Birth of a species

This article is part of our series, “Evolution in action”. To view the entire collection, click here. 

When Charles Darwin visited the Galápagos Islands in the early 1830s, he noticed finches with similar appearances but distinct beak shapes. Only when he returned to London did the realization struck him: They were not a single but different, closely related species of finches. This observation would go on to profoundly shape his ideas on evolution, particularly the kind in which a common ancestor gives rise to different species with unique characteristics.

Today, the finches' adaptation to their varied ecological conditions is understood as a classic tale of divergent evolution — picture it as a single tree trunk representing a common ancestral species. With time, the trunk begins to split into branches, each representing a unique evolutionary path.

Whitehead Institute researchers are keenly tracing the path of such changes.  By studying the life cycle of everything from an individual cell to complex organisms, they hope to learn more about how — and why — genes mutate over time and its implications for health and disease.

Cancer’s origin story

Often the moments that matter in cancer — mutation, proliferation, metastasis — are fleeting, but the lab of Whitehead Institute Member Jonathan Weissman has pioneered a novel lineage tracing approach that offers them unprecedented resolution to study each event in a cancer’s origin story. The researchers use CRISPR technology to embed cells with an inheritable DNA barcode. As cells divide, the barcodes undergo slight modifications, allowing the researchers to then reconstruct a detailed family tree of individual cells, just like an evolutionary tree of related species.

In a recent project in collaboration with Tyler Jacks, the Daniel K. Ludwig Scholar and David H. Koch Professor of Biology at the Massachusetts Institute of Technology (MIT), and computer scientist Nir Yosef, associate professor at the University of California Berkeley and the Weizmann Institute of Science, researchers used this technology to track lung cancer cells from the very first activation of cancer-causing mutations.

With this approach, they found that cells within the same tumor embarked on unique evolutionary paths depending on their gene expression — certain subpopulations were better at growth and survival and, over time, entered cell states that have been linked to metastasis.

In another project, the Weismann lab zoomed in on small genetic differences between human stem cells and chimp stem cells, uncovering a group of genes essential to chimps, but not to humans, that help control the cell cycle, which regulates when and how cells decide to divide. The researchers hope findings from these projects will ultimately enable them to narrow down differences in genes that are involved in disease.

The fruit fly family tree

Whitehead Institute Member Yukiko Yamashita is looking at another key aspect of divergent evolution, known as speciation. This is the formation of new species from existing ones that are not reproductively compatible together. When members of a species are isolated from each other, populations within the species evolve in unique ways. Over time, genetic differences accumulate between them, leading to this inability to interbreed and produce viable offspring.

The work of Yamashita and former postdoctoral fellow Madhav Jagannathan, currently an assistant professor at ETH Zurich, Switzerland, illuminates biological underpinnings of reproductive incompatibility in two related fly species. 

Yamashita and Jagannathan found that a type of repetitive DNA — satellite DNA — that has previously been thought of as “junk” plays a key role in speciation. It keeps cells’ chromosomes together in a single nucleus through the help of proteins that specifically bind to it.

When the researchers removed one of these proteins in the fruit fly Drosophila melanogaster, some chromosomes ended up in a separate, small nucleus, which was often lethal to the flies. Soon, the researchers were able to connect the dots: if this piece of satellite DNA is essential for survival but its sequence is different between species, it could be one reason why two related species are reproductively incompatible.

This discovery proved how small changes at a molecular level can have big implications for growth and survival of an organism.

More than dead weight

Just like satellite DNA, there are other molecules with roles that aren’t fully understood. Some of these molecules are small, noncoding RNAs, called microRNAs, that can regulate gene expression. Regulating gene expression and consequently protein production, is a powerful way to impact which traits appear. The work of Whitehead Institute Member David Bartel has shown that microRNAs regulate the expression of most human genes.

MicroRNAs function by binding to specific messenger RNA (mRNA) molecules within the cell’s cytoplasm. These messenger RNAs carry instructions, read or “transcribed” from DNA, for generating new proteins. When the two bind, microRNAs can trigger the degradation of mRNA molecules or prevent the translation of instructions into functional proteins. Through these mechanisms, microRNAs act as sculptures of the transcriptome to tune protein production and thereby regulate gene expression.

Now, tens of thousands of scientists around the world use a tool created by the Bartel lab, called TargetScan, to predict how strongly a microRNA will bind to different mRNAs and repress gene expression. 

Oxygen for life

Beyond plants and animals, the evolution of bacteria has had a tremendous impact on life on Earth. Whitehead Fellow Lindsey Backman is interested in understanding how anaerobic bacteria on our skin, in oral cavities, and in the human gut adapt to an ever-changing environment.

“The human microbiome is made up of bacteria that first emerged in the oxygen-free world,” says Backman. These bacteria used a group of proteins called glycyl radical enzymes to help them metabolize nutrients and turn them into cellular energy. These enzymes worked just fine for millions of years, until oxygen filled the Earth’s atmosphere and oceans.

Since glycyl radicals are easily damaged by oxygen, some bacteria developed a new mechanism for still processing nutrients with these efficient enzymes. Backman calls this the spare part protein.

“Think of this as a tire that has gone flat,” she says. “Instead of replacing the car, you change the tire to restore function.”

These unique metabolic pathways that allow bacteria to defend themselves from oxidative stress and proliferate contain important clues for fighting antibiotic resistance and for understanding and treating complex human diseases.

In each of these cases, Whitehead Institute researchers have found that change, at a genetic level, profoundly affects a cell or an organism’s chances of survival and reproduction, and also has important implications for our understanding of  health and disease.  To learn more about divergent evolution, read our cartoon explainer.