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Biomedical subjects

Hopi E Hoekstra

Publications and source records attributed to Hopi E Hoekstra.

7 recordsLinked to original sources

A single amino acid mutation contributes to adaptive beach mouse color pattern.

Natural populations of beach mice exhibit a characteristic color pattern, relative to their mainland conspecifics, driven by natural selection for crypsis. We identified a derived, charge-changing amino acid mutation in the melanocortin-1 receptor (Mc1r) in beach mice, which decreases receptor function. In genetic crosses, allelic variation at Mc1r explains 9.8% to 36.4% of the variation in seven pigmentation traits determining color pattern. The derived Mc1r allele is present in Florida's Gulf Coast beach mice but not in Atlantic coast mice with similar light coloration, suggesting that different molecular mechanisms are responsible for convergent phenotypic evolution. Here, we link a single mutation in the coding region of a pigmentation gene to adaptive quantitative variation in the wild.

Adaptation, Biological↗

Adaptive evolution of fertilization proteins within a genus: variation in ZP2 and ZP3 in deer mice (Peromyscus).

Rapid evolution of reproductive proteins has been documented in a wide variety of taxa. In internally fertilized species, knowledge about the evolutionary dynamics of these proteins between closely related taxa is primarily limited to accessory gland proteins in the semen of Drosophila. Investigation of additional taxa and functional classes of proteins is necessary in order to determine if there is a general pattern of adaptive evolution of reproductive proteins between recently diverged species. We performed an evolutionary analysis of 2 egg coat proteins, ZP2 and ZP3, in 15 species of deer mice (genus Peromyscus). Both of these proteins are involved in egg-sperm binding, a critical step in maintaining species-specific fertilization. Here, we show that Zp2 and Zp3 gene trees are not consistent with trees based on nonreproductive genes, Mc1r and Lcat, where species formed monophyletic clades. In fact, for both of the reproductive genes, intraspecific amino acid variation was extensive and alleles were sometimes shared across species. We document positive selection acting on ZP2 and ZP3 and identify specific amino acid sites that are likely targets of selection using both maximum likelihood approaches and patterns of parallel amino acid change. In ZP3, positively selected sites are clustered in and around the region implicated in sperm binding in Mus, suggesting changes may impact egg-sperm binding and fertilization potential. Finally, we identify lineages with significantly elevated rates of amino acid substitution using a Bayesian mapping approach. These findings demonstrate that the pattern of adaptive reproductive protein evolution found at higher taxonomic levels can be documented between closely related mammalian species, where reproductive isolation has evolved recently.

Adaptation, Biological↗

Signatures of reproductive isolation in patterns of single nucleotide diversity across inbred strains of mice.

Reproductive isolation is often caused by the disruption of genic interactions that evolve in geographically separate populations. Identifying the genomic regions and genes involved in these interactions, known as "Dobzhansky-Muller incompatibilities," can be challenging but is facilitated by the wealth of genetic markers now available in model systems. In recent years, the complete genome sequence and thousands of single nucleotide polymorphisms (SNPs) from laboratory mice, which are largely genetic hybrids between Mus musculus and M. domesticus, have become available. Here, we use these resources to locate genomic regions that may underlie reproductive isolation between these two species. Using genotypes from 332 SNPs that differ between wild-derived strains of M. musculus and M. domesticus, we identified several physically unlinked SNP pairs that show exceptional gametic disequilibrium across the lab strains. Conspecific alleles were associated in a disproportionate number of these cases, consistent with the action of natural selection against hybrid gene combinations. As predicted by the Dobzhansky-Muller model, this bias was differentially attributable to locus pairs for which one hybrid genotype was missing. We assembled a list of potential Dobzhansky-Muller incompatibilities from locus pairs that showed extreme associations (only three gametic types) among conspecific alleles. Two SNPs in this list map near known hybrid sterility loci on chromosome 17 and the X chromosome, allowing us to nominate partners for disrupted interactions involving these genomic regions for the first time. Together, these results indicate that patterns produced by speciation between M. musculus and M. domesticus are visible in the genomes of lab strains of mice, underscoring the potential of these genetic model organisms for addressing general questions in evolutionary biology.

Animals↗

Adaptive reptile color variation and the evolution of the Mc1r gene.

The wealth of information on the genetics of pigmentation and the clear fitness consequences of many pigmentation phenotypes provide an opportunity to study the molecular basis of an ecologically important trait. The melanocortin-1 receptor (Mc1r) is responsible for intraspecific color variation in mammals and birds. Here, we study the molecular evolution of Mc1r and investigate its role in adaptive intraspecific color differences in reptiles. We sequenced the complete Mc1r locus in seven phylogenetically diverse squamate species with melanic or blanched forms associated with different colored substrates or thermal environments. We found that patterns of amino acid substitution across different regions of the receptor are similar to the patterns seen in mammals, suggesting comparable levels of constraint and probably a conserved function for Mc1r in mammals and reptiles. We also found high levels of silent-site heterozygosity in all species, consistent with a high mutation rate or large long-term effective population size. Mc1r polymorphisms were strongly associated with color differences in Holbrookia maculata and Aspidoscelis inornata. In A. inornata, several observations suggest that Mc1r mutations may contribute to differences in color: (1) a strong association is observed between one Mc1r amino acid substitution and dorsal color; (2) no significant population structure was detected among individuals from these populations at the mitochondrial ND4 gene; (3) the distribution of allele frequencies at Mc1r deviates from neutral expectations; and (4) patterns of linkage disequilibrium at Mc1r are consistent with recent selection. This study provides comparative data on a nuclear gene in reptiles and highlights the utility of a candidate-gene approach for understanding the evolution of genes involved in vertebrate adaptation.

Adaptation, Physiological↗

Ecological genetics of adaptive color polymorphism in pocket mice: geographic variation in selected and neutral genes.

Patterns of geographic variation in phenotype or genotype may provide evidence for natural selection. Here, we compare phenotypic variation in color, allele frequencies of a pigmentation gene (the melanocortin-1 receptor, Mc1r), and patterns of neutral mitochondrial DNA (mtDNA) variation in rock pocket mice (Chaetodipus intermedius) across a habitat gradient in southern Arizona. Pocket mice inhabiting volcanic lava have dark coats with unbanded, uniformly melanic hairs, whereas mice from nearby light-colored granitic rocks have light coats with banded hairs. This color polymorphism is a presumed adaptation to avoid predation. Previous work has demonstrated that two Mc1r alleles, D and d, differ by four amino acids, and are responsible for the color polymorphism: DD and Dd genotypes are melanic whereas dd genotypes are light colored. To determine the frequency of the two Mc1r allelic classes across the dark-colored lava and neighboring light-colored granite, we sequenced the Mc1r gene in 175 individuals from a 35-km transect in the Pinacate lava region. We also sequenced two neutral mtDNA genes, COIII and ND3, in the same individuals. We found a strong correlation between Mc1r allele frequency and habitat color and no correlation between mtDNA markers and habitat color. Using estimates of migration from mtDNA haplotypes between dark- and light-colored sampling sites and Mc1r allele frequencies at each site, we estimated selection coefficients against mismatched Mc1r alleles, assuming a simple model of migration-selection balance. Habitat-dependent selection appears strong but asymmetric: selection is stronger against light mice on dark rock than against melanic mice on light rock. Together these results suggest that natural selection acts to match pocket mouse coat color to substrate color, despite high levels of gene flow between light and melanic populations.

Animals↗

The genetic basis of adaptive melanism in pocket mice.

Identifying the genes underlying adaptation is a major challenge in evolutionary biology. Here, we describe the molecular changes underlying adaptive coat color variation in a natural population of rock pocket mice, Chaetodipus intermedius. Rock pocket mice are generally light-colored and live on light-colored rocks. However, populations of dark (melanic) mice are found on dark lava, and this concealing coloration provides protection from avian and mammalian predators. We conducted association studies by using markers in candidate pigmentation genes and discovered four mutations in the melanocortin-1-receptor gene, Mc1r, that seem to be responsible for adaptive melanism in one population of lava-dwelling pocket mice. Interestingly, another melanic population of these mice on a different lava flow shows no association with Mc1r mutations, indicating that adaptive dark color has evolved independently in this species through changes at different genes.

Adaptation, Physiological↗