Professional bias

The featured picture from last week lab meeting is a figure from Justin’s presentation, made by Isabel. First, I like it because I am happy to see that trainees are collaborating! Second, it combines recombination hotspots with Cytochrome P450 (CYP) genes. It shows the fine-scale recombination rates, from genetic maps computed in different human populations from the 1000 Genomes data, in the CYP4F gene cluster.

Recombination is the process by which every child receives a unique mosaic of parental chromosomes. In most species, recombination occurs in narrow genomic segments, called recombination hotspots. My research until recently was mainly dedicated to the study of recombination hotspots, and the fascinating gene PRDM9, which I like to say is my favorite gene in the entire genome. It evolves very rapidly under strong positive selection, is implicated in disease, is critical for fertility. More recently, however, I have had another favorite gene family, the CYP genes. CYP enzymes are able to catalyze a considerable variety of oxidations for many structural classes of chemicals (including the majority of drugs), in all forms of life (bacteria, fungi, plants, birds, insect, reptiles and mammals). Similarly to PRDM9, they evolve quickly : these genes exhibit an exceptionally high number of mutations. Striking inter-individual and geographic differences in CYP allele frequencies are found in humans. The main hypothesis is that their evolution has first been influenced by interactions between animals and plants, and second, by diet and environmental pollutants impacting humans over thousands of years and differing between ethnic groups.

I am now fascinated by the evolution of these CYP families, but, by professional bias, let’s start by looking at the recombination landscape!

 

Further reading

Alves I, Houle AA, Hussin JG, Awadalla P. The impact of recombination on human mutation load and disease. Philos Trans R Soc Lond B Biol Sci. 2017 Dec 19;372(1736).

Paigen, K and Petkov P. PRDM9 and Its Role in Genetic Recombination. Trends in Genetics, 2018. 34(4): p.291-300.

Gonzalez, F.J. and D.W. Nebert, Evolution of the P450 gene superfamily: animal-plant ‘warfare’, molecular drive and human genetic differences in drug oxidation. Trends Genet, 1990. 6(6): p.182-6.

Nebert, D.W., Polymorphisms in drug-metabolizing enzymes: what is their clinical relevance and why do they exist? Am J Hum Genet, 1997. 60(2): p.265-71.

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