Reconstructing part of the genome of a common mammalian ancestor 30/11/04. By the Howard Hughes Medical Institute Researchers have re-created part of the genome of the common ancestor of all placental mammals, a small shrew-like creature that prowled the forests of what is now Asia more than 80 million years ago.

By comparing DNA sequences of 19 species of existing mammals, including humans, the researchers have reconstructed a large segment of DNA in the species from which all of today's placental mammals arose. They estimate that the reconstruction is 98 percent accurate.

The project, led by David Haussler, a Howard Hughes Medical Institute investigator at the University of California, Santa Cruz, based their reconstruction efforts around a region of the genome that covers about 1.1 million bases flanking the cystic fibrosis transmembrane conductance regulator (CFTR) gene. That region of the genome has been sequenced in a large number of species.

Feature: Cystic fibrosis

Efforts to extract DNA from fossils generally have been disappointing because DNA molecules break down over time. Geneticists therefore have turned to a technique that has been called '[computerised] paleogenomics' to infer the DNA sequences of past organisms.

All of the placental mammals living today are descended from an early species that lived tens of millions of years before the final demise of the dinosaurs. This species underwent a rapid diversification, splitting into the evolutionary lineages that have led to today's placental mammals. Because all of these species are descended from a common ancestral species, they all have inherited specific DNA sequences from that ancestor.

Reconstructing the DNA sequence of this ancestor is comparable to drawing conclusions about the first automobile by observing the many different kinds of automobiles existing today. Though the separate makes of automobile have changed and diversified over time, they share features that were present in their conceptual ancestor: four rubber tires, a windshield, and an internal combustion engine, for example.

The challenge for Haussler and his colleagues was to determine how the DNA sequence of the common ancestor changed in each of the evolutionary lineages leading to current mammals. This task is not so complicated where individual nucleotides changed in a particular lineage, because the original nucleotide often was retained in other lineages. It is much more difficult where stretches of DNA were inserted or deleted in the genomes of particular species.

"DNA comes and goes," said Haussler. "Some DNA gets deleted, and new DNA gets inserted. Tracking the history of these insertions and deletions is essential."

Haussler's research team built a computer program that looked both for individual nucleotide changes and for insertions and deletions in the DNA sequences of a number of mammalian species, including species of pig, horse, cat, dog, bat, mouse, rabbit, gorilla, chimpanzee and human.

Knowing about the genome of the common ancestor of placental mammals creates tremendous scientific opportunities, according to Haussler. Most important, it reveals how DNA sequences have changed in each of the lineages leading to one of today's mammalian species.

For example, studies of the FOXP2 region of the genome indicate that changes in FOXP2 may have contributed to the evolution of fluent speech in the human lineage. "The nucleotide is C for more than 300 million years, and then suddenly it's A, just in the human lineage," said Haussler. "You can see it. That's the excitement of documenting these dramatic events that can change the nature of an organism over evolutionary time."

Feature: The FOXP2 story

Haussler said he is confident that significant medical benefits will accrue from a better understanding of the genome, although this particular project was motivated by pure scientific curiosity. "I want to know in molecular detail how we evolved from a furry, nocturnal, shrew-like creature, and now is the time to find out."

Adapted from a press release by the Howard Hughes Medical Institute .

Further reading

Blanchette M, Green ED, Miller W, Haussler D (2004) Reconstructing large regions of an ancestral mammalian genome in silico. Genome Res 14:2412-23. Abstract . Full text