Targets Of Positive Selection Research Articles

Gene Conversion and the Evolution of Three Leucine-Rich Repeat Gene Families in Arabidopsis thaliana

The high number of duplicated genes in plant genomes provides a potential template for gene conversion and unequal crossing-over. Within a gene family these two processes can render all members homogeneous or generate diversity by reassorting variants among paralogs. The latter is especially feasible in families where gene diversity confers a selective advantage and thus conversion events are likely to be retained. Consequently, the most complete record of gene conversion is expected to be most evident in gene families commonly subjected to positive selection. Here, we describe the extent and characteristics of gene conversion and unequal crossing-over in the coding and noncoding regions of nucleotide-binding site leucine-rich repeat (NBS-LRR), receptor-like kinases (RLK), and receptor-like proteins (RLP) in the plant Arabidopsis thaliana. Members of these three gene families are associated with disease resistance and their pathogen-recognition domain is a documented target of positive selection. Our bioinformatic approach to study the major family features that may influence gene conversion revealed that in these families there is a significant association between the occurrence of gene conversion and high levels of sequence similarity, close physical clustering, gene orientation, and recombination rate. We discuss these results in the context of the overlap between gene conversion and positive selection during the evolutionary expansion of the NBS-LRR, RLK, and RLP gene families.

Nucleotide variability at the acetyl coenzyme A carboxylase gene and the signature of herbicide selection in the grass weed Alopecurus myosuroides (Huds.).

Acetyl coenzyme A carboxylase (ACCase) is the target of highly effective herbicides. We investigated the nucleotide variability of the ACCase gene in a sample of 18 black-grass (Alopecurus myosuroides [Huds.]) populations to search for the signature of herbicide selection. Sequencing 3,396 bp encompassing ACCase herbicide-binding domain in 86 individuals revealed 92 polymorphisms, which formed 72 haplotypes. The ratio of nonsynonymous versus synonymous substitutions was very low, in agreement with ACCase being a vital metabolic enzyme. Within black grass, most nonsynonymous substitutions were related to resistance to ACCase-inhibiting herbicides. Differentiation between populations was strong, in contrast to expectations for an allogamous, annual plant. Significant H tests revealed recent hitchhiking events within populations. These results were consistent with recent and local positive selection. We propose that, although they have only been used since at most 15 black-grass generations, ACCase-inhibiting herbicides have exerted a positive selection targeting resistant haplotypes that has been strong enough to have a marked effect upon ACCase nucleotide diversity. A minimum-spanning network of nonrecombinant haplotypes revealed multiple, independent apparitions of resistance-associated mutations. This study provides the first evidence for the signature of ongoing, recent, pesticide selection upon variation at the gene encoding the targeted enzyme in natural plant populations.

Positive Darwinian Selection at the Pantophysin (Pan I) Locus in Marine Gadid Fishes

Maximum-likelihood models of codon substitution were used to test for positive Darwinian selection at the vesicle protein pantophysin in two allelic lineages segregating in the Atlantic cod Gadus morhua and in 18 related species of marine gadid fishes. Positive selection was detected in the two intravesicular loops of the integral membrane protein but not in four membrane-spanning regions or the 3' cytoplasmic tail. The proportion of positively selected sites (24.9%) and the mean nonsynonymous/synonymous rate ratio (omega = d(N)/d(S) = 5.35) were both greater in the first intravesicular (IV1) domain compared with the second intravesicular (IV2) domain (11.0% positively selected sites with mean omega = 3.76). Likelihood ratio tests comparing models that assume identical omega ratios along all branches of the phylogeny to those that allow omega ratios to vary among lineages were not significant for either the IV1 or IV2 domains, indicating that the selective pressures favoring amino acid replacements have operated consistently in both regions during the diversification of the group. Positive selection was observed in the IV1 domain in both G. morhua allelic lineages, and, although three of the four codons that differ between alleles were targets of positive selection in the broader group, no similar polymorphisms were detected in other taxa. The two G. morhua Pan I alleles appeared to have evolved before the speciation event separating it from its sister taxon, Theragra chalcogramma, and on the basis of a standard mtDNA clock are estimated to be at least 2 Myr old. Although the function of pantophysin remains unknown, the strong signal of positive selection at specific sites in the IV1 and IV2 domains may help clarify its role in cellular trafficking pathways.

Positive selection and propeptide repeats promote rapid interspecific divergence of a gastropod sperm protein.

Male-specific proteins have increasingly been reported as targets of positive selection and are of special interest because of the role they may play in the evolution of reproductive isolation. We report the rapid interspecific divergence of cDNA encoding a major acrosomal protein of unknown function (TMAP) of sperm from five species of teguline gastropods. A mitochondrial DNA clock (calibrated by congeneric species divided by the Isthmus of Panama) estimates that these five species diverged 2-10 MYA. Inferred amino acid sequences reveal a propeptide that has diverged rapidly between species. The mature protein has diverged faster still due to high nonsynonymous substitution rates (> 25 nonsynonymous substitutions per site per 10(9) years). cDNA encoding the mature protein (89-100 residues) shows evidence of positive selection (Dn/Ds > 1) for 4 of 10 pairwise species comparisons. cDNA and predicted secondary-structure comparisons suggest that TMAP is neither orthologous nor paralogous to abalone lysin, and thus marks a second, phylogenetically independent, protein subject to strong positive selection in free-spawning marine gastropods. In addition, an internal repeat in one species (Tegula aureotincta) produces a duplicated cleavage site which results in two alternatively processed mature proteins differing by nine amino acid residues. Such alternative processing may provide a mechanism for introducing novel amino acid sequence variation at the amino-termini of proteins. Highly divergent TMAP N-termini from two other tegulines (Tegula regina and Norrisia norrisii) may have originated by such a mechanism.

A highly conserved sequence in the 3'-untranslated region of the drosophila Adh gene plays a functional role in Adh expression.

Phylogenetic analysis identified a highly conserved eight-base sequence (AAGGCTGA) within the 3'-untranslated region (UTR) of the Drosophila alcohol dehydrogenase gene, Adh. To examine the functional significance of this conserved motif, we performed in vitro deletion mutagenesis on the D. melanogaster Adh gene followed by P-element-mediated germline transformation. Deletion of all or part of the eight-base sequence leads to a twofold increase in in vivo ADH enzymatic activity. The increase in activity is temporally and spatially general and is the result of an underlying increase in Adh transcript. These results indicate that the conserved 3'-UTR motif plays a functional role in the negative regulation of Adh gene expression. The evolutionary significance of our results may be understood in the context of the amino acid change that produces the ADH-F allele and also leads to a twofold increase in ADH activity. While there is compelling evidence that the amino acid replacement has been a target of positive selection, the conservation of the 3'-UTR sequence suggests that it is under strong purifying selection. The selective difference between these two sequence changes, which have similar effects on ADH activity, may be explained by different metabolic costs associated with the increase in activity.

Positive Darwinian selection promotes charge profile diversity in the antigen-binding cleft of class I major-histocompatibility-complex molecules.

Certain major-histocompatibility-complex (MHC) loci are highly polymorphic, and the mechanism of maintenance of this polymorphism remains controversial. Recent studies of the pattern of nucleotide substitution at MHC loci have produced strong evidence that this polymorphism is maintained mainly by positive Darwinian selection that operates on the antigen recognition site (ARS) of the MHC molecule. The ARS of the class I MHC consists of three subregions: (1) the binding cleft, (2) T-cell-receptor-directed residues, and (3) outward-directed residues. Here we report that the rate of nonsynonymous nucleotide substitution is much higher in the binding cleft than in the other ARS subregions. Furthermore, nonsynonymous nucleotide substitutions that result in a change of residue side-chain charge occur significantly more frequently than expected by chance. We conclude that the main target of positive selection on the class I MHC molecules is the binding cleft of the ARS and that this selection acts primarily to promote diversity among alleles with respect to the pattern of residue side-chain charges (charge profile) in the binding cleft. These results provide additional support for the hypothesis that MHC polymorphism is maintained by overdominant selection relating to antigen-binding capacity and thus to disease resistance.