Conversation with Francesc Calafell. Part 1

The genome, the individual, the family, the population. Today we are going to tackle the study of the genome mainly in a tiny part of it but extremely interesting, what we are going to call the uniparental markers. And for that we have with us today Francesc Calafell. Francesc Calafell is associate professor at Pompeu Fabra University and principal investigator of the Institute of Evolutionary Biology in Barcelona. He did the PhD in Barcelona, moved to Torino in Italy and Yale in USA, and then back to Barcelona. His lab is interested in the genomic studies that go from the individual to the population.

It has been involved in many different studies using uniparental markers both mitochondrial DNA and Y chromosome to unravel the population history but also to lower levels, levels of families of groups of individuals to understand the microevolutionary patterns. So, in this interview we are going to try to understand the importance of this kind of markers, this kind of fractions of our genome that will help us to understand many things from ourselves, from our family and from the population we come from. Francesc, why the uniparental markers are so interesting and so much effort has been devoted to them?

Because it’s the only part of the genome in which we are certain that what we are seeing, we know which parent it came from. In the case of the Y chromosome we know that it came from the father, in the case of mitochondrial DNA it came from the mother. The rest of the genome is a mixture of both parents. So, we can iterate this and it came from the father in the case of the Y chromosome but all from the paternal grandfather, from the great grandfather and so on and so forth. And the only changes that accumulate in the Y chromosome and in mitochondrial DNA are due to mutation.

So it is extremely easy compared to the rest of the genome to construct phylogenetic trees with uniparental markers. Both for the mitochondria and for the Y chromosome? Yes. Although there are genetic markers that evolve with different speeds in both of them. So, in some cases –particular in the Y chromosome and regions called Short Tandem Repeats – it would be difficult to build a phylogenetic tree of them but for most of the variations of Y chromosome and for the mitochondrial DNA, yes, you can easily reconstruct a phylogenetic tree. How would you study for example mitochondrial DNA of an individual, myself? It depends on how much money you give me.

If you give me little money or if we go back ten or twenty years I would sequence the so called hypervariable region. Then, given that first no recombination in mitochondrial DNA, it also carries information about the rest of the molecule. With the current technologies it’s becoming cheaper and cheaper and just to sequence everything which in the case of mitochondrial DNA is just sixteen and a half kilo bases, that’s less than one millionth of the size of the entire genome. Sixteen thousand base pairs for the whole mitochondria, a tiny fraction. For the Y, what would you do then? The Y is larger and much more complicated technically and it is feasible to sequence the entire Y chromosome.

There are even commercial companies that if you send them a sample of say, saliva and a check they would sequence it for you but still there’s plenty of room for genotyping just say between ten and a hundred Short Tandem Repeats in the whole of the Y chromosome.