Trustee, California Academy of Sciences (1997 - Present)
President, California Academy of Sciences (2003 - Present)
PhD, Yale University, Biology (1967)
MS, Yale University, Biology (1964)
BA, Yale University, Scholar of the House (Zoology) (1962)
Current Research and Scholarly Interests
Evolutionary adaptive mechanisms, molecules to ecosystems
Independent Studies (2)
- Advanced Research Laboratory in Experimental Biology
BIO 199 (Sum)
- Directed Reading in Biology
BIO 198 (Sum)
- Advanced Research Laboratory in Experimental Biology
Graduate and Fellowship Programs
Biology (School of Humanities and Sciences) (Phd Program)
Specific-gene studies of evolutionary mechanisms in an age of genome-wide surveying.
Annals of the New York Academy of Sciences
2013; 1289 (1): 1-17
The molecular tools of genomics have great power to reveal patterns of genetic difference within or among species, but must be complemented by the mechanistic study of the genetic variants found if these variants' evolutionary meaning is to be well understood. Central to this purpose is knowledge of the organisms' genotype-phenotype-environment interactions, which embody biological adaptation and constraint and thus drive natural selection. The history of this approach is briefly reviewed. Strategies embracing the complementarity of genomics and specific-gene studies in evolution are considered. Implementation of these strategies, and examples showing their feasibility and power, are discussed. Initial generalizations emphasize: (1) reproducibility of adaptive mechanisms; (2) evolutionary co-importance of variation in protein sequences and expression; (3) refinement of rudimentary molecular functions as an origin of evolutionary innovations; (4) identification of specific-gene mechanisms as underpinnings of genomic or quantitative genetic variation; and (5) multiple forms of adaptive or constraining epistasis among genes. Progress along these lines will advance understanding of evolution and support its use in addressing urgent medical and environmental applications.
View details for DOI 10.1111/nyas.12139
View details for PubMedID 23679204
Evolutionary genomics of Colias Phosphoglucose Isomerase (PGI) introns.
Journal of molecular evolution
2012; 74 (1-2): 96-111
Little is known of intron sequences' variation in cases where eukaryotic gene coding regions undergo strong balancing selection. Phosphoglucose isomerase, PGI, of Colias butterflies offers such a case. Its 11 introns include many point mutations, insertions, and deletions. This variation changes with intron position and length, and may leave little evidence of homology within introns except for their first and last few basepairs. Intron position is conserved between PGIs of Colias and the silkmoth, but no intron sequence homology remains. % GC content and length are functional properties of introns which can affect whole-gene transcription; we find a relationship between these properties which may indicate selection on transcription speed. Intragenic recombination is active in these introns, as in coding sequences. The small extent of linkage disequilibrium (LD) in the introns decays over a few hundred basepairs. Subsequences of Colias introns match subsequences of other introns, untranslated regions of cDNAs, and insect-related transposons and pathogens, showing that a diverse pool of sequence fragments is the source of intron contents via turnover due to deletion, recombination, and transposition. Like Colias PGI's coding sequences, the introns evolve reticulately with little phylogenetic signal. Exceptions are coding-region allele clades defined by multiple amino acid variants in strong LD, whose introns are closely related but less so than their exons. Similarity of GC content between introns and flanking exons, lack of small introns despite mutational bias toward deletion, and findings already mentioned suggest constraining selection on introns, possibly balancing transcription performance against advantages of higher recombination rate conferred by intron length.
View details for DOI 10.1007/s00239-012-9492-5
View details for PubMedID 22388354
Emergence of Complex Haplotypes from Microevolutionary Variation in Sequence and Structure of Colias Phosphoglucose Isomerase
JOURNAL OF MOLECULAR EVOLUTION
2009; 68 (5): 433-447
A molecular evolutionary explanation of natural genetic variation requires analysis of specific variants' evolutionary dynamics. To pursue this for phosphoglucose isomerase (PGI) of Colias butterflies, whose polymorphism is maintained by strong natural selection, we assembled a large data set of wild haplotypes, highly variable at the amino acid and DNA levels. The most common electrophoretic, i.e., charge macrostate, allele class, 3, is conserved in its pattern of charged amino acid residues. The next most common macrostate, 4, has multiple patterns of charge, i.e., microstates, while less common (1, 2, 5, 6) macrostates are very diverse. Macrostate 4 shows significant linkage disequilibrium (LD) among its variants, especially for two groups of five haplotypes each. We find extensive intragenic recombination among all haplotypes except the two high-LD groups of macrostate 4, which display none. Phyletic relations among haplotypes are largely reticulate, again except for the high-LD groups of macrostate 4, which form clades with strong bootstrap support. Charge-changing and linked charge-neutral amino acid variants occur in diverse parts of PGI's sequence. Homology-based modeling of PGI's structure shows that these regions are related spatially in ways suggesting functional interaction. The high-LD groups of macrostate 4 display parallel amino acid variation in these regions. This pattern of haplotype clades with high LD among multiple varying sites, emerging from chaotically recombining variation, may be a "signature" of refinement of complex adaptive sequences by recombination and selection. It should be tested further in this study system and others as a possibly general feature of the evolution of living complexity.
View details for DOI 10.1007/s00239-009-9237-2
View details for Web of Science ID 000266482400001
View details for PubMedID 19424742
A mitochondrial-DNA-based phylogeny for some evolutionary-genetic model species of Colias butterflies (Lepidoptera, Pieridae)
MOLECULAR PHYLOGENETICS AND EVOLUTION
2008; 47 (3): 893-902
We study the phylogenetic relationships among some North American Colias ("sulfur") butterflies, using mitochondrial gene sequences (ribosomal RNA, cytochrome oxidase I+II) totaling about 20% of the mitochondrial genome. We find that (1) the lowland species complex shows a branching order different from earlier views; (2) several montane and northern taxa may be more distinct than in earlier views; (3) one morphologically conservative Holarctic assemblage, C. hecla, is differentiated at the molecular-genetic level into at least three taxa which occupy distinct positions in the phylogeny and are sisters to diverse other taxa. These conclusions, constituting phylogenetic hypotheses, are supported by parsimony, maximum-likelihood, and Bayesian reconstruction algorithms. They are tested formally, by interior branch tests and paired-site tests, against alternative hypotheses derived from conventional species and subspecies naming combinations. In all cases our hypotheses are supported by these tests and the conventional alternatives are rejected. The "barcoding" subset of cytochrome oxidase I sequence identifies only some of the taxa supported by our full data set. Comparison of genetic divergence values among Colias taxa with those among related Pierid butterflies suggests that species radiations within Colias are comparatively younger. This emerging Colias phylogeny facilitates comparisons of genetic polymorphism and other adaptive mechanisms among taxa, thereby connecting micro- and macro-evolutionary processes.
View details for DOI 10.1016/j.ympev.2008.03.013
View details for Web of Science ID 000257128900002
View details for PubMedID 18442929
From DNA to fitness differences: Sequences and structures of adaptive variants of Colias phosphoglucose isomerase (PGI)
MOLECULAR BIOLOGY AND EVOLUTION
2006; 23 (3): 499-512
Colias eurytheme butterflies display extensive allozyme polymorphism in the enzyme phosphoglucose isomerase (PGI). Earlier studies on biochemical and fitness effects of these genotypes found evidence of strong natural selection maintaining this polymorphism in the wild. Here we analyze the molecular features of this polymorphism by sequencing multiple alleles and modeling their structures. PGI is a dimer with rotational symmetry. Each monomer provides a critical residue to the other monomer's catalytic center. Sequenced alleles differ at multiple amino acid positions, including cryptic charge-neutral variation, but most consistent differences among the electromorph alleles are at the charge-changing amino acid sites. Principal candidate sites of selection, identified by structural and functional analyses and by their variants' population frequencies, occur in interpenetrating loops across the interface between monomers, where they may alter subunit interactions and catalytic center geometry. Comparison to a second (and basal) species, Colias meadii, also polymorphic for PGI under natural selection, reveals one fixed amino acid difference between their PGIs, which is located in the interpenetrating loop and accompanies functional differences among their variants. We also study nucleotide variability among the PGI alleles, comparing these data to similar data from another glycolytic enzyme gene, glyceraldehyde-3-phosphate dehydrogenase. Despite extensive nonsynonymous and synonymous polymorphism at PGI in each species, the only base changes fixed between species are the two causing the amino acid replacement; this absence of synonymous fixation yields a significant McDonald-Kreitman test. Analyses of these data suggest historical population expansion. Positive peaks of Tajima's D statistic, representing regions of neutral "hitchhiking," are found around the principal candidate sites of selection. This study provides novel views of molecular-structural mechanisms, and beginnings of historical evidence, for a long-persistent balanced enzyme polymorphism at PGI in these and perhaps other species.
View details for DOI 10.1093/molbev/msj062
View details for Web of Science ID 000235610300004
View details for PubMedID 16292000
View details for PubMedCentralID PMC2943955
- A reconnaissance of population genetic variation in arctic and subarctic sulfur butterflies (Colias spp.; Lepidoptera, Pieridae) CANADIAN JOURNAL OF ZOOLOGY-REVUE CANADIENNE DE ZOOLOGIE 2005; 83 (12): 1614-1623
Adaptation at specific loci. VII. Natural selection, dispersal and the diversity of molecular-functional variation patterns among butterfly species complexes (Colias : Lepidoptera, Pieridae)
2003; 12 (5): 1265-1275
Natural genetic variants at the phosphoglucose isomerase, PGI, gene differ in spatial patterning of their polymorphism among species complexes of Colias butterflies in North America. In both lowland and alpine complexes, molecular-functional properties of the polymorphic genotypes can be used to predict genotype-specific adult flight performances and resulting large genotypic differences in adult fitness components. In the lowland species complex, there is striking uniformity of PGI polymorph frequencies at a number of sites across the American West; this fits with earlier findings of strong, similar differences in fitness components over this range. In an alpine complex, Colias meadii shows similar uniformity of PGI frequencies within habitat types, either montane steppe or alpine tundra, over several hundred kilometres in the absence of dispersal. At the same time, large shifts (10-20%) in frequency of the most common alleles occur between steppe and tundra populations, whether these are isolated or, as in some cases, are in contact and exchange many dispersing adults each generation. Data on male mating success of common C. meadii PGI genotypes in steppe and tundra show heterozygote advantage in both habitat types, with shifts in relative homozygote disadvantage between habitats which are consistent with observed frequency differences. Nonadaptive explanations for this situation are rejected, and alternative, thermal-ecology-based adaptive hypotheses are proposed for later experimental test. These findings show that strong local selection may dominate dispersal as an evolutionary agent, whether or not dispersal is present, and that selection may often be the major force promoting 'cohesion' of species over long distances. This case offers new opportunities for integrating studies of molecular structure and function with ecological aspects of natural selection in the wild, both within and among species.
View details for Web of Science ID 000182261500015
View details for PubMedID 12694289
Molecular-functional studies of adaptive genetic variation in prokaryotes and eukaryotes
ANNUAL REVIEW OF GENETICS
2000; 34: 593-622
Knowledge of both prokaryotic and eukaryotic organisms is essential to the study of molecular evolution. Their common ancestry mandates that their molecular functions share many aspects of adaptation and constraint, yet their differences in size, ploidy, and structural complexity also give rise to divergent evolutionary options. We explore the interplay of adaptation, constraint, and neutrality in their evolution by the use of genetic variants to probe molecular function in context of molecular structure, metabolic organization, and phenotype-environment interactions. Case studies ranging from bacteria to butterflies, flies, and vertebrates emphasize, among other points: the importance of moving from initial recording of evolutionary pattern variation to studying the processes underlying the patterns, by experiment, reconstructive inference, or both; the complementarity, not conflict, of finding different performance and fitness impacts of natural variants in prokaryotes or eukaryotes, depending on the nature and magnitude of the variants, their locations and roles in pathways, the nature of molecular function affected, and the resulting organismal phenotype-environment interactions leading to selection or its absence; the importance of adaptive functional interaction of different kinds of variants, as in gene expression variants versus variants altering polypeptide properties, or interaction of changes in enzymes' active sites with complementary changes elsewhere that adjust catalytic function in different ways, or coadaptation of different steps' properties in pathways; the power afforded by combining structural and functional analyses of variants with study of the variants' phenotype-environment interactions to understand how molecular changes affect (or fail to affect) adaptive mechanisms "in the wild." Comparative study of prokaryotes and eukaryotes in this multifaceted way promises to deliver both new insights into evolution and a host of new and productive questions about it.
View details for Web of Science ID 000166299400021
View details for PubMedID 11092840
Flight-muscle adenylate pool responses to flight demands and thermal constraints in individual Colias eurytheme (Lepidoptera, Pieridae)
JOURNAL OF EXPERIMENTAL BIOLOGY
1999; 202 (22): 3145-3154
We study here the connections among body temperature variation, flight performance and flight 'fuel' metabolism in Colias eurytheme butterflies, to begin re-examining the metabolic reasons for animal thermoregulation. Methods are presented for (a) stable extraction of adenylates (and other metabolites) from the flight muscles of individual Colias eurytheme, (b) automated separation and quantitative analysis of individual adenylate samples by high-pressure liquid chromatography and (c) reliable, low-variance assay of inorganic phosphate levels in the same extracts. Correlations among metabolite concentrations and two indices of muscle cytosol ATP maintenance occur as expected on general metabolic principles. [ATP] and [ATP]/[ADP] decline from resting levels to reach a plateau in the first minute of free, interrupted flight, while [AMP] increases at the same time; these concentrations do not vary further for up to 6 min total flight time. In an initial test of the alternative metabolic bases of the thermoregulation of Colias eurytheme, we find that [ATP]/[ADP] rises between a body temperature, T(b), of 31 and 35 degrees C, at the base of the behavioral thermal optimum for flight, but then decreases again at T(b)=39 degrees C, at the top of the behavioral thermal optimum and well short of damaging temperatures. This is not consistent with the view that metabolic effectiveness increases monotonically up to the lower limits of thermal damage to enzymes, but supports an alternative hypothesis that the narrowness of thermoregulation results from a system-based constraint on the breadth of temperature over which maximal energy processing is possible.
View details for Web of Science ID 000084295000011
View details for PubMedID 10539963
Adenylate levels and environmental stress in the sea anemone Anthopleura elegantissima.
Molecular marine biology and biotechnology
1994; 3 (5): 261-269
The tissue concentrations of adenosine nucleotides in the sea anemone Anthopleura elegantissima were determined during laboratory manipulations simulating natural environmental stresses: desiccation at low and high air temperatures, increased seawater temperature, mechanical disturbance causing column contraction, and starvation. The levels of adenylates significantly decreased during anemone desiccation, column contraction, and starvation. Variations in adenylate energy charge, the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and the ratio of ATP to total adenylates were compared with changes in absolute adenylate concentrations to determine the usefulness of these ratios in indicating changes in metabolic activity and physiological stress. The changes in the adenylate levels were far greater than the changes in adenylate ratios. The usefulness of adenylate energy charge, or the other adenylate ratios, as single or exclusive indices of metabolic stress in A. elegantissima is questionable, given these results. Changes in absolute adenylate levels do indicate significant metabolic changes in the anemones associated with desiccation, column contraction, and starvation.
View details for PubMedID 7881513
- ALLOZYMES IN EVOLUTIONARY GENETICS - SELF-IMPOSED BURDEN OR EXTRAORDINARY TOOL GENETICS 1994; 136 (1): 11-16
ADAPTATION AT SPECIFIC LOCI .3. FIELD BEHAVIOR AND SURVIVORSHIP DIFFERENCES AMONG COLIAS PGI GENOTYPES ARE PREDICTABLE FROM INVITRO BIOCHEMISTRY
1983; 103 (4): 725-739
Previous work on the phosphoglucose isomerase (PGI) polymorphism of Colias butterflies led to predictions concerning aspects of differential survivorship and fecundity among the polymorphic genotypes in the wild. Explicit assumptions underlying these predictions were that functional differences among genotypes at the in vitro biochemical level reflected roughly corresponding differences in vivo, and that the interaction of such differences with the thermal dependence of flight capacity was correctly understood. All those predictions tested were confirmed. We now report experimental designs for testing three more of these predictions. They concern both differential survivorship and the flight activity component of differential fecundity. We find, as predicted: (1) certain heterozygotes, kinetically most effective at low temperature, begin flight earlier in the day than do other genotypes (six replicates); (2) among the three most common genotypes, the order of kinetic effectiveness, i.e., 3/4 > 3/3 > 4/4, is reflected in asymmetric order of heterotic advantage, 3/4 > 3/3 > 4/4, in time of flight initiation, breadth of flight time and/or overall flight density through the day (six replicates); (3) under high temperature stress, the usual survivorship advantage of kinetically favored genotypes is reversed, and the three most thermally stable genotypes show better survivorship.--These results strengthen further the case for direct natural selection on this locus. Implications for population sampling practices, for studies of the adaptive organization of metabolism, and for studies of the interaction of genetic variation with patterns of environmental variability are discussed.
View details for Web of Science ID A1983QP15300010
View details for PubMedID 17246122
ADAPTATION AT SPECIFIC LOCI .2. DEMOGRAPHIC AND BIOCHEMICAL-ELEMENTS IN THE MAINTENANCE OF THE COLIAS PGI POLYMORPHISM
1983; 103 (4): 691-724
Demographically oriented sampling in the wild and biochemical study of allozymes in the laboratory have been used to probe maintenance of the phosphoglucose isomerase polymorphism of Colias butterflies.-The several alleles at this locus show negative or no covariation among their frequencies in the wild. This rules out Wahlund effects as a cause of observations of heterozygote excess at this locus in broods that fly as single cohorts. Unusually heavy mortality among adults, due to drought stress or other causes, can preclude manifestation of differential survivorship among phosphoglucose isomerase genotypes. In broods composed of overlapping cohorts, heterozygote deficiency, apparently due to Wahlund effects in time as cohorts of different survivorship experience mix, can be found. Heterozygotes at this locus fly under a broader range of weather conditions than other genotypes.-Previously detected kinetic differentiation among the genotypes extends in greater magnitude to the glycolytic reaction direction, as well as to a broader range of test conditions than examined before. The heterozygote 3/4 is strikingly heterotic for several measures of kinetic functional effectiveness. Other heterozygotes are sometimes heterotic, more often intermediate (but not exactly so, nor additive in any sense) in properties between homozygotes.-Predictions are made from the biochemical analysis and from the insects' thermal ecology concerning distributions of the genotypes in the wild. Some agree with facts already established. Others are tested and confirmed from data already on hand. Still others are to be tested as reported in an accompanying paper.-All available evidence points to a combination of heterozygote advantage and fluctuating-environment selection as responsible for maintaining this polymorphism. There is considerable evidence for the operation of protein-structural constraint on the range of adaptations possible at this locus.
View details for Web of Science ID A1983QP15300009
View details for PubMedID 17246121
METABOLIC RESOURCE-ALLOCATION VS MATING ATTRACTIVENESS - ADAPTIVE PRESSURES ON THE ALBA POLYMORPHISM OF COLIAS BUTTERFLIES
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
1980; 77 (6): 3615-3619
The sex-limited "alba" genetic polymorphism in wing color of Colias butterflies has been studied with respect to potential selective pressures on this locus. Alba female pupae, carrying at least one dominant A allele, redirect resources, used by aa pupae for pigmentation, to other metabolic ends. Associated with this reallocation, alba, A-, female adults eclose earlier, retain more larva-derived resources in their fat bodies for somatic maintenance and for reproduction, and, in some conditions, mature their eggs faster than do aa females. Alba females are also less attractive to males than are aa females and mate less frequently. Evolutionary implications of these results are discussed.
View details for Web of Science ID A1980JY17400100
View details for PubMedID 16592842