08 August 2016
Emeritus Professor of Paediatric Genetics, Institute of Child Health, University College LondonAppeared in BioNews 863
Over the last two decades developments in genetics, and more recently in the science of epigenetics, have caught the public's imagination. Hardly a day goes by without some media reference to a particular feature 'being in the DNA'. This phrase is no longer confined to genetically determined characteristics, but can extend to the cultural aspects of entire nations – 'Opera is in the Italian DNA' (The Observer); 'Carols are part of our cultural DNA' (Radio 4, Today). It seems that we're thinking not just of nurture and nature, but of 'second nature' too – those deeply embedded, almost instinctive behaviours. 'In the DNA' is now used as a catch-all phase for what makes you who you are – the biologically embedded determinants of one's development.
This language is countered to some extent by phrases like 'Why your DNA isn't your destiny' (Time magazine). This blurring of Nature (inherited DNA code) and Nurture (environment) is compounded by evidence that some induced epigenetic alterations can be transmitted to future generations. This is the mechanism by which environmental cues during early development and beyond can result in enduring changes to our gene activity. Although not changing the DNA code itself, these induced changes can last a lifetime and influence our health and well-being.
Does this blurring of boundaries matter? I believe it can when one moves to specifics. One such example is conception by gamete donation. Last November, following a misleading newspaper headline that claimed 'Infertile mums "pass on DNA"', Dr Jess Buxton wrote a comment piece for BioNews in which she explained that the truth is that research published last year indicates that infertile mums can pass on RNA – not DNA (see BioNews 826). They are not passing on genes – those come from the egg donor.
There are good reasons to guard against such factual errors, if only because of the human tendency to 'pick and mix' information to build stories about the things that mean most to them. Fertility professionals should think twice about going along with the understandable desire of some donor-gamete recipients to downplay the fact that all their baby's genes come with the egg and sperm. They should by all means discuss the role the carrying mother plays in their baby's development, but they should not encourage a disregard for the donor's genes. Indeed, an important element of gamete-donor selection is to consider potential genetic risks to future children. The candidate donor's family history is assessed to exclude a high risk of transmitting a serious, inherited disease, and a DNA sample is screened for 'hidden' risks, such as common recessive mutations (e.g. carrier status for cystic fibrosis). Nevertheless, the research suggests that, even before implantation, a donor-recipient mother – like any mother – may be sending molecular signals to the embryo that can directly influence its gene activity. Scientists are exploring the molecular details at the boundary between generations, and the link between genetic inheritance and the nurturing womb.
As Dr Buxton explained, the RNA molecules that were passed to the pre-implantation embryo were microRNAs: 'As the name suggests, microRNAs are short sections of RNA, a chemical relative of DNA. Their job is to fine-tune the activity levels of genes during development and throughout life. As such, they are a key part of the epigenetic machinery. MicroRNAs, like proteins, are themselves the products of genes – there are over 2500 known human microRNA genes. Each microRNA is predicted to have hundreds to thousands of different target genes, enabling them to influence complex networks of gene activity in processes ranging from growth and development to immunity.' The study focused on a particular microRNA called hsa-miR-30d, which was packaged into a tiny vesicle called an exosome. This is how microRNAs are often transported around the body – or in this case between the lining of the mother's womb and her 'receptive' pre-implantation embryo.
In an egg-donor situation, the DNA of the carrying mother could dictate the formation of a microRNA that enters the embryo to influence the activity of some of its own genes, probably those involved in the implantation process. Here is a tentative description of one of the first molecular investments a recipient mother can make in her embryo. As such, some recipient mothers may find this information comforting. But, generally, recent discoveries in epigenetic regulation across the generations (e.g. in relation to smoking and diet) bring added responsibilities – not only for the baby they are carrying but for potential grandchildren – for the father as well as the mother. Research in mice supports the notion that some of the microRNAs associated with a man's lifestyle are loaded into mature sperm and influence the early development of the next generation.
Greater public recognition of these transgenerational responses to parental experience may well have contributed to the blurring of the boundaries implicit in phrases such as 'in our cultural DNA'. In the past, the word DNA was synonymous with genes and genetic inheritance but it has now come to embrace cultural continuity as well. This is going well beyond the science. One thing we can say is that we cannot choose our parents and ancestors. Beyond families at specific genetic risk, there is not much any of us can do about the genes we are dealt, but we can invest in the future.