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PubMed1992

Comparative life spans of species: why do species have the life spans they do?

Proximate answers to questions about species longevity are to be found in the physiological processes that regulate duration of life. But what are these processes, and how are they themselves controlled? This leads to ultimate, evolutionary questions about longevity. What are the selection forces that favor one life span instead of another for a given species? To understand the evolution of life span we need also to understand the evolution of aging. A plausible hypothesis is that because of the requirement for reproduction, natural selection favors a strategy that invests fewer resources in maintenance of somatic cells and tissues than are necessary for indefinite survival. This "disposable soma" theory predicts that aging is due to the accumulation of unrepaired somatic defects and the primary genetic control of longevity operates through selection to raise or lower the investment in basic cellular maintenance systems in relation to the level of environmental hazard.

Aging↗
PubMed1981

On the immortality of the germ line: genetic and biochemical mechanism. A review.

The nature of the differences between mortal somatic cells and immortal germ cell lines constitutes a major area of theoretical gerontology which has not yet received adequate attention. Weismann's theory, first stated almost exactly a century ago, was recently reconsidered by Kirkwood and Holliday. They applied modern concepts and findings on the factors regulating the accuracy of synthesis of macromolecules to explain germ line immortality. In the present paper, evidence on ageing of reproductive cells and the relationship of cytomorphogenetic events to periodic rejuvenation of germ cell lines is summarized and evaluated. Key events include the elimination or reversal of some DNA changes in germ cells through recombination and meiotic haploidization, cyclic regeneration of transcriptional and translational systems during gametogenesis and early development, and the selection of stable, viable genomes at various stages of the reproductive cycle. These rejuvenatory processes are compared and related to molecular events which differentiated somatic cells are unable to carry out.

Aging↗
PubMed1966

Immunoglobulin kappa-chains. Comparative sequences in selected stretches of Bence-Jones proteins.

Three type K Bence-Jones proteins have been fully reduced and carboxymethylated with high-specific-activity iodo[(14)C]acetate. A tryptic digest and a chymotryptic digest of each protein were fractionated on a Sephadex column and the radioactive peptides were purified by paper electrophoresis. All the proteins studied had five unique carboxymethylated cysteine sequences. Three of these were identical with the exception of a single substitution, and two had some variations. The common peptides could be placed in the C-terminal half of the molecule. The variations around the other two half-cysteine residues provided information about the nature of the variability of the primary sequence of immunoglobulin kappa-chains. The results are consistent with the hypothesis that the chains derive from a common ancestor by somatic mutation of a small number of genes or by gene doubling and selection in the course of evolution. The isolation of the N-terminal peptide in methionine-containing Bence-Jones proteins is also described.

Amino Acid Sequence↗
PubMed2001

Identification of TSIX, encoding an RNA antisense to human XIST, reveals differences from its murine counterpart: implications for X inactivation.

X inactivation is the mammalian method for X-chromosome dosage compensation, but some features of this developmental process vary among mammals. Such species variations provide insights into the essential components of the pathway. Tsix encodes a transcript antisense to the murine Xist transcript and is expressed in the mouse embryo only during the initial stages of X inactivation; it has been shown to play a role in imprinted X inactivation in the mouse placenta. We have identified its counterpart within the human X inactivation center (XIC). Human TSIX produces a >30-kb transcript that is expressed only in cells of fetal origin; it is expressed from human XIC transgenes in mouse embryonic stem cells and from human embryoid-body-derived cells, but not from human adult somatic cells. Differences in the structure of human and murine genes indicate that human TSIX was truncated during evolution. These differences could explain the fact that X inactivation is not imprinted in human placenta, and they raise questions about the role of TSIX in random X inactivation.

Aging↗
PubMed2001

[Why do mutations cause disease--a protein chemical perspective].

BACKGROUND: Mutations are of fundamental importance for genetic diversity and evolution, but are also associated with diseases and death. Genetic polymorphisms are common even among healthy individuals and somatic mutations develop in large numbers throughout life. Although most mutations are classified as silent, others may be fatal. No universal procedures exist for the prediction of mutation phenotype. MATERIAL AND METHODS: As the main function of DNA is to code for proteins, it is logical to examine the impact of mutations on protein structure and function. On the basis of available databases and our own studies on mutations, protein structure and disease, we present a brief overview of their relationship. The phenylketonuria-associated mutations in human phenylalanine hydroxylase are discussed in more detail, as phenylketonuria is often considered a model system for other inherited metabolic diseases. RESULTS AND INTERPRETATION: We argue that studies of the kinetic and thermodynamic stability of proteins are important in order to understand the effects of many mutations, and we describe such studies. Knowledge about native, denatured and aggregated forms of proteins is essential to the understanding of how mutations can affect protein stability. We conclude that much of our knowledge in this area is still rudimentary, but we expect that this field of research will evolve rapidly over the next few years.

Amino Acid Sequence↗
PubMed1993

[The stomach speaks: chronicle of a deadly boredom].

The author describes the evolution of the psychotherapy of an 11 year old child: starting with an anonymous depression related to diffuse somatic complaints, it evolved into a playful assertion of a self which seems to depart from the family destiny. The author describes his counter-transferential feelings of tiredness and boredom which were compensated by a constant complicity with his young client. The author suggests that it is this very act of supporting the assertion and formulation of the subject, and disregarding unconditionally the boredom of what is said, which has brought about such a striking and sudden change.

Abdominal Pain↗
PubMed1998

The evolution of aging: a new approach to an old problem of biology.

Most gerontologists believe aging did not evolve, is accidental, and is unrelated to development. The opposite viewpoint is most likely correct. Genetic drift occurs in finite populations and leads to homozygosity in multiple-alleled traits. Episodic selection events will alter random drift towards homozygosity in alleles that increase fitness with respect to the selection event. Aging increases population turnover, which accelerates the benefit of genetic drift. This advantage of aging led to the evolution of aging systems (ASs). Periodic predation was the most prevalent episodic selection pressure in evolution. Effective defenses to predation that allow exceptionally long lifespans to evolve are shells, extreme intelligence, isolation, and flight. Without episodic predation, aging provides no advantage and aging systems will be deactivated to increase reproductive potential in unrestricted environments. The periodic advantage of aging led to the periodic evolution of aging systems. Newer aging systems co-opted and added to prior aging systems. Aging organisms should have one dominant, aging system that co-opts vestiges of earlier-evolved systems as well as vestiges of prior systems. In human evolution, aging systems chronologically emerged as follows: telomere shortening, mitochondrial aging, mutation accumulation, senescent gene expression (AS#4), targeted somatic tissue apoptotic-atrophy (AS#5), and female reproductive tissue apoptotic-atrophy (AS#6). During famine or drought, to avoid extinction, reproduction is curtailed and aging is slowed or somewhat reversed to postpone or reverse reproductive senescence. AS#4-AS#6 are gradual and reversible aging systems. The life-extending/rejuvenating effects of caloric restriction support the idea of aging reversibility. Development and aging are timed by the gradual loss of cytosine methylation in the genome. Methylated cytosines (5mC) inhibit gene transcription, and deoxyribonucleic acid (DNA) cleavage by restriction enzymes. Cleavage inhibition prevents apoptosis, which requires DNA fragmentation. Free radicals catalyze the demethylation of 5mC while antioxidants catalyze the remethylation of cytosine by altering the activity of DNA methyltransferases. Hormones act as either surrogate free radicals by stimulating the cyclic adenosine monophosphate (cAMP) pathway or as surrogate antioxidants through cyclic guanosine monophosphate (cGMP) pathway stimulation. Access to DNA containing 5mC inhibited developmental and aging genes and restriction sites is allowed by DNA helicase strand separation. Tightly wound DNA does not allow this access. The DNA helicase generates free radicals during strand separation; hormones either amplify or counteract this effect. Caloric restriction slows or reverses the aging process by increasing melatonin levels, which suppresses reproductive and free radical hormones, while increasing antioxidant hormone levels. Cell apoptosis during CR leads to somatic wasting and a release of DNA, which increases bioavailable cGMP. The rapid aging diseases of progeria, the three diseases: (xeroderma pigmentosum (XP), Cockayne syndrome(CS), and ataxia telangiectasia (AT)), and Werner's syndrome are related to or caused by defects in three separate DNA helicases. The rapid aging diseases caused by mitochondrial malfunctions mirror those seen in XP, CS, and AT. Comparing these diseases allows for assignment of the different symptoms of aging to their respective aging systems. Follicle-stimulating hormone (FSH) demethylates the genes of AS#4, luteinizing hormone (LH) of AS#5, and estrogen of AS#6 while cortisol may act cooperatively with FSH and LH, and 5-alpha dihydrotestosterone (DHT) with FSH in these role. The Werner's DNA helicase links timing of the age of puberty, menopause, and maximum lifespan in one mechanism. Telomerase is under hormonal control. Most cancers likely result from malfunctions in the programmed apoptosis of AS#5 and AS#6. The Hayflick limit is reached primarily through loss of cytosine methylation of genes that inhibit replication. Men suffer the diseases of AS#4 at a higher rate than women who suffer from AS#5 more often. Adult mammal cloning suggests aging-related cellular demethylation, and thus aging, is reversible. This theory suggests that the protective effect of smoking and ibuprofen for Alzheimer's disease is caused through LH suppression.

Aging↗
PubMed2003

Dramatic diversity of ciliate histone H4 genes revealed by comparisons of patterns of substitutions and paralog divergences among eukaryotes.

The accumulation of divergent histone H4 amino acid sequences within and between ciliate lineages challenges traditional views of the evolution of this essential eukaryotic protein. We analyzed histone H4 sequences from 13 species of ciliates and compared these data with sequences from well-sampled eukaryotic clades. Ciliate histone H4s differ from one another at as many as 46% of their amino acids, in contrast with the highly conserved character of this protein in most other eukaryotes. Equally striking, we find paralogs of histone H4 within ciliate genomes that differ by up to 25% of their amino acids, whereas paralogs in other eukaryotes share identical or nearly identical amino acid sequences. Moreover, the most divergent H4 proteins within ciliates are found in the lineages with highly processed macronuclear genomes. Our analyses demonstrate that the dual nature of ciliate genomes-the presence of a "germline" micronucleus and a "somatic" macronucleus within each cell-allowed the dramatic variation in ciliate histone genes by altering functional constraints or enabling adaptive evolution of the histone H4 protein, or both.

Amino Acid Substitution↗
PubMed2026

Antibody diversification in cartilaginous fishes: Mechanistic insights from the nurse shark and comparative perspectives across jawed vertebrates.

Antibody diversity in vertebrates arises through the coordinated actions of V(D)J recombination and somatic hypermutation (SHM). Cartilaginous fishes occupy a key phylogenetic position as the sister lineage to bony vertebrates and therefore provide important comparative insights into the evolution of adaptive immunity. This review focuses on the nurse shark (Ginglymostoma cirratum) as a representative model for examining antibody-diversification mechanisms in cartilaginous fishes. Shark immunoglobulin genes exhibit a multicluster organization, while immunoglobulin new antigen receptor (IgNAR), a heavy-chain-only isotype, contains a single variable domain with an extended complementarity-determining region 3 (CDR3) that can be stabilized by non-canonical disulfide bonds. These structural features, together with intracluster multi-D V(D)J recombination and distinctive SHM characterized by single and tandem substitutions and insertions/deletions, contribute to antibody diversification in sharks. By comparing cartilaginous fishes, ray-finned fishes, and mammals, this review highlights lineage-specific combinations of immunoglobulin gene organization, recombination, mutational processing, and affinity maturation. Within the heuristic framework proposed here, shark and mammalian systems are described as emphasizing "breadth-first" repertoire generation and "precision-first" affinity optimization, respectively. These terms indicate relative mechanistic emphases rather than mutually exclusive categories or sequential evolutionary stages, while ray-finned fishes exhibit a distinct combination of genomic organization and mutational features. Investigating antibody diversification in cartilaginous fishes not only advances our understanding of vertebrate immune evolution but also provides structural and mechanistic insights that may inform the development of engineered antibodies based on the IgNAR scaffold.

Antibody diversity↗
PubMed1996

The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family.

The three human lanosterol 14 alpha-demethylase (CYP51) genes have been mapped to human chromosomes 3, 7, and 13 using a polychromosomal somatic cell hybrid panel. Two of the genes have been cloned from human chromosome 3-specific (CYP51P1) or from human chromosome 13-containing (CYP51P2) cell hybrids. Both were found to be processed pseudogenes, the first reported in the cytochrome P450 (CYP) gene superfamily. The functional CYP51 gene resides on human chromosome 7. CYP51P1 is 96.5% identical to the human CYP51 coding sequence and is not interrupted with introns but has six in-frame stop codons resulting from point mutations. The intronless CYP51P2 gene is 97.2% identical to the CYP51 cDNA coding region. It has a 1-bp insertion leading to a change of reading frame after codon 9 and a stop codon after amino acid 81. In addition, the CYP51P2 sequence is interrupted with a 5' truncated 131-bp LINE-1 element after nucleotide 606. The element belongs to the youngest LINE subfamily Sb and is 98.2% identical to the LINE-1 element expressed in human teratocarcinoma cells. CYP51 processed pseudogenes are the only known examples of the reverse flow of genetic information during evolution of the large (more than 480 genes) CYP superfamily, suggesting expression in the germ line and a housekeeping function of the lanosterol 14 alpha-demethylase gene. CYP51 pseudogenes evolved by two independent reverse transcription events of the human CYP51 mRNA approximately 9.5 MYR (CYP51P2) and approximately 11.7 MYR (CYP51P1) ago and were inactivated soon after the insertion. The truncated L1 element was inserted into CYP51P2 approximately 6 MYR ago.

Amino Acid Sequence↗
PubMed2003

The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence.

Theories predict that the long-term survival of duplicated genes requires their functional diversification, which can be accomplished by either subfunctionalization (the partitioning of ancestral functions among duplicates) or neofunctionalization (the acquisition of novel function). Here, we characterize the CDY-related mammalian gene family, focusing on three aspects of its evolution: gene copy number, tissue expression profile and amino acid sequence. We show that the progenitor of this gene family arose de novo in the mammalian ancestor via domain accretion. This progenitor later duplicated to generate CDYL and CDYL2, two autosomal genes found in all extant mammals. Prior to human-mouse divergence (and perhaps preceding the eutherian radiation), a processed CDYL transcript retroposed onto the Y chromosome to create CDY, the Y-linked member of the family. In the simian lineage, CDY was retained and subsequently amplified on the Y. In non-simian mammals, however, CDY appears to have been lost. The retention of the Y-linked CDY genes in simians spurred the process of subfunctionalization and possibly neofunctionalization. Subfunctionalization is evidenced by the observation that simian CDYL and CDYL2 retained their somatic housekeeping transcripts but lost the spermatogenic transcripts to the newly arisen CDY. Neo-functionalization is suggested by the rapid evolution of the CDY protein sequence. Thus, the CDY-related family offers an instructive example of how duplicated genes undergo functional diversification in both expression profile and protein sequence. It also supports the previously postulated notion that there is a tendency for spermatogenic functions to transfer from autosomes to the Y chromosome.

Amino Acid Sequence↗
PubMed2000

Arabidopsis species hybrids in the study of species differences and evolution of amphiploidy in plants.

It is estimated that 5 million years of evolution separate Arabidopsis thaliana from its close relative Arabidopsis lyrata. The two taxa differ by many characteristics, and together they exemplify the differentiation of angiosperms into self-fertilizing and cross-fertilizing species as well as annual and perennial species. Despite their disparate life histories, the two species can be crossed to produce viable and vigorous hybrids exhibiting heterotic effects. Although pollen sterile, the hybrids produce viable ovules and were used as female parent in backcrosses to both parental species. The resulting backcross plants exhibited transgressive variation for a number of interesting developmental and growth traits as well as negative nuclear/cytoplasmic interactions. Moreover, the genesis of a fertile amphidiploid neospecies, apparently by spontaneous somatic doubling in an interspecific hybrid, was observed in the laboratory. The mechanisms responsible for the generation of amphiploids and the subsequent evolution of amphiploid genomes can now be studied through direct observation using the large arsenal of molecular tools available for Arabidopsis.

Arabidopsis↗
PubMed2000

The evolution of human skin coloration.

Skin color is one of the most conspicuous ways in which humans vary and has been widely used to define human races. Here we present new evidence indicating that variations in skin color are adaptive, and are related to the regulation of ultraviolet (UV) radiation penetration in the integument and its direct and indirect effects on fitness. Using remotely sensed data on UV radiation levels, hypotheses concerning the distribution of the skin colors of indigenous peoples relative to UV levels were tested quantitatively in this study for the first time. The major results of this study are: (1) skin reflectance is strongly correlated with absolute latitude and UV radiation levels. The highest correlation between skin reflectance and UV levels was observed at 545 nm, near the absorption maximum for oxyhemoglobin, suggesting that the main role of melanin pigmentation in humans is regulation of the effects of UV radiation on the contents of cutaneous blood vessels located in the dermis. (2) Predicted skin reflectances deviated little from observed values. (3) In all populations for which skin reflectance data were available for males and females, females were found to be lighter skinned than males. (4) The clinal gradation of skin coloration observed among indigenous peoples is correlated with UV radiation levels and represents a compromise solution to the conflicting physiological requirements of photoprotection and vitamin D synthesis. The earliest members of the hominid lineage probably had a mostly unpigmented or lightly pigmented integument covered with dark black hair, similar to that of the modern chimpanzee. The evolution of a naked, darkly pigmented integument occurred early in the evolution of the genus Homo. A dark epidermis protected sweat glands from UV-induced injury, thus insuring the integrity of somatic thermoregulation. Of greater significance to individual reproductive success was that highly melanized skin protected against UV-induced photolysis of folate (Branda & Eaton, 1978, Science201, 625-626; Jablonski, 1992, Proc. Australas. Soc. Hum. Biol.5, 455-462, 1999, Med. Hypotheses52, 581-582), a metabolite essential for normal development of the embryonic neural tube (Bower & Stanley, 1989, The Medical Journal of Australia150, 613-619; Medical Research Council Vitamin Research Group, 1991, The Lancet338, 31-37) and spermatogenesis (Cosentino et al., 1990, Proc. Natn. Acad. Sci. U.S.A.87, 1431-1435; Mathur et al., 1977, Fertility Sterility28, 1356-1360).As hominids migrated outside of the tropics, varying degrees of depigmentation evolved in order to permit UVB-induced synthesis of previtamin D(3). The lighter color of female skin may be required to permit synthesis of the relatively higher amounts of vitamin D(3)necessary during pregnancy and lactation. Skin coloration in humans is adaptive and labile. Skin pigmentation levels have changed more than once in human evolution. Because of this, skin coloration is of no value in determining phylogenetic relationships among modern human groups.

Adaptation, Physiological↗
PubMed2003

Thermodynamic and kinetic aspects of antibody evolution during the immune response to hapten.

We determined thermodynamic and kinetic parameters for the antigen-antibody interaction using a group of anti-(4-hydroxy-3-nitrophenyl)acetyl monoclonal antibodies whose differences in amino acid sequences had arisen only from somatic hypermutation. These monoclonal antibodies were considered to have originated from a common ancestor clone and to represent progression along the affinity maturation pathway. The kinetic measurements showed that both association and dissociation rate constants of the antigen-antibody interaction decreased during maturation. Thermodynamic measurements revealed that an increase in affinity was obtained by an increase in entropy without any significant change in enthalpy. These results suggested that the mechanism for the antigen-antibody interaction shifted from a "zipper" type to a "lock-and-key" type during antibody evolution.

Amino Acid Sequence↗
PubMed2001

Evolution of intrinsic growth and energy acquisition rates. I. Trade-offs with swimming performance in Menidia menidia.

Latitudinal populations of the Atlantic silverside, Menidia menidia, show substantial genetic variation in rates of energy acquistion and allocation. Reared in common environments, silversides from northern latitudes consume more food, grow faster and more efficiently, store more energy, and produce greater quantities of eggs than their southern conspecifics. The persistence of seemingly inferior southern genotypes in the face of ostensibly superior northern genotypes suggest that there are hidden evolutionary trade-offs associated with these elevated acquisition and allocation rates. We tested the hypothesis that rapid growth and high levels of food consumption trade-off against locomotory performance in M. menidia. We compared both aerobic (prolonged and endurance) and anaerobic (burst) swimming capacities between intrinsically fast-growing fish from the north (Nova Scotia, NS) and intrinsically slow-growing fish from the south (South Carolina, SC) and between growth-manipulated phenotypes within each population. We also compared swimming speeds and endurance between fasted and recently fed fish within populations. Maximum prolonged and burst swimming speeds of NS fish were significantly lower than those of SC fish, and swimming speeds of fast-growing phenotypes were lower than those of slow-growing phenotypes within populations. Fed fish had lower burst speeds and less endurance than fasted fish from the same population. Thus, high rates of growth and the consumption of large meals clearly diminish swimming performance, which likely increases vulnerability to predation and decreases survival and relative fitness. The submaximal growth rate of southern M. menidia appears to be adaptive, resulting from balancing selection on rates of somatic growth.

Aging↗
PubMed1978

A complete immunoglobulin gene is created by somatic recombination.

Using a pCRI plasmid containing an enzymatically synthesized, full-length DNA transcript of immunoglobulin lambda chain mRNA as the hybridization probe in the Southern gel blotting experiments (Southern, 1975), we identified three DNA fragments of 8.6, 4.8 and 3.5 kb in Eco RI-digested total DNA from BALB/c mouse embryos. A fourth fragment of 7.4 kb was found in addition to these three fragments in similarly digested total DNA from a lambda chain-secreting myeloma (HOPC 2020). We have cloned the four DNA fragments in an EK-2 phage vector, lambdaWES, and characterized them with respect to size, type of lambda gene sequences contained and position of these sequences in the fragments, using agarose gel electrophoresis, the gel blotting technique and electron microscopic R loop mapping. The embryonic DNA clones Ig 99 lambda, Ig 25lambda and Ig 13lambda contain one copy each of V lambdaI, C lambdaI and V lambdaII sequences, respectively, while the myeloma DNA clone Ig 303lambda contains one copy each of V lambdaI and C lambdaI sequences that are separated by a 1.2 kb nontranslated DNA segment. Ig 25lambda was also shown to contain a DNA segment of approximately 40 base pairs (bp) (J sequence) that lies 1.2 kb away from the C lambdaI sequence and is homologous to the V-C junction region of a lambdaI mRNA. Heteroduplex analysis of the three lambdaI DNA clones revealed that Ig 303lambda DNA is composed of two parts, one of which is entirely homologous to one end of Ig 99lambda, and the other to one end of Ig 25lambda DNA. The sequence arrangement observed in the cloned DNA is the same as that in the corresponding cellular DNA. This was shown by identifying certain restriction enzyme cleavage sites on the cloned DNAs and demonstrating the presence of these sites in the total cellular DNA by the gel blotting technique. The site of the homology switch is at the boundary of the V sequence and the 1.2 kb nontranslated DNA segment, and corresponds to the position of the J sequence on the Ig 25lambda DNA. We consider the above experimental results the most direct evidence for somatic rearrangement in immunoglobulin genes. We discuss the significance of these findings for the origin of genes in the evolution of higher organisms and in cell differentiation.

Animals↗
PubMed2005

Genetic and fluorescence studies of affinity maturation in related antibodies.

Affinity maturation, the process by which an organism's response to infection becomes more specific and more effective over time, occurs after somatic hypermutation of antibody genes in B-cells. This increase in affinity might be a result of the evolution of either specific interactions between antigen and antibody over time (enthalpic factors) or antibody binding site rigidification (entropic factors) or both. Here, monoclonal antibodies, derived from antibodies elicited at different points in the murine immune response after inoculation with the same diketone hapten, have been characterized both genetically and functionally. Though this hapten has previously been shown to produce the catalytic aldolase antibody 38C2, antibodies described here are not catalytic and unlike 38C2, form no covalent enzyme-substrate complex. Thus, they provide a system in which to assess contributions to the evolution of binding affinity. The genes for these non-catalytic antibodies have been sequenced and analyzed both with regard to their relationships to germ line genes, to each other, and to two commercially available catalytic aldolase antibodies. Consequences of particular mutations for antigen binding behavior are discussed. The protein products of these genes have been expressed, purified, and binding properties measured by two complementary techniques: the hapten-induced quenching of the native antibody fluorescence and the changes in the anisotropy of Prodan (6-propionyl-2-(dimethylamino)naphthalene), a fluorescent hapten analogue. Differences in binding affinity are related back to differences in the lengths and amino acid sequences of the complementary determining region 3 (CDR3) binding loop. Taken together with our earlier results on binding site heterogeneity from tryptophan lifetime analysis [Mohan, G.S., Chiu, P.T., Southern, C.A., O'Hara, P.B., 2004. Steady-state and multifrequency phase fluorometry studies of binding site flexibility in related antibodies. J. Phys. Chem. A 108, 7871-7877], affinity appears to be modulated by a combination of entropic and enthalpic factors, and not dominated by one or the other. Because these antibodies are not related to the same germ line gene, however, these results do not provide evidence for the dominance of enthalpy or entropy in evolving binding affinity in this system.

2-Naphthylamine↗