Biomedical subjects

S Boissinot

Publications and source records attributed to S Boissinot.

12 recordsLinked to original sources

PubMed2006

Human population genetic structure and diversity inferred from polymorphic L1(LINE-1) and Alu insertions.

BACKGROUND/AIMS: The L1 retrotransposable element family is the most successful self-replicating genomic parasite of the human genome. L1 elements drive replication of Alu elements, and both have had far-reaching impacts on the human genome. We use L1 and Alu insertion polymorphisms to analyze human population structure. METHODS: We genotyped 75 recent, polymorphic L1 insertions in 317 individuals from 21 populations in sub-Saharan Africa, East Asia, Europe and the Indian subcontinent. This is the first sample of L1 loci large enough to support detailed population genetic inference. We analyzed these data in parallel with a set of 100 polymorphic Alu insertion loci previously genotyped in the same individuals. RESULTS AND CONCLUSION: The data sets yield congruent results that support the recent African origin model of human ancestry. A genetic clustering algorithm detects clusters of individuals corresponding to continental regions. The number of loci sampled is critical: with fewer than 50 typical loci, structure cannot be reliably discerned in these populations. The inclusion of geographically intermediate populations (from India) reduces the distinctness of clustering. Our results indicate that human genetic variation is neither perfectly correlated with geographic distance (purely clinal) nor independent of distance (purely clustered), but a combination of both: stepped clinal.

Alu Elements↗

PubMed2005

Glycosylation of beet western yellows virus proteins is implicated in the aphid transmission of the virus.

Beet western yellows virus relies on the aphid M. persicae for its transmission in a persistent and circulative mode. To be transmitted, the virus must cross the midgut and the accessory salivary gland epithelial barriers by a transcytosis mechanism where vector receptors interact with virions. The aphid and the peptidic viral determinants implicated in this interaction mechanism have been studied. In this paper, we report that the coat and the readthrough proteins that constitute the capsid of this virus are glycosylated. Modification of the glucidic core of these structural viral proteins by oxidation with sodium metaperiodate or deglycosylation with N-glycosidase F or alpha-D-galactosidase abrogates the aphid transmission of the virus. Aphid transmission could also be inhibited by lectins directed against alpha-D-galactose when aphids were allowed to acquire virus on artificial membranes. These results suggest that the glucidic cores of the capsid proteins of beet western yellows virus contain alpha-D-galactose residues that are implicated in virus-aphid interaction and promote aphid transmission of the virus.

Amino Acid Sequence↗

PubMed2005

The structures of mouse and human L1 elements reflect their insertion mechanism.

L1 is an abundant, interspersed repeated DNA element of mammalian genomes. It has achieved its high copy number via retrotransposition. Like other non-LTR retrotransposons, L1 insertion into chromosomal DNA apparently occurs by target-site primed reverse transcription, or TPRT. L1 retrotransposition often generates elements with 5' truncations that are flanked by a duplication of the genomic target site (TSD). It is typically assumed that the 5' truncated elements are the consequence of poor processivity of the L1 reverse transcriptase. However, we find that the majority of young L1 elements from both the human and mouse genomes are truncated at sequences that can basepair with the target site. Thus, to whatever extent truncation is a consequence of poor processivity, we suggest that truncation is likely to occur when target site sequence can basepair with L1 sequence. This finding supports a model for insertion that occurs by two sequential TPRT reactions, the second of which relies upon the homology between the target site and L1. Because perfect heteroduplex formation is not required for all insertions, a dynamic relationship between the primer, template and enzyme during reverse transcription is inferred. 5' truncation may be a successful evolutionary strategy that is exploited by L1 as a means to escape host suppression of transposition.

Animals↗

PubMed2005

The recent evolution of human L1 retrotransposons.

L1 elements are the most successful retrotransposons in mammals and are responsible for at least 30% of human DNA. Far from being indolent genomic parasites, L1 elements have evolved and amplified rapidly during human evolution. Indeed during just the last 25 million years (MY) five distinct L1 families have emerged and generated tens of thousands of copies. The most recently evolved human specific L1 family is currently active and L1 copies have been accumulating in the human genome at about the same rate per generation as the currently active L1 families in Old World rats and mice. At times during the last 25 MY L1 activity constituted a significant enough genetic load to be subject to negative selection. During these same times, and in apparent response to the host, L1 underwent adaptive evolution. Understanding the molecular basis for these evolutionary changes should help illuminate one of the least understood but most important aspects of L1 biology, namely the extent and nature of the interaction between L1 and its host.

Evolution, Molecular↗

PubMed2001

Adaptive evolution in LINE-1 retrotransposons.

We traced the sequence evolution of the active lineage of LINE-1 (L1) retrotransposons over the last approximately 25 Myr of human evolution. Five major families (L1PA5, L1PA4, L1PA3B, L1PA2, and L1PA1) of elements have succeeded each other as a single lineage. We found that part of the first open-reading frame (ORFI) had a higher rate of nonsynonymous (amino acid replacement) substitution than synonymous substitution during the evolution of the ancestral L1PA5 through the L1PA3B families. This segment encodes the coiled coil region of the protein-protein interaction domain of the ORFI protein (ORFIp). Statistical analysis of these changes indicates that positive selection had been acting on this region. In contrast, the coiled coil segment hardly changed during the evolution of the L1PA3B to the present L1PA1 family. Therefore, selective pressure on the coiled coil segment has changed over time. We suggest that the fast rate of amino acid replacement in the coiled coil segment reflects the adaptation of L1 either to a changing genomic environment or to host repression factors. In contrast, the second open-reading frame and the nucleic acid-binding domain of the first open-reading frame are extremely well conserved, attesting to the strong purifying selection acting on these regions.

Amino Acid Sequence↗

PubMed2001

Selection against deleterious LINE-1-containing loci in the human lineage.

We compared sex chromosomal and autosomal regions of similar GC contents and found that the human Y chromosome contains nine times as many full-length (FL) ancestral LINE-1 (L1) elements per megabase as do autosomes and that the X chromosome contains three times as many. In addition, both sex chromosomes contain a ca. twofold excess of elements that are >500 bp but not long enough to be capable of autonomous replication. In contrast, the autosomes are not deficient in short (<500 bp) L1 elements or SINE elements relative to the sex chromosomes. Since neither the Y nor the X chromosome, when present in males, can be cleared of deleterious genetic loci by recombination, we conclude that most FL L1s were deleterious and thus subject to purifying selection. Comparison between nonrecombining and recombining regions of autosome 21 supported this conclusion. We were able to identify a subset of loci in the human DNA database that once contained active L1 elements, and we found by using the polymerase chain reaction that 72% of them no longer contain L1 elements in a representative of each of eight different ethnic groups. Genetic damage produced by both L1 retrotransposition and ectopic (nonallelic) recombination between L1 elements could provide the basis for their negative selection.

Chromosomes, Human, Pair 21↗

PubMed2000

L1 (LINE-1) retrotransposon evolution and amplification in recent human history.

L1 (LINE-1) elements constitute a large family of mammalian retrotransposons that have been replicating and evolving in mammals for more than 100 Myr and now compose 20% or more of the DNA of some mammals. Here, we investigated the evolutionary dynamics of the active human Ta L1 family and found that it arose approximately 4 MYA and subsequently differentiated into two major subfamilies, Ta-0 and Ta-1, each of which contain additional subsets. Ta-1, which has not heretofore been described, is younger than Ta-0 and now accounts for at least 50% of the Ta family. Although Ta-0 contains some active elements, the Ta-1 subfamily has replaced it as the replicatively dominant subfamily in humans; 69% of the loci that contain Ta-1 inserts are polymorphic for the presence or absence of the insert in human populations, as compared with 29% of the loci that contain Ta-0 inserts. This value is 90% for loci that contain Ta-1d inserts, which are the youngest subset of Ta-1 and now account for about two thirds of the Ta-1 subfamily. The successive emergence and amplification of distinct Ta L1 subfamilies shows that L1 evolution has been as active in recent human history as it has been found to be for rodent L1 families. In addition, Ta-1 elements have been accumulating in humans at about the same rate per generation as recently evolved active rodent L1 subfamilies.

3' Untranslated Regions↗

PubMed1998

Origins and antiquity of X-linked triallelic color vision systems in New World monkeys.

It is known that the squirrel monkey, marmoset, and other related New World (NW) monkeys possess three high-frequency alleles at the single X-linked photopigment locus, and that the spectral sensitivity peaks of these alleles are within those delimited by the human red and green pigment genes. The three alleles in the squirrel monkey and marmoset have been sequenced previously. In this study, the three alleles were found and sequenced in the saki monkey, capuchin, and tamarin. Although the capuchin and tamarin belong to the same family as the squirrel monkey and marmoset, the saki monkey belongs to a different family and is one of the species that is most divergent from the squirrel monkey and marmoset, suggesting the presence of the triallelic system in many NW monkeys. The nucleotide sequences of these alleles from the five species studied indicate that gene conversion occurs frequently and has partially or completely homogenized intronic and exonic regions of the alleles in each species, making it appear that a triallelic system arose independently in each of the five species studied. Nevertheless, a detailed analysis suggests that the triallelic system arose only once in the NW monkey lineage, from a middle wavelength (green) opsin gene, and that the amino acid differences at functionally critical sites among alleles have been maintained by natural selection in NW monkeys for >20 million years. Moreover, the two X-linked opsin genes of howler monkeys (a NW monkey genus) were evidently derived from the incorporation of a middle (green) and a long wavelength (red) allele into one chromosome; these two genes together with the (autosomal) blue opsin gene would immediately enable even a male monkey to have trichromatic vision.

Alleles↗

PubMed1998

Molecular genetics of spectral tuning in New World monkey color vision.

Although most New World monkeys have only one X-linked photopigment locus, many species have three polymorphic alleles at the locus. The three alleles in the squirrel monkey and capuchin have spectral peaks near 562, 550, and 535 nm, respectively, and the three alleles in the marmoset and tamarin have spectral peaks near 562, 556, and 543 nm, respectively. To determine the amino acids responsible for the spectral sensitivity differences among these pigment variants, we sequenced all exons of the three alleles in each of these four species. From the deduced amino acid sequences and the spectral peak information and from previous studies of the spectral tuning of X-linked pigments in humans and New World monkeys, we estimated that the Ala --> Ser, Ile --> Phe, Gly --> Ser, Phe --> Tyr, and Ala --> Tyr substitutions at residue positions 180, 229, 233, 277, and 285, respectively, cause spectral shifts of about 5, -2, -1, 8, and 15 nm. On the other hand, the substitutions His --> Tyr, Met --> Val or Leu, and Ala --> Tyr at positions 116, 275, and 276, respectively, have no discernible spectral tuning effect, though residues 275 and 276 are inside the transmembrane domains. Many substitutions between Val and Ile or between Val and Ala have occurred in the transmembrane domains among the New World monkey pigment variants but apparently have no effect on spectral tuning. Our study suggests that, in addition to amino acid changes involving a hydroxyl group, large changes in residue size can also cause a spectral shift in a visual pigment.

Amino Acid Substitution↗

PubMed1997

Mutation pattern variation among regions of the primate genome.

We sequenced three argininosuccinate-synthetase-processed pseudogenes (PsiAS-A1, PsiAS-A3, PsiAS-3) and their noncoding flanking sequences in human, orangutan, baboon, and colobus. Our data showed that these pseudogenes were incorporated into the genome of the Old World monkeys after the divergence of the Old World and New World monkey lineages. These pseudogene flanking regions show variable mutation rates and patterns. The variation in the G/C to A/T mutation rate (u) can account for the unequal GC contents at equilibrium: 34.9, 36.9, and 41.7% in the pseudogene PsiAS-A1, PsiAS-A3, and PsiAS-3 flanking regions, respectively. The A/T to G/C mutation rate (v) seems stable and the u/v ratios equal 1.9, 1.7, and 1.4 in the flanking regions of PsiAS-A1, PsiAS-A3, and PsiAS-3, respectively. These "regional" variations of the mutation rate affect the evolution of the pseudogenes, too. The ratio u/v being greater than 1.0 in each case, the overall mutation rate in the GC-rich pseudogenes is, as expected, higher than in their GC-poor flanking regions. Moreover, a "sequence effect" has been found. In the three cases examined u and v are higher (at least 20%) in the pseudogene than in its flanking region-i.e., the pseudogene appears as mutation "hot" spots embedded in "cold" regions. This observation could be partly linked to the fact that the pseudogene flanking regions are long-standing unconstrained DNA sequences, whereas the pseudogenes were relieved of selection on their coding functions only around 30-40 million years ago. We suspect that relatively more mutable sites maintained unchanged during the evolution of the argininosuccinate gene are able to change in the pseudogenes, such sites being eliminated or rare in the flanking regions which have been void of strong selective constraints over a much longer period. Our results shed light on (1) the multiplicity of factors that tune the spontaneous mutation rate and (2) the impact of the genomic position of a sequence on its evolution.

Animals↗

PubMed1997

Discordant phylogeographic patterns between the Y chromosome and mitochondrial DNA in the house mouse: selection on the Y chromosome?

We have compared patterns of geographic variation and molecular divergence of mitochondrial DNA (mtDNA) and Y chromosome over the range of the different subspecies of Mus musculus. MtDNA was typed for 305 nucleotides in the control region, the Y chromosome for 834 base pairs (bp) in Zfy introns and 242 bp in Sry, a Zfy2 18-bp deletion, and two microsatellites. Apparent discrepancies exist between the distributions of the lineages of mtDNA and of the two major Y-chromosome lineages thus defined: some subspecies share the same mtDNA lineage but have different Y-chromosome lineages or vice versa. One microsatellite reveals a geographically clustered variation inside the distribution of each Y-chromosome lineage, showing that new Y-chromosome variants can rapidly spread locally. The two major Y-chromosome lineages have a divergence time only about one fourth of that between mtDNA lineages. Although this recent coalescence of the Y chromosomes between subspecies could partly be due to a lower ancestral polymorphism of the Y chromosome, it suggests that secondary introgression after the radiation of the subspecies might have occurred. There is evidence that the differentiation of the Y-chromosome lineages contributes to partial reproductive isolation between subspecies, and patterns of molecular evolution suggest that selection has played a role in the rapid spread across subspecies.

Animals↗

PubMed1996

[Polytypic species Mus musculus in Transcaucasia].

It has been suggested that the house mouse, Mus musculus, is a polytypic species that originated in the northern part of the Indian sub-continent. Its subspecies have established secondary contact zones in east-centre China and in western Europe. However, the exact colonization routes taken by these subtaxa and their regions of primary differentiation have not yet been identified. We analyzed 89 mice from Transcaucasia at 35 enzyme loci and for polymorphism of the mitochondrial control region and a deletion of the Y chromosome. The various samples analyzed are a mosaic of populations intermediates between M. m. domesticus and M. m. musculus. Trancaucasia appears thus as a broad secondary contact zone, a fact which reinforces the idea that the species has retained large possibilities of remixing.

Animals↗