Biology subjects

Monget, P.

Publications and source records attributed to Monget, P..

3 recordsLinked to original sources

bioRxiv2025

Genes Encoding Xenobiotic Detoxification Proteins evolve by gene death, duplication and positive selection

There was a huge variability in the pharmacokinetics of drugs between species, which means in the way it will be transformed, degraded and eliminated, as well as the variation in drug absorption, plasma concentration over time, half-life, bioavailability, volume of distribution, metabolism rate, and routes of excretion. To understand the reasons of such a variability between species, we have studied here the evolution of genes encoding drug-metabolizing enzymes, i.e. the 9 key genes that are known to play a principal role in this process: UGT1A6, UGT1A, CYP2B, CYP2C, CYP2D, UGT2B, CYP3A, NAT1, GSTP1. We show here that a lot of these genes have been lost during evolution in several vertebrate species: UGT1A6 in gorilla, cat dog, ruminants, pig, UGT1A in artiodactyla, UGT2B in all vertebrate species except human and gorilla, CYP2C in all vertebrate species except primates and mouse. Several of these genes have duplicated such as UGT1A in human (4 copies), CYP3A in most of vertebrate species studied here except the cat, CYP2D in the mouse (9 copies). Furthermore, several of these genes undergone evolution by positive selection such as CYP2D6, UGT1A, CYP2C (particularly in squirrel), UGT1A. Overall, this study shows that the evolution by gene death, gene duplication, and positive selection is partly responsible for the great variability in the ability of vertebrate species to metabolize drugs.

evolutionary biology↗

bioRxiv2023

Sixteen oogenesin genes are dispensable for fertilityWhat is the significance of the dispensability of genes expressed in germ-cell?

Gene knockout experiments have shown that many genes are dispensable for a given biological function. The Oogenesin/Pramel family contains almost 85 paralogs, about thirty of which are specific to female (as well as male for some of them) germ cells. In this paper, we show that the deletion of a block of around 1Mb containing sixteen paralogous genes of the Oogenesin/Pramel family specific to germ cells, including Oogenesin-2, -3 and -4, has no consequences on fertility or prolificacy in mouse both sexes. The dispensability of these genes is probably due to the compensation by the other germ-cell specific paralogs.

molecular biology↗

bioRxiv2021

Genes encoding teleost orthologs of human haplo-insufficient and monoallelic genes remain in duplicate more frequently than the whole genome

Gene dosage is important is an important issue both in cell and evolutionary biology. Most genes are present in two copies in eukaryotic cells. The first outstanding exception is monoallelic gene expression (MA) that concerns genes localized on the X chromosome or in regions undergoing parental imprinting in eutherians, and many other genes scattered throughout the genome. The second exception concerns haploinsufficiency (HI), responsible for the fact that a single functional copy of a gene in a diploid organism is insufficient to ensure a normal biological function. One of the most important mechanisms ensuring functional innovation during evolution is Whole genome duplication (WGD). In addition to the two WGDs that have occurred in vertebrate genomes, the teleost genomes underwent an additional WGD, after their divergence from tetrapod. In the present work, we have studied on 57 teleost species whether the orthologs of human MA or HI genes remain more frequently in duplicates or returned more frequently in singleton than the rest of the genome. Our results show that the teleost orthologs of HI human genes remained more frequently in duplicate than the rest of the genome in all the teleost species studied. No signal was observed for the orthologs of genes localized on the human X chromosome or subjected to parental imprinting. Surprisingly, the teleost orthologs of the other human MA genes remained in duplicate more frequently than the rest of the genome for most teleost species. These results suggest that the teleost orthologs of MA and HI human genes also undergo selective pressures either related to absolute protein amounts and/or of dosage balance issues. However, these constraints seem to be different for MA genes in teleost in comparison with human genomes.

evolutionary biology↗