Nav: Home

First mutations in human life discovered

March 22, 2017

The earliest mutations of human life have been observed by researchers at the Wellcome Trust Sanger Institute and their collaborators. Analysing genomes from adult cells, the scientists could look back in time to reveal how each embryo developed.

Published in Nature today, the study shows that from the two-cell stage of the human embryo, one of these cells becomes more dominant than the other and leads to a higher proportion of the adult body.

A longstanding question for researchers has been what happens in the very early human development as this has proved impossible to study directly. Now, researchers have analysed the whole genome sequences of blood samples (collected from 279 individuals with breast cancer) and discovered 163 mutations that occurred very early in the embryonic development of those people.

Once identified, the researchers used mutations from the first, second and third divisions of the fertilised egg to calculate which proportion of adult cells resulted from each of the first two cells in the embryo. They found that these first two cells contribute differently to the whole body. One cell gives rise to about 70 percent of the adult body tissues, whereas the other cell has a more minor contribution, leading to about 30 percent of the tissues. This skewed contribution continues for some cells in the second and third generation too.

Originally pinpointed in normal blood cells from cancer patients, the researchers then looked for these mutations in cancer samples that had been surgically removed from the patients during treatment. Unlike normal tissues composed of multiple somatic cell clones, a cancer develops from one mutant cell. Therefore, each proposed embryonic mutation should either be present in all of the cancer cells in a tumour, or none of them. This proved to be the case, and by using these cancer samples, the researchers were able to validate that the mutations had originated during early development.

Dr Young Seok Ju, first author from the Wellcome Trust Sanger Institute and the Korea Advanced Institute of Science and Technology (KAIST), said: "This is the first time that anyone has seen where mutations arise in the very early human development. It is like finding a needle in a haystack. There are just a handful of these mutations, compared with millions of inherited genetic variations, and finding them allowed us to track what happened during embryogenesis."

Dr Inigo Martincorena, from the Sanger Institute, said: "Having identified the mutations, we were able to use statistical analysis to better understand cell dynamics during embryo development. We determined the relative contribution of the first embryonic cells to the adult blood cell pool and found one dominant cell - that led to 70 percent of the blood cells - and one minor cell. We also sequenced normal lymph and breast cells, and the results suggested that the dominant cell also contributes to these other tissues at a similar level. This opens an unprecedented window into the earliest stages of human development."

During this study, the researchers were also able to measure the rate of mutation in early human development for the first time, up to three generations of cell division. Previous researchers had estimated one mutation per cell division, but this study measured three mutations for each cell doubling, in every daughter cell.

Mutations during the development of the embryo occur by two processes - known as mutational signatures 1 and 5. These mutations are fairly randomly distributed through the genome, and the vast majority of them will not affect the developing embryo. However, a mutation that occurs in an important gene can lead to disease such as developmental disorders.

Prof Sir Mike Stratton, lead author on the paper and Director of the Sanger Institute, said: "This is a significant step forward in widening the range of biological insights that can be extracted using genome sequences and mutations. Essentially, the mutations are archaeological traces of embryonic development left in our adult tissues, so if we can find and interpret them, we can understand human embryology better. This is just one early insight into human development, with hopefully many more to come in the future."
-end-
Selected websites:

Korea Advanced Institute of Science and Technology (KAIST)


KAIST was established by the Korean government in 1971 as a research university to grant graduate degrees only in science and technology. In 1986, the university broadened its mission to offer undergraduate programs. Over the past 45 years, KAIST has played a critical role in Korea's rapid economic growth, conducting the majority of the nation's strategic research and development (R&D) projects and training highly skilled researchers and engineers. Today, KAIST has received international recognition as a global research university, appearing annually since 2008 in the top 100 world universities. http://www.kaist.edu

The Wellcome Trust Sanger Institute

The Wellcome Trust 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. http://www.sanger.ac.uk

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 Cell Division Articles:

Scientists detail how chromosomes reorganize after cell division
Researchers have discovered key mechanisms and structural details of a fundamental biological process--how a cell nucleus and its chromosomal material reorganizes itself after cell division.
Targeting cell division in pancreatic cancer
Study provides new evidence of synergistic effects of drugs that inhibit cell division and support for further clinical trials.
Scientists gain new insights into the mechanisms of cell division
Mitosis is the process by which the genetic information encoded on chromosomes is equally distributed to two daughter cells, a fundamental feature of all life on earth.
Cell division at high speed
When two proteins work together, this worsens the prognosis for lung cancer patients: their chances of survival are particularly poor in this case.
Cell biology: The complexity of division by two
Ludwig-Maximilians-Universitaet (LMU) in Munich researchers have identified a novel protein that plays a crucial role in the formation of the mitotic spindle, which is essential for correct segregation of a full set of chromosomes to each daughter cell during cell division.
Better together: Mitochondrial fusion supports cell division
New research from Washington University in St. Louis shows that when cells divide rapidly, their mitochondria are fused together.
Seeing is believing: Monitoring real time changes during cell division
Scientist have cast new light on the behaviour of tiny hair-like structures called cilia found on almost every cell in the body.
Exhaustive analysis reveals cell division's inner timing mechanisms
After exploring every possible correlation, researchers shed new light on a long-standing question about what triggers cell division.
Molecular guardians monitor chromosomes during cell division
One of the worst things that can happen to a cell is to end up with the wrong number of chromosomes.
First interactive model of human cell division
Mitosis -- how one cell divides and becomes two -- is one of the fundamental processes of life.
More Cell Division News and Cell Division Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#543 Give a Nerd a Gift
Yup, you guessed it... it's Science for the People's annual holiday episode that helps you figure out what sciency books and gifts to get that special nerd on your list. Or maybe you're looking to build up your reading list for the holiday break and a geeky Christmas sweater to wear to an upcoming party. Returning are pop-science power-readers John Dupuis and Joanne Manaster to dish on the best science books they read this past year. And Rachelle Saunders and Bethany Brookshire squee in delight over some truly delightful science-themed non-book objects for those whose bookshelves are already full. Since...
Now Playing: Radiolab

An Announcement from Radiolab