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Surveying the Genomic Landscape of Modern Mammals

A rhesus macaque and a Tasmanian devil.
A rhesus macaque and a Tasmanian devil.

A study published today in Cell  compares regulatory DNA sequences among 20 species of modern mammals, showcasing how mammalian genomes have found new uses for ancient genes.

The evolution of mammals has been ongoing for about 180 million years, with a burst of numbers and diversity about 66 million years ago. Then, an asteroid impact led to mass extinctions, and the small, scurrying, hairy ones found vacated real estate.


Fossils help in studying past life, but even more useful is to compare DNA sequences among modern species. The more of a gene or genome sequence a pair of species shares, the more recently they shared an ancestor. That is a more likely explanation for similarity at the DNA level, I think, than that two species ended up with nearly identical sequences by chance. And if researchers know the mutation rate for a specific gene, then they can assign approximate time frames to species’ divergence.

Diego Villar, from the University of Cambridge Cancer Research UK, Paul Flicek, head of Vertebrate Genomics at the European Molecular Biology Lab EMBL-EBI, and their colleagues identified promoter and enhancer regions in DNA from liver cells from the selected 20 species of placental mammals.

Promoters are short sequences at the starts of genes that control their transcription into RNA, from which protein is translated. Enhancers are short DNA sequences, typically located a bit away from the genes that they control, that bring different genes together as the chromosome unwinds and loops about itself. So both promoters and enhancers control gene expression, one from near, one from afar.

Tree shrew (wikispecies)
Tree shrew (wikispecies)

The list of participating mammals in the study is diverse, but heavy on primates, rodents, and sea dwellers: human, macaque, vervet and marmoset (primates); mouse, rat, naked mole rat and guinea pig (rodents); dolphin and two whales (cetaceans); and rabbit, tree shrew, pig, ferret, dog, cow, cat, opossum, and Tasmanian devil.

The researchers discovered that promoters tend to have evolved recently – which means over the past 40 million years. In contrast, most enhancers are derived from sequences that have been around for more than 100 million years, but have been co-opted to take on new functions. So species and their genomes can retain what’s worked in the past via natural selection, but can also tap into ancient sequences for new uses.

I’d use the word “repurpose” to describe enhancers’ links to past DNA, but “purpose” is a banned word in evolutionary biology, because it implies intent, which implies a creator. The researchers use the slightly less teleological “redeployment of ancestral DNA.” This approach is different from the gene duplication route to microevolutionary change I learned in graduate school. In that model a gene doubles, perhaps by a slip during DNA replication at a short repeated sequence, and then one copy, through mutation, acquires a novel function that persists if it does no harm.

An evolutionary success
An evolutionary success

It’s reassuring that a genome has more than one way to change, because that’s what evolution is: change. It is not directional, not leading towards someone’s concept of perfection, and we are certainly no more highly evolved, whatever that means, than a bacterium or cockroach. They’ve been around a lot longer than we have.

In 1982, Stephen Jay Gould and Elizabeth Vrba coined the term  exaptation to distinguish novel use of old information from natural selection, which instead results in an adaptation (a trait that makes it more likely to leave fertile offspring.) Exaptation is a little like what my daughter Heather says whenever I want to buy new furniture. “Use something already in the house.

My husband Larry demonstrating his exaptation of kitchen tools to capture rodents. He is a retired chemist with nearly 100 patents.
My husband Larry has exapted kitchen tools to capture rodents. He is a retired chemist with nearly 100 patents.

Some popular explanations of biological diversity do not take advantage of the endless information to be mined from DNA sequences. Consider the appearance of everything living within the span of a week, plunked down on the lovely Earth by a supernatural force.

According to Genesis, on day 5, God said, “Let the water teem with living creatures, and let birds fly above the earth across the vault of the sky.” Day 5 would seemingly cover the dolphin and pair of whales featured in the Cell paper, but the biblical description is classification by habitat, so includes fish and birds too.

bibleLet the land produce living creatures according to their kinds: the livestock, the creatures that move along the ground, and the wild animals, each according to its kind,” sayeth God on day 6. Towards the end of that great day, we humans came along to lord over everyone else, a situation evidenced by the terms “livestock” and “wild,” a somewhat more subjective taxonomy than comparing DNA sequences and mutation rates. Presumably this day would include the other species in the Cell paper not yet specifically mentioned.

Another skewed view of evolution is the common line-up of creatures, with humans coming after chimps as the most “advanced” species. Cartoonists sometimes put stooped-over office workers in the final slot, or someone hunched over a cell phone. These alignments are offshoots of the “Great Chain of Being,” a religious ordering of everything in the universe.

HaeckelBut evolution tends to be branching, not linear. We share an ancestor with chimps, from around 6 to 7 million years ago, but we didn’t morph directly from them. Even when a lineage appears to be linear, likely offshoots died out along the way, perhaps leaving a bit of themselves lurking in modern genomes, like the Neanderthals.

So now I’ve angered the anti-GMO folk in last week’s post, and the intelligent design crowd in this week’s post. Perhaps I should take next week off.

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