Your Genome? Which One?
A new finding about DNA differences in somatic cells overthrows a common assumption and might have dramatic implications for evolutionary studies.
Young's Law (from Murphy's catalog of perverse tendencies in nature) states that all great discoveries are made by mistake. A corollary is that the greater the funding, the longer it takes to make the mistake, but we won't go there. Anyway, a team of Yale scientists wasn't looking to overturn a huge assumption in genetics -- but they did. The ripple effects of their discovery remain to be seen.
We've all been told that every cell in our body has a copy of our unique genetic code. That's one of those simplistic beliefs that sounds sensible but is almost impossible to check. Doesn't the whole body arise from cell divisions of a single zygote with its unique genetic code? Yes, but it doesn't necessarily follow that the genes in cells downstream don't get modified. That was just assumed.
Advances in sequencing technology are now making it possible to check this assumption. Researchers working with induced pluripotent stem cells (iPSC's) have noticed copy number variations (CNV) in cells derived from skin cells. Most assumed these changes occurred in the process of inducing them to the pluripotent state. The Yale team, publishing in Nature, explored how these CNV's arise. In the process, they checked whether CNV's are also found in the somatic cells from which the iPSC's were derived:
Using PCR and digital droplet PCR, we show that at least 50% of those CNVs are present as low-frequency somatic genomic variants in parental fibroblasts (that is, the fibroblasts from which each corresponding human iPSC line is derived), and are manifested in iPSC lines owing to their clonal origin. Hence, reprogramming does not necessarily lead to de novo CNVs in iPSCs, because most of the line-manifested CNVs reflect somatic mosaicism in the human skin.... Overall, we estimate that approximately 30% of the fibroblast cells have somatic CNVs in their genomes, suggesting widespread somatic mosaicism in the human body. Our study paves the way to understanding the fundamental question of the extent to which cells of the human body normally acquire structural alterations in their DNA post-zygotically. (Emphasis added.)"Somatic mosaicism" is jargon for the finding that genomes differ from cell to cell -- not only in copy number variations (CNV's), but in single nucleotide polymorphisms (SNP's). The assumption that you have one genome is thus falsified. You have lots of genomes! Press releases from Yale and Stanford discuss the findings.
In light of the ENCODE project, this makes sense. Gene regulation processes are likely to cause structural rearrangements of genes in particular tissues and organs. Mutagens are also likely to cause changes in some cells and not others.
What will this mean to genetics and evolutionary studies? Ever since the Human Genome Project published its epochal map of "the human genome," researchers have been publishing maps of "the" chimpanzee genome, "the" corn genome, "the" pig genome and many others. The question arises now, do such things even exist in the real world? What if the map depends on which somatic cell was sequenced?
It's not that geneticists have been unaware of variations between individuals of a species. Geneticists realize that sequencing the genome of Craig Venter or Desmond Tutu is not going to represent the human race. That's why multiple donors from different ethnic groups are included. The HapMap project seeks to characterize the extent of genetic variations in humans across the globe. That's old news. The new discovery is finding significant variation within an individual's own cells.
The repercussions of this discovery are unknown at this early stage. Stanford calls the differences between body cells "subtle." But remember, that's only between the skin cells that were analyzed by the research team. We won't really know how subtle -- or significant -- changes are between liver cells, brain cells, or cells of any given tissue or organ. If the differences remain subtle, nothing may come of it. Then again, this could be a game changer. Yale says:
The prevailing wisdom has been that every cell in the body contains identical DNA. However, a new study of stem cells derived from the skin has found that genetic variations are widespread in the body's tissues, a finding with profound implications for genetic screening, according to Yale School of Medicine researchers.One thing is clear at this stage: the assumption that each individual has a unique genome has been overthrown to some extent. Think how this might impact common evolutionary studies. For years, evolutionists have claimed small differences between human and chimpanzee genomes. What if the percent difference is a function of the source cells used? Remember, the Yale team found differences between cells in the same organ -- human skin. If the percent difference grows or shrinks depending on the source, any conclusions about human-chimp similarities would prove unreliable.
It's also not clear yet whether geneticists will be able to mask the differences between cells to establish an individual's genome (to say nothing of a species's genome) as a useful concept. Results would appear to be a function of investigator choice. Say, for instance, that an evolutionist chooses to compare genes of a particular kind of blood cell between species. If the CNV's and SNP's vary significantly from blood cell to blood cell within the individual, the results will be skewed. Mixing or averaging the maps of numerous cells, though, risks creating a theoretical construct that does not correspond to reality. Which cells should be averaged? Will the averages converge or diverge, depending on which cells are selected? Philosophers of science can have fun with this one.
Claims about evolutionary similarities and differences based on genetics must be taken with a grain of salt from now on. Perhaps the feared "profound implications" will prove inconsequential. If nothing else, though, the Yale study provides an example of conceptual superstructures built on shaky assumptions and "prevailing wisdom." As those of us in the intelligent design community know, what prevails at a given moment is not necessarily wise.