Study reveals how gene activity shapes immunity across species

October 24, 2018

By sequencing genes from over a quarter of a million cells across six mammalian species, researchers at the Wellcome Sanger Institute, EMBL's European Bioinformatics Institute and collaborators, have shown how genes in the immune response have varied activity between cells and species.

The study, published today (24 October) in Nature, looked in unprecedented detail at the genes that are activated in a cell's initial response to a pathogen invasion - the innate immune response. They measured the activity of thousands of genes in over 250,000 individual cells using single cell genomics technology to chart the evolution of antiviral and antibacterial immunity.

Previous work has shown that many genes in the innate immune response have rapidly evolved in vertebrates. This is thought to be caused by the relentless pressure of attack from pathogens like bacteria and viruses. These include genes that make cytokine and chemokine molecules, which act in a variety of ways - some are inflammatory molecules that alert the body to danger; others restrict a pathogen's ability to multiply and others induce cell death. They represent a successful host strategy to counteract rapidly evolving pathogens.

The team showed that these genes which have evolved rapidly across species, also have highly variable activity in different cells within an individual's tissue.

In contrast, they found that genes which are conserved between species, and regulate the immune response, are more consistently activated across cells within a tissue. These genes may be under tighter constraints because they are involved in many different functions within cells. But, they are also targeted by viruses. These constrained genes represent an Achilles' heel, used by pathogens to subvert the immune system.

Dr Tzachi Hagai, lead author of the research at the Wellcome Sanger Institute said: "We think that this pattern of activation - where some genes are under tight control, and others have more variable activity - has evolved as a way to fine-tune the immune response. It is effective, but balanced. Genes can evolve to help a cell control an attacker, and the use of those genes can vary between cells, so surrounding tissues are not affected by a massive fall-out."

Dr Sarah Teichmann, Head of Cellular Genetics at the Wellcome Sanger Institute and senior author of the research said: "The power of DNA sequencing at the resolution of single cells means this kind of study is now possible. There are an estimated 37 trillion cells in the human body, each with the same genetic code. But individual cells behave differently, they use that genetic code in a different way. By studying individual cells we can understand these fundamental building blocks of life and how they work together - including how they resist pathogens."
-end-
Notes to editors:

Selected websites:

European Bioinformatics Institute (EMBL-EBI)

The European Bioinformatics Institute (EMBL-EBI) is a global leader in the storage, analysis and dissemination of large biological datasets. We help scientists realise the potential of 'big data' by enhancing their ability to exploit complex information to make discoveries that benefit humankind.

We are at the forefront of computational biology research, with work spanning sequence analysis methods, multi-dimensional statistical analysis and data-driven biological discovery, from plant biology to mammalian development and disease.

We are part of EMBL and are located on the Wellcome Genome Campus, one of the world's largest concentrations of scientific and technical expertise in genomics. http://www.ebi.ac.uk

The Wellcome Sanger Institute

The Wellcome Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. To celebrate its 25th year in 2018, the Institute is sequencing 25 new genomes of species in the UK. Find out more at http://www.sanger.ac.uk or follow @sangerinstitute

Wellcome

Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.wellcome.ac.uk

Wellcome Trust Sanger Institute

Related Evolution Articles from Brightsurf:

Seeing evolution happening before your eyes
Researchers from the European Molecular Biology Laboratory in Heidelberg established an automated pipeline to create mutations in genomic enhancers that let them watch evolution unfold before their eyes.

A timeline on the evolution of reptiles
A statistical analysis of that vast database is helping scientists better understand the evolution of these cold-blooded vertebrates by contradicting a widely held theory that major transitions in evolution always happened in big, quick (geologically speaking) bursts, triggered by major environmental shifts.

Looking at evolution's genealogy from home
Evolution leaves its traces in particular in genomes. A team headed by Dr.

How boundaries become bridges in evolution
The mechanisms that make organisms locally fit and those responsible for change are distinct and occur sequentially in evolution.

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Paleontology: Experiments in evolution
A new find from Patagonia sheds light on the evolution of large predatory dinosaurs.

A window into evolution
The C4 cycle supercharges photosynthesis and evolved independently more than 62 times.

Is evolution predictable?
An international team of scientists working with Heliconius butterflies at the Smithsonian Tropical Research Institute (STRI) in Panama was faced with a mystery: how do pairs of unrelated butterflies from Peru to Costa Rica evolve nearly the same wing-color patterns over and over again?

Predicting evolution
A new method of 're-barcoding' DNA allows scientists to track rapid evolution in yeast.

Insect evolution: Insect evolution
Scientists at Ludwig-Maximilians-Universitaet (LMU) in Munich have shown that the incidence of midge and fly larvae in amber is far higher than previously thought.

Read More: Evolution News and Evolution Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.