Ancient blood lines: tracing the evolution of haemoglobin

Most of the biological processes that keep us alive depend on multiple proteins working together. One of biology’s great puzzles is how this multitude of proteins and their complex interactions came to be.

Now, an international team, including University of Oxford Professor Justin Benesch and DPhil student Shane Chandler from the Department of Chemistry, has revealed that complexity can evolve through surprisingly simple mechanisms. They identified the evolutionary “missing link” through which haemoglobin — the protein complex that transports oxygen in our blood — evolved from simple precursors.

They found that the emergence of modern haemoglobin’s structure and function was triggered by just two mutations more than 400 million years ago. The team, led by the University of Chicago, also included researchers from Texas A&M University and University of Nebraska-Lincoln. 

The study, Origin of complexity in haemoglobin evolution, was published today in the journal Nature. 

The team’s strategy was a kind of molecular time travel going back hundreds of millions of years. They used statistical and biochemical methods to reconstruct and characterise ancient proteins before, during and after the earliest forms of haemoglobin were evolving. This allowed them to identify the missing link during haemoglobin evolution – a two-part complex, which existed before the last common ancestor of humans and sharks. This ancient complex did not yet possess any of the critical properties that allow modern haemoglobin to carry oxygen from the lungs to the brain, muscles and other tissues. 

A key question was to determine through which interfaces the ancient proteins assembled, a question tackled by Chandler and Benesch in Oxford, who said: 'Part of the puzzle that needed to be solved was how haemoglobin attained its four-subunit structure. This required us to develop new methods for detecting protein-protein interfaces and revealed the historical order of assembly of this remarkable molecule.'

The traditional view of how biological complexity evolves is that it increases gradually over the course of many mutations that each cause small improvements in fitness. The new research shows that complicated new structures can come into being very quickly.

University of Chicago Professor, Joseph Thornton, who led the study, said: 'We were blown away when we saw that such a simple mechanism could confer such complex properties. This suggests that jumps in complexity can happen suddenly and even by chance during evolution, producing new molecular entities that eventually become essential to our biology.'

Read the study, “Origin of complexity in haemoglobin evolution,” in the journal Nature.