Chromosomes carry the genetic code that determines the characteristics of a living thing. They are fascinating due to the varied factors they determine, the sometimes negative effects they can have and their complexity. Equally interesting are the stories of their discoveries. This series will explore the history of specific chromosomes and their impact on science.

In humans, mitochondrial DNA (mDNA) is regarded as the smallest chromosome, coding for 37 genes and containing approximately 16,600 base pairs. Taryn Cain continues this series by looking at mitochondria.

Let me take you back a bit. 1.4 million years back, in fact. A small bacterium was ingested by a large single-celled organism and, rather than being digested, the smaller body was instead left to its own devices. As time went on, the bacterium began transferring some of its genetic material over to the larger cell, until eventually it was as if the two had never been independent. The small bacterium involved itself with the inner workings of the cell, while the larger organism took over the world. That small bacterium was a mitochondrion, while the larger body became all multi-cellular life on earth. This evolutionary theory is known as symbiogenesis.

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The human genome library on display at Wellcome Collection.

The Y Chromosome

Chromosomes carry the genetic code that determines the characteristics of a living thing. They are fascinating due to the varied factors they determine, the sometimes negative effects they can have and their complexity. Equally interesting are the stories of their discoveries. This series will explore the history of specific chromosomes and their impact on science.

Humans typically have 23 pairs of chromosomes. One of these is comprised of our sex-determining chromosomes, X and Y. Taryn Cain continues this series by looking at the Y chromosome.

The first mammals were tiny, shrew-like creatures that were still many millions of years away from being awoken by the melodic sound of an iPhone alarm or travelling to work in a huge piece of metal crammed with other mammals. While they carried on with their “simple” lives of eating and evading being eaten themselves, their DNA was also a fairly simple arrangement. All their chromosomes were autosomes and male/female differentiation was managed by genes on various autosomes rather than specific sex chromosomes.

Then a mutation occurred.

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Object of the month: You’re not who you think you are

DNA fingerprinting: artwork

DNA fingerprinting. Neil Leslie/Wellcome Images

In our ‘Identity’ exhibition earlier this year, Wellcome Collection examined the scientific and cultural ways in which individuals establish who they are, and how they assert their differences with other people. Genealogy has always provided a powerful means to mould a sense of personal identity and belonging, and over the past decade, following the Human Genome Project, the study of ancestry has been enriched by the increasing pace and declining costs of DNA sequencing technology. In the wake of television programmes such as ‘Who Do You Think You Are?‘, of course, genealogy has become an ever more popular and accessible hobby.

In our permanent gallery ‘Medicine Now’, you can see a number of commercial DNA ancestry kits bought online by our curator Steve Cross. Steve bought them using nothing but his credit card and was not required to seek professional advice before making his DNA sequence available (Steve explains the process in this video). These tests provide a swab that is returned to the company’s laboratory with a sample of your DNA and is used to construct a genetic family tree based on a comparison between your DNA and sequences from living populations kept on the company’s database. Many of these tests claim they can trace your ancestry to a particular part of the world or society – an enchanting prospect, especially for groups longing, for example, to trace their roots back to a time before the upheaval of the international slave trade.

One DNA test on display uses your mitochondrial DNA sequence – an entirely different set of DNA to your ‘regular’ DNA, residing in your mitochondria, tiny organelles in your cells that provide your body with chemical energy in respiration. Because mitochondria are inherited exclusively down the maternal line, mitochondrial DNA is particularly useful for tracing maternal ancestry. The mitochondrial DNA of all living humans is thought to be descended from a single woman who lived in East Africa around 200,000 years ago, a woman named ‘Eve’ by geneticists. Eve is our matrilineal most recent common ancestor. She was not, as is often thought, the only woman alive at the time (as in the biblical Eve), but it just so happens that this otherwise unremarkable woman produced an unbroken line of female descendants. The test result – accompanied by obligatory certificate – comes with a story that depicts the possible life of one of Eve’s descendants, or Steve’s ancestors. It is a work of complete fiction, yet it is testament to our desire to grasp hold of our past, to take ownership of it and, most importantly, to show that our ancestors were human, just like us (forget the fact it plays out like a Palaeolithic episode of EastEnders).

Quite aside from the cost of such services and the many ethical issues they raise – should we be making our DNA sequences accessible to private companies, and who owns this information? – many ancestry tests are notoriously inconsistent. Since the construction of a genetic family tree depends on the limited number of sequences kept on a company’s database (limited perhaps due to cost or the inaccessibility of present-day societies), since populations migrate over time, and since the genetic variations used to ascertain ancestry can vary from company to company, it is quite possible to be linked to a living population you have little to do with. One personality who has famously fallen foul of the ancestry test is Oprah Winfrey, who was initially thought to have Zulu ancestry, a claim now questioned by geneticists.

Along with cloning and genetic modification, DNA sequencing provides another potent example of the double-edged sword brought by advances in medical science. While they open up new horizons of possibility, at the same time they bring into view new questions, challenges and ethical dilemmas.

Cells, complexity and the meaning of life and death

Three mitochondria surrounded by cytoplasm. Wellcome Images

Three mitochondria surrounded by cytoplasm. Wellcome Images

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When Nick Lane told a Packed Lunch audience that his latest theory on the birth of complex life had been nine months in the making, it seemed a fitting gestation period. Unfortunately he had just half an hour to tell us about it.

Nick is a writer and biochemist at UCL, where he holds the first Provost’s Venture Research Fellowship in the Department of Genetics, Evolution and Environment, and is a founding member of the UCL Consortium for Mitochondrial Research. His research on the role of bioenergetics in the origin and evolution of complex life is fascinating.

Bioenergetics is the study of the energy flow through the body. Our energy comes from the molecules in the food we ingest. This energy is converted as part of respiration by mitochondria, the cellular ‘power plants’, into a molecule called ATP that can transport chemical energy within cells, enabling the chemical reactions that support life.

Nick wants to know exactly how and why mitochondria came to be in complex cells. The first forms of life were prokaryotes – small, simple cells. Eukaryotes, larger cells with mitochondria and other organelles, came after prokaryotes on the evolutionary timeline. It is supposed that eukaryotes evolved from prokaryotes. How, and why? It is generally believed that at some point in history, a large prokaryotic cell, such as a phagocyte, engulfed an ancestral form of a mitochondrion that once existed as a free-living organism. There is much argument and acrimony over how, when and why this happened.

After gaining a PhD in biochemistry, Nick spent ten years ruminating on these questions as a professional writer, during which time he “rove across the world – a wonderful freedom”. He has authored three books: ‘Oxygen: The molecule that made the world‘; ‘Power, Sex, Suicide: Mitochondria and the meaning of life‘; and ‘Life Ascending: The ten great inventions of evolution‘ (which has just been awarded the Royal Society Prize for Science Books 2010). But through his exploration of these topics, he found that “time and time” again his own understanding “fell flat on its face”. It was time to go back to the lab.

Nine months ago Nick started scribbling on the back of an envelope. He was sketching out an idea that related extra energy to extra genes. At the moment of endosymbiosis, when an ancestral mitochondrion partnered with a eukaryotic cell, the genes from the mitochondrion provided the large cell with the “raw material for evolution”. Nick now supposes that the extra energy provided by the mitochondrion enabled the cell to support these extra genes. Whereas prokaryotic cells do not have the energy to carry large amounts of DNA, eukaryotic cells, with their mitochondrial powerhouses, can. This theory will be published in ‘Nature’ after five months of review. Nick says “some people will hate this paper”. Argument and acrimony.

Nick is also interested in the role mitochondria play in disease, and particular disorders related to ageing. Free radicals are an essential byproduct of the respiration process that happens in mitochondria. They ‘leak’ from mitochondria, which can cause damage in the body. Other scientists are researching free radicals as the causes of cancer, Parkinson’s disease, schizophrenia and Alzheimer’s. Nick is looking into how antioxidants and calorie restriction diets might be able to ‘mop-up’ free radicals and reduce the number that leak from mitochondria, thus reducing the damage they do. This work is ongoing. For the moment, it seems that mitochondria hold some of the secrets of both life and death.