From micro to macro: tracing the building blocks of chromosomes

2 November 2021

With help from Australia’s largest research supercomputing facility, scientists have peeked into the chromosome evolution that set us mammals apart from other vertebrates.

For years, researchers have noticed the existence of a type of tiny chromosomes called microchromosomes. They are ubiquitously seen in birds and reptiles but absent in mammals, including humans.

Where are these microchromosomes from, what roles do they play, and why don’t we have them? Questions as such have puzzled researchers for a long time, as microchromosomes were really hard to study.

“They are barely visible under the microscope and very challenging to obtain the DNA sequence data,” said Dr Hardip Patel at the John Curtin School of Medical Research.

Central bearded dragon cells under a microscope, showing the tiny microchromosomes huddled together amongst the larger chromosomes. Image: Shayer Alam

Thankfully, advanced DNA sequencing technology has enabled researchers to sequence microchromosomes end-to-end accurately.

Working with researchers across Australia and Europe, Dr Patel set out to understand the evolutionary origins of microchromosomes by performing large scale comparisons.

Still, this is no simple task—the project required 2 million CPU hours to process the data. If all were assigned to one single PC, the work would take 28 years to finish.

“We were fortunate to have critical partnerships with Australia’s National Computational Infrastructure to undertake this project,” said Dr Patel.

The team lined up genome sequences of seven species of birds, ten reptiles, three mammals, and lancelet, and looked for conservation patterns.

“It was astonishing to see how well these tiny microchromosomes are conserved between birds and reptiles that shared common ancestor about 300 million years ago,” said Dr Patel.

More surprisingly, these microchromosomes were similar even to those of a lancelet, a fish-like invertebrate that diverged from the vertebrate lineage 684 million years ago.

On the contrary, mammals appear to have undergone frequent fusions between microchromosomes to form macrochromosomes.

While some vestiges of fused microchromosomes have been preserved in egg-laying mammals such as platypus, others have faded in a series of subsequent reshuffling.

These findings, published today in PNAS, suggest that microchromosomes were the ancestral state of vertebrates. Although invisible in extant mammals, they served as the building block of chromosomes in us as they did in birds and reptiles.

The authors think these results highlight the need to rethink our place as mammals within an evolutionary context.

“The new knowledge helps explain why there is such a large range of mammals with vastly different genomes inhabiting every corner of our planet,” said Professor Jennifer Graves at La Trobe University, the senior author of the PNAS paper.

“The tree of life offers unique examples of chromosome structures that affect how the genome functions and evolves in response to its environment,” remarked Dr Patel, “Studying diverse groups of animals provides unique opportunities to understand the complex biology of human health and disease.”