various species, and are lineally related, are called orthologs. That is relatively simple, per the Darwinian tree of descent of all life. Genes within one organism / one genome that are similar to each other due to ancient duplication events are called paralogs. All those olfactory receptors are paralogs, for instance. Lastly, genes that are paralogs stemming from a whole-genome duplication event are called ohnologs, in honor of Susumu Ohno, who led the field of molecular evolution in recognizing the importance of gene duplication, and speculated about whole genome duplication well before it was discovered.
A classic example of this evidence is the hox cluster, a linear sequence of genes that have been extensively studied in flies as providing an important set of regulatory controls over the linear body plan. They lie in the middle of the developmental cascade, downstream of egg and body polarity genes, but upstream of specific appendage and tissue expression programs. They encode DNA-binding (homeobox) transcription regulators, and their position in the genome is co-linear with the body parts they activate because there is a progressive chromatin opening process by which this whole locus becomes activated. Well, flies have one hox locus, but vertebrates have four. What happened?
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| Hox loci across evolution. Where flies and primitive chordates have one hox cluster, vertebrates have four. How did that happen? |
Obviously, once researchers lined everything up, it became pretty clear that there were two massive duplications along the way, creating four hox loci in the genome, after which quite a few of the duplicated genes fell away. After a duplication event, gene survival is a race between neo-functionalization (which leads to preservation by selection) and deleterious mutation, degradation, and disposal. Enough of these ohnologs survived to help fuel the substantially greater complexity of the vertebrate body plan, now including intricate wrists and hands, and ever more involved head structures.
Similar findings were made all over the human genome. The original paper has a graph that shows that, across the genome, most paralogs exist in families of four. If genome duplication were not the applicable hypothesis, then one would expect a smooth asymptotic curve downwards from one member (implicit) to two, then three, and fewer from there outwards, since single gene duplications would each be independent statistical events. But no, there is a peak at four, indicating that some process yoked together many, many genes into parallel duplication events, twice in succession.
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| A graph of count of paralogs vs their frequency by count, in the human genome. What should in principle have been a smoothly declining curve from 1 or 2 turned out to have a weird peak at the number four. This was important evidence that many of our paralogs arose through some common event, such as a pair of ancient whole genome duplications. |
OK, so far, so old hat. A bunch of more recent papers flesh out this story a bit, showing how the vertebrate duplications were timed, and how they affected various types of genes. miRNAs, for instance, turn out to be ancient genetic elements, and were duplicated along with everything else. miRNAs that originate from (and were preserved from) the whole genome duplications tend to be more conserved, have more targets than other miRNAs, are more highly expressed, and have higher rates of targeting RNAs of transcription regulatory proteins that likewise originated from whole-genome duplication. The traces of this history are thus interestingly preserved.
Another paper traced the effects of the vertebrate ohnologs on brain development. Using the pre-vertebrate amphioxus as an out-group for comparison, they find that the ohnologs that date from the whole duplications are more highly associated with brain cell types and their developmental programs than are other gene duplications- either ones dating from the same time as the whole genome duplications, or since.
"Compared to their closest invertebrate relatives—tunicates and amphioxus—vertebrate brains are highly regionalized and complex."
"Ohnologues were enriched in development, cell-fate commitment, signaling and neurotransmitter transport. By contrast, SSD [small-scale duplication] paralogues were enriched for immune response and sensory perception in all species, a result that matched previous reports."
Lastly, a paper focusing on intermediate genomes, part of a plethora of genome sequencing that has happened since the original analysis, reveals exactly what happened at this time, about 500 million years ago. From a molecular perspective, hagfish are in the same group as lampreys- both parasitic eels that lack real jaws but arise from the vertebrate lineage. They are cyclostomes, while we are gnathostomes. After the first whole genome duplication about 530 million years ago in the common stem lineage, the gnathostomes and the cyclostomes split and each experienced their own, separate genome duplications roughly 490 million years ago. This can be concluded from the differing gene collections that survived from each respective duplication, and their sequences relative to the cyclostome/gnathostome split. Indeed, lampreys and hagfish have six hox clusters instead of four, indicating that a triplication event happened, instead of duplication event, between their split from gnathostomes and the split between lamprey and hagfish.
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| A phylogenetic tree with dates, locating the genome duplications deep in the vertebrate stem lineages. 1R is the first genome duplications, common to all vertebrates. 2R is the duplication in the lineage leading to jawed vertebrates, while CR is the apparent triplication that happened in the lineage leading to cyclostomes. Apologies for the antiquated human being. |
All this genome renovation didn't benefit cyclostomes the way it did gnathostomes, however. Only one group went on to globe-straddling glory, indicating that while genome duplications may be helpful for evolutionary / developmental innovation, they certainly aren't determinative. They are grist for an evolutionary process that remains largely shrouded in mystery- the context and environments of the time, the competitive biosphere, and the internal molecular environment. There is no reason to think that all this is unaccountable by natural processes, but that doesn't mean we have the information to reconstruct it in detail. We should thus be deeply grateful that the scientific community can dig up even this much of our history.
- But how can we take more money away from workers?
- The smearing of Anthony Fauci. And of basic reason.
- Reward and addiction.
- Still stupid ... the Discovery Institute and "information".
