Biomedical subjects

Adel Khelifi

Publications and source records attributed to Adel Khelifi.

3 recordsLinked to original sources

PubMed2006

GC content evolution of the human and mouse genomes: insights from the study of processed pseudogenes in regions of different recombination rates.

Processed pseudogenes are generated by reverse transcription of a functional gene. They are generally nonfunctional after their insertion and, as a consequence, are no longer subjected to the selective constraints associated with functional genes. Because of this property they can be used as neutral markers in molecular evolution. In this work, we investigated the relationship between the evolution of GC content in recently inserted processed pseudogenes and the local recombination pattern in two mammalian genomes (human and mouse). We confirmed, using original markers, that recombination drives GC content in the human genome and we demonstrated that this is also true for the mouse genome despite lower recombination rates. Finally, we discussed the consequences on isochores evolution and the contrast between the human and the mouse pattern.

Animals↗

PubMed2005

Homology-dependent methylation in primate repetitive DNA.

In mammals, several studies have suggested that levels of methylation are higher in repetitive DNA than in nonrepetitive DNA, possibly reflecting a genome-wide defense mechanism against deleterious effects associated with transposable elements (TEs). To analyze the determinants of methylation patterns in primate repetitive DNA, we took advantage of the fact that the methylation rate in the germ line is reflected by the transition rate at CpG sites. We assessed the variability of CpG substitution rates in nonrepetitive DNA and in various TE and retropseudogene families. We show that, unlike other substitution rates, the rate of transition at CpG sites is significantly (37%) higher in repetitive DNA than in nonrepetitive DNA. Moreover, this rate of CpG transition varies according to the number of repeats, their length, and their level of divergence from the ancestral sequence (up to 2.7 times higher in long, lowly divergent TEs compared with unique sequences). This observation strongly suggests the existence of a homology-dependent methylation (HDM) mechanism in mammalian genomes. We propose that HDM is a direct consequence of interfering RNA-induced transcriptional gene silencing.

Animals↗

PubMed2005

HOPPSIGEN: a database of human and mouse processed pseudogenes.

Processed pseudogenes result from reverse transcribed mRNAs. In general, because processed pseudogenes lack promoters, they are no longer functional from the moment they are inserted into the genome. Subsequently, they freely accumulate substitutions, insertions and deletions. Moreover, the ancestral structure of processed pseudogenes could be easily inferred using the sequence of their functional homologous genes. Owing to these characteristics, processed pseudogenes represent good neutral markers for studying genome evolution. Recently, there is an increasing interest for these markers, particularly to help gene prediction in the field of genome annotation, functional genomics and genome evolution analysis (patterns of substitution). For these reasons, we have developed a method to annotate processed pseudogenes in complete genomes. To make them useful to different fields of research, we stored them in a nucleic acid database after having annotated them. In this work, we screened both mouse and human complete genomes from ENSEMBL to find processed pseudogenes generated from functional genes with introns. We used a conservative method to detect processed pseudogenes in order to minimize the rate of false positive sequences. Within processed pseudogenes, some are still having a conserved open reading frame and some have overlapping gene locations. We designated as retroelements all reverse transcribed sequences and more strictly, we designated as processed pseudogenes, all retroelements not falling in the two former categories (having a conserved open reading or overlapping gene locations). We annotated 5823 retroelements (5206 processed pseudogenes) in the human genome and 3934 (3428 processed pseudogenes) in the mouse genome. Compared to previous estimations, the total number of processed pseudogenes was underestimated but the aim of this procedure was to generate a high-quality dataset. To facilitate the use of processed pseudogenes in studying genome structure and evolution, DNA sequences from processed pseudogenes, and their functional reverse transcribed homologs, are now stored in a nucleic acid database, HOPPSIGEN. HOPPSIGEN can be browsed on the PBIL (Pole Bioinformatique Lyonnais) World Wide Web server (http://pbil.univ-lyon1.fr/) or fully downloaded for local installation.

Animals↗