Quadrupling of genes over 550 million years behind vertebrate evolution

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London, June 19 : Sequencing the genome of a marine invertebrate known as the lancelet, University of California-Berkeley scientists have come up with an explanation as to how a four-fold duplication of the genes took place during vertebrate evolution over the past 550 million years.

Late geneticist Susumu Ohno once described gene duplication as the most important force in the evolution of higher organisms, and based on his theory, it was reckoned that the human genome must contain up to 100,000 distinct genes.

When the Human Genome Project came to light, it was estimated that humans these days have only 20,000 to 25,000 genes.

It was an indication that, if the primitive genome of the ancestors doubled and redoubled, most of the duplicate copies of genes must have lost.

The UC-Berkeley research team insist that their latest study on the lancelet, or amphioxus, genome shows the same to be the case.

"Amphioxus and humans had a common ancestor 550 million years ago, which allows us to use amphioxus as a surrogate for that ancestor in terms of understanding how vertebrate genomes evolved," Nature magazine quoted Daniel S. Rokhsar, a faculty member in the UC Berkeley's Center for Integrative Genomics, as saying.

"If you compare the 23 chromosomes of humans with the 19 chromosomes of amphioxus, you find that both genomes can be expressed in terms of 17 ancestral pieces. So, we can say with some confidence that 550 million years ago, the common ancestor of amphioxus and humans had 17 chromosomal elements," added Rokhsar, who authored the study with a post-doctoral fellow named Nicholas H. Putnam.

The researchers said that each of the 17 chromosomal elements was duplicated twice in the evolution of vertebrates, and most of the routine "housekeeping" genes lost the extra copies thereafter.

Putnam said that the genes that were left found new functions, which make humans different from all other creatures.

"These few thousand genes have been retooled to make humans more elaborate than their simpler ancestors. They are involved in setting up the body plan of an animal and differentiating different parts of the animal. The hypothesis, pretty strongly supported by this data, is that the multiplication of this particular kind of gene and differentiation into different functions was important in the formation of vertebrates as we know them," he said.

For their study, the researchers collected lancelets from the 15-foot-deep waters of Tampa Bay, Florida, and upon a thorough analysis, they found that the creature's 19 chromosomes map onto the human genome in 17 segments, each of which is represented four times in the human genome.

"The human genome is a mosaic of these 17 ancestral pieces constructed by two rounds of duplication, followed by gene loss and chromosome rearrangments and fusions. That took some computational gymnastics to sort out, but the evidence is still there," said Rokhsar.

A co-author on the study, Linda Z. Holland, who is an expert on the biology and genetics of amphioxus at the Scripps Institution of Oceanography at UC San Diego, said: "The most exciting thing that the amphioxus genome does is provide excellent evidence for the idea that Ono proposed in 1970, that the human genome had undergone two rounds of whole-genome duplication with subsequent losses. We have been kicking that idea around with very little proof for a long time. This genome sequence really clinches that."

Scientists previously thought that the sea squirt Ciona intestinalis (or vase tunicate) belonged to the earliest chordate lineage because of its very simple body plan.

However, comparison of the lancelet, sea squirt, and human genomes suggest that the lancelet lineage diverged before the tunicates and vertebrates.

"Sea squirts and their relatives have taken the basic chordate genome and simplified it in various ways, while amphioxus retains those features in its genome," said Rokhsar.

He revealed that his team was trying to reconstruct the evolution and divergence of a creature similar to lancelet into three types of chordates - cephalocordates like the lancelet, urochordates like the sea squirt, and vertebrates like humans - at the end of the Cambrian period 550 million years ago.


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