Rockefeller University New York, NY
Notions of self: genes and agendas.
Genes are chemical blueprints made of DNA (deoxyribose nucleic acids) that instruct a cell how to make proteins. Proteins are the chief effector molecules of life – those molecules that facilitate the essential chemistry of life, termed biochemistry. Thus, genes critically define which proteins need to be present in each of the approximately thirty-seven trillion cells of the human body for it to be healthy and alive.
However, compared to the total amount of DNA in a cell (called the genome), only a relatively small proportion of DNA (~1-2%) comprises genes. In contrast, an enormous amount of our DNA has resulted from the proliferation of DNA sequences referred to as transposons (~40%). Transposons are called such because these DNA sequences have the ability to move (or transpose) from one location to another within the genome. A particular class of these transposons has been able to multiply within the human genome to an enormous extent because it employs a ‘copy and paste’ mechanism: the original sequence is maintained, and a new copy of that sequence is created and inserted elsewhere in the genome. Over our evolutionary history, these sequences have accumulated in vast numbers, littering our genome. We will focus on this class of transposon, known as retrotransposons.
These elements do not appear to meaningfully contribute to the maintenance of our health but have clearly been shown to contribute to cancer and disease. To counter this threat, our genes have evolved in ways that attempt to exert control over the expansion of transposons. It can therefore be said that each living cell and the genes that contribute to the maintenance of life are locked in an arms race with selfish elements whose only function appears to be expansion within the genome at any cost. This struggle has persisted throughout our entire evolutionary history (> 600 million years), from single cells to human beings, illustrating the degree to which even at our most fundamental molecular level, life is an unending succession of struggles, victories, and defeats. We are the stage of a living drama, an internal struggle: genes and their agendas.