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La “Nature” ne jette pas les dés, “Elle” joue au Légo et au billard: création de
gènes chimères et évolution du cerveau humain //
"Nature" does not cast the dice, "she" plays lego and billiards: chimaeric
gene creation and human brain evolution| old_uid | 10442 |
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| title | La “Nature” ne jette pas les dés, “Elle” joue au Légo et au billard: création de
gènes chimères et évolution du cerveau humain //
"Nature" does not cast the dice, "she" plays lego and billiards: chimaeric
gene creation and human brain evolution |
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| start_date | 2011/11/25 |
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| schedule | 14h30 |
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| online | no |
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| location_info | salle de séminaire |
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| summary | Among the traits that distinguish humans from other mammals are the relative size, organization and functions of the brain. The anatomical and physiological substrates underlying the unique features of the human behavior have been extensively studied while our knowledge of the genetic changes associated with their emergence remained elusive for decades. The first publication of the almost complete human genomes in 2001, followed by the chimp genome in 2004 opened the era of genome-wide comparisons with a powerful resolution. The search for primate-specific genes and genomic-features linked to human brain
evolution provides insights into three main directions I propose to follow during my presentation: 1) the speed of divergence of brain-expressed gene sequences in the human lineage; 2) changes in gene expression among primates, and the sequences of regulatory elements, that could play a major role in adaptive evolution; 3) emergence or deletion of genes that have contributed to the evolution of the human brain structure and function. In this context, we provided the first evidence for the emergence of two chimaeric genes in Hominids. These genes were named PMCHL1 and PMCHL2 based on partial homology with the PMCH gene encoding the melanin-concentrating hormone (MCH), a neuropeptide involved in energy homeostasis. Phylogenetic analyses showed that the PMCHL1 gene was created about 32 million years ago (Mya) by a complex “Lego-like” mechanism involving MCH antisense mRNA retrotransposition while PMCHL2 arose 5-10 Mya through segmental duplication. These chimaeric genes have been submitted to strong regulatory constraints during primate evolution. Indeed, emergence of new exons and new cis-regulatory sequences resulted in different expression patterns of PMCHL1 sense and antisense RNAs in the primate brain. Most of these transcripts are non-coding RNAs and could target either PMCH itself or genes that could alter MCH signaling, offering multiple players for a fascinating “billiard game” we are trying to understand. Strikingly, the creation of novel genes during human evolution is not a rare event. Many primate-specific genes have been found often located in chromosomal domains called “gene nurseries” and they provide further raw material for gene innovation that potentially underlied human brain evolution.
This work was supported by the CNRS (INSB), a EU contract (APES) and an ANR-MNP contract. |
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| responsibles | Riehle |
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