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.

Abstract. Genetic isolation by distance (IBD) has rarely been described in marine species with high potential for dispersal at both the larval and adult life‐history stages. Here, we report significant relationships between inferred levels of gene flow and geographic distance in the Atlantic cod, Gadus morhua, at 10 nuclear restriction‐fragment‐length‐polymorphism (RFLP) loci at small regional scales in the western north Atlantic region (< 1600 km) that mirror those previously detected over its entire geographic range (up to 7300 km). Highly significant allele frequency differences were observed among eight northwestern Atlantic populations, although the mean FST for all 10 loci was only 0.014. Despite this weak population structuring, the distance separating populations explained between 54% and 62% of the variation in gene flow depending on whether nine or 10 loci were used to estimate Nm. Across the species' entire geographic range, highly significant differences were observed among six regional populations at nine of the 10 loci (mean FST= 0.068) and seven loci exhibited significant negative relationships between gene flow and distance. At this large geographic scale, natural selection acting in the vicinity of one RFLP locus (GM798) had a significant effect on the correlation between gene flow and distance, and eliminating it from the analysis caused the coefficient of determination to increase from 17% to 62%. The role of vicariance was assessed by sequentially removing populations from the analysis and was found to play a minor role in contributing to the relationship between gene flow and distance at either geographic scale. The correlation between gene flow and distance detected in G. morhua at small and large spatial scales suggests that dispersal distances and effective population sizes are much smaller than predicted for the species and that the recent age of populations, rather than extensive gene flow, may be responsible for its weak population structure. Our results suggest that interpreting limited genetic differences among populations as reflecting high levels of ongoing gene flow should be made with caution.

We tested for genetic differentiation among six populations of California sea mussels (Mytilus californianus) sampled across 4000 km of its geographical range by comparing patterns of variation at four independent types of genetic markers: allozymes, single-copy nuclear DNA markers, and DNA sequences from the male and female mitochondrial genomes. Despite our extensive sampling and genotyping efforts, we detected no significant differences among localities and no signal of isolation by distance suggesting that M. californianus is genetically homogeneous throughout its range. This concordance differs from similar studies on other mytilids, especially in the role of postsettlement selection generating differences between exposed coastal and estuarine habitats. To assess if this homogeneity was due to M. californianus not inhabiting estuarine environments, we reviewed studies comparing allozymes with other classes of nuclear DNA markers. Although both types of markers gave broadly consistent results, there was a bias favouring studies in which allozymes were more divergent than DNA markers (nine to three) and a disproportionate number of these cases involved marine taxa (seven). Furthermore, allozymes were significantly more heterogeneous than DNA markers in three of the four studies that sampled coastal and estuarine habitats. We conclude that the genetic uniformity exhibited by M. californianus may result from a combination of extensive gene flow and the lack of exposure to strong selective gradients across its range.

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The swarm of quasispecies that evolves in each HIV-1-infected individual represents a source of closely related Env protein variants that can be used to explore various aspects of HIV-1 biology. In this study, we made use of these variants to identify mutations that confer sensitivity and resistance to the broadly neutralizing antibodies found in the sera of selected HIV-1-infected individuals. For these studies, libraries of Env proteins were cloned from infected subjects and screened for infectivity and neutralization sensitivity. The nucleotide sequences of the Env proteins were then compared for pairs of neutralization-sensitive and -resistant viruses. In vitro mutagenesis was used to identify the specific amino acids responsible for the neutralization phenotype. All of the mutations altering neutralization sensitivity/resistance appeared to induce conformational changes that simultaneously enhanced the exposure of two or more epitopes located in different regions of gp160. These mutations appeared to occur at unique positions required to maintain the quaternary structure of the gp160 trimer, as well as conformational masking of epitopes targeted by neutralizing antibodies. Our results show that sequences in gp41, the CD4 binding site, and the V2 domain all have the ability to act as global regulators of neutralization sensitivity. Our results also suggest that neutralization assays designed to support the development of vaccines and therapeutics targeting the HIV-1 Env protein should consider virus variation within individuals as well as virus variation between individuals.