Harmful mutations and range expansion: computers got it right

Organisms that are expanding their spatial range suffer from a drastic decrease of fitness over time due to the accumulation of harmful mutations. A study led by a team of scientists from the SIB Swiss Institute of Bioinformatics and the University of Bern now provides the first experimental evidence of this theory. The article is published in Genetics and selected in the issue’s highlights.

A ‘built-in’ genetic brake when colonizing new areas
Provided environmental conditions remain unchanged, is there an intrinsic limitation to a species’ spatial expansion? Over the last few years, theoretical work conducted by SIB’s Laurent Excoffiers’ group has been addressing this very question.
Using computer simulations and human DNA datasets, the group showed that species expanding their range were indeed accumulating deleterious mutations on the wave front. And that this negatively affected the species’ fitness.
The reason proposed for this is that natural selection is not very effective at purging harmful mutations in small populations. As a pioneering front is less densely populated, such harmful mutations can reach high frequencies.

From in silico to in vitro experiments
Lars Bosshard, a PhD student at Excoffiers’s lab, was the first author of a study which is now providing the first experimental demonstration of this process.
Using the fast-replicating bacteria Escherichia coli (which is normally found in the guts of warm-blooded animals), he and his colleagues managed to observe the theory at work, by speeding up evolution.
They let E. coli colonize agar plates for 1,650 generations and compared the fitness (ability to grow, speed of spread, etc.) of bacteria from the reference strain to that of bacteria situated at the edge of the pioneer front.
“Bacterial populations are generally considered to be able to adapt to almost any environmental conditions, and their fitness is expected to increase over time in constant environments”, says Lars. “However, despite huge overall population densities, most colonizing bacteria have not been able to purge all their mutation load in our experiment. As a consequence, their fitness was also drastically reduced.”

From bacteria expansion to tissue growth
The findings are also shedding light on the mutation accumulation process occurring in other organisms, such as humans and plants, and other types of expansions.
“During their development, multicellular organisms go through billions of cell divisions, each time accumulating somatic mutations. Deleterious somatic mutations, which are intimately related to cancer, may thus spread during tissue growth and contribute to other diseases”, concludes Lars. He adds, “Our results therefore have potential implications for predicting the genetic changes occurring during the growth of solid tissues in eukaryotes”.

Bosshard L et al. Accumulation of deleterious mutations during bacterial range expansions. Genetics, October 1, 2017 vol. 207 no. 2 669-684, https://doi.org/10.1534/genetics.117.300144

Read about the group’s previous work on mutation accumulation during early human migrations

expanding colony v2

Escherichia coli growing on an agar plate. The bacteria, expressing the green fluorescent protein (GFP), was observed for two hours with a confocal microscope.