Caring for parents: an evolutionary rationale.

BACKGROUND: The evolutionary roots of human moral behavior are a key precondition to understanding human nature. Investigations usually start with a social dilemma and end up with a norm that can provide some insight into the origin of morality. We take the opposite direction by investigating whether the cultural norm that promotes helping parents and which is respected in different variants across cultures and is codified in several religions can spread through Darwinian competition. RESULTS: We show with a novel demographic model that the biological rule "During your reproductive period, give some of your resources to your post-fertile parents" will spread even if the cost of support given to post-fertile grandmothers considerably decreases the demographic parameters of fertile parents but radically increases the survival rate of grandchildren. The teaching of vital cultural content is likely to have been critical in making grandparental service valuable. We name this the Fifth Rule, after the Fifth Commandment that codifies such behaviors in Christianity. CONCLUSIONS: Selection for such behavior may have produced an innate moral tendency to honor parents even in situations, such as those experienced today, when the quantitative conditions would not necessarily favor the maintenance of this trait.

Comparable system-level organization of Archaea and Eukaryotes.

A central and long-standing issue in evolutionary theory is the origin of the biological variation upon which natural selection acts. Some hypotheses suggest that evolutionary change represents an adaptation to the surrounding environment within the constraints of an organism's innate characteristics. Elucidation of the origin and evolutionary relationship of species has been complemented by nucleotide sequence and gene content analyses, with profound implications for recognizing life's major domains. Understanding of evolutionary relationships may be further expanded by comparing systemic higher-level organization among species. Here we employ multivariate analyses to evaluate the biochemical reaction pathways characterizing 43 species. Comparison of the information transfer pathways of Archaea and Eukaryotes indicates a close relationship between these domains. In addition, whereas eukaryotic metabolic enzymes are primarily of bacterial origin, the pathway-level organization of archaeal and eukaryotic metabolic networks is more closely related. Our analyses therefore suggest that during the symbiotic evolution of eukaryotes, incorporation of bacterial metabolic enzymes into the proto-archaeal proteome was constrained by the host's pre-existing metabolic architecture.

The origin of the genetic code: amino acids as cofactors in an RNA world.

The genetic code, understood as the specific assignment of amino acids to nucleotide triplets, might have preceded the existence of translation. Amino acids became utilized as cofactors by ribozymes in a metabolically complex RNA world. Specific charging ribozymes linked amino acids to corresponding RNA handles, which could basepair with different ribozymes, via an anticodon hairpin, and so deliver the cofactor to the ribozyme. Growing of the 'handle' into a presumptive tRNA was possible while function was retained and modified throughout. A stereochemical relation between some amino acids and cognate anticodons/codons is likely to have been important in the earliest assignments. Recent experimental findings, including selection for ribozymes catalyzing peptide-bond formation and those utilizing an amino acid cofactor, hold promise that scenarios of this major transition can be tested.

Do deleterious mutations act synergistically? Metabolic control theory provides a partial answer.

Metabolic control theory is used to derive conditions under which two deleterious mutations affecting the dynamics of a metabolic pathway act synergistically. It is found that two mutations tend to act mostly synergistically when they reduce the activity of the same enzyme. If the two mutations affect different enzymes, the conclusion depends on the way that fitness is determined by aspects of the pathway. The cases analyzed are: selection for (1) maximal flux, (2) maximal equilibrium concentration (pool size) of an intermediate, (3) optimal flux, (4) optimal pool size. The respective types of epistasis found are: (1) antagonistic, (2) partly synergistic, (3-4) synergism is likely to predominate over antagonism. This results in somewhat different predictions concerning the effect of metabolic mutations on fitness in prokaryotes and eukaryotes. The fact that bacteria are largely clonal but have often a mosaic gene structure is consistent with expectations from the model.

Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations.

Mitochondrial DNAs (mtDNAs) from 167 American Indians including 87 Amerind-speakers (Amerinds) and 80 Nadene-speakers (Nadene) were surveyed for sequence variation by detailed restriction analysis. All Native American mtDNAs clustered into one of four distinct lineages, defined by the restriction site variants: HincII site loss at np 13,259, AluI site loss at np 5,176, 9-base pair (9-bp) COII-tRNA(Lys) intergenic deletion and HaeIII site gain at np 663. The HincII np 13,259 and AluI np 5,176 lineages were observed exclusively in Amerinds and were shared by all such tribal groups analyzed, thus demonstrating that North, Central and South American Amerinds originated from a common ancestral genetic stock. The 9-bp deletion and HaeIII np 663 lineages were found in both the Amerinds and Nadene but the Nadene HaeIII np 663 lineage had a unique sublineage defined by an RsaI site loss at np 16,329. The amount of sequence variation accumulated in the Amerind HincII np 13,259 and AluI np 5,176 lineages and that in the Amerind portion of the HaeIII np 663 lineage all gave divergence times in the order of 20,000 years before present. The divergence time for the Nadene portion of the HaeIII np 663 lineage was about 6,000-10,000 years. Hence, the ancestral Nadene migrated from Asia independently and considerably more recently than the progenitors of the Amerinds. The divergence times of both the Amerind and Nadene branches of the COII-tRNA(Lys) deletion lineage were intermediate between the Amerind and Nadene specific lineages, raising the possibility of a third source of mtDNA in American Indians.

Four letters in the genetic alphabet: a frozen evolutionary optimum?

Piccirilli et al. (Nature, Lond. 343, 33-37 (1990)) have shown experimentally that the replicatable introduction of new base pairs into the genetic alphabet is chemically feasible. The fact that our current genetic alphabet uses only two base pairs can be explained provided that this basic feature of organisms became fixed in an RNA world utilizing ribozymes rather than protein enzymes. The fitness of such ribo-organisms is determined by two factors: replication fidelity and overall catalytic efficiency (basic metabolic or growth rate). Replication fidelity is shown to decrease roughly exponentially, and catalytic efficiency is shown to increase with diminishing returns, with the number of letters for a fixed genome length; hence their product, i.e. fitness, gives rise to a set of values with an optimum. Under a wide range of parameter values the optimum rests at two base pairs. The chemical identity of the particular choice in our genetic alphabet can also be rationalized. This optimum is considered frozen, as currently the dominant catalysts are proteins rather than RNAs.

A classification of replicators and lambda-calculus models of biological organization.

W. Fontana & L.W. Buss (Proc. Natn. Acad. Sci. U.S.A. 91, 757 (1994) and Bull. math. Biol. 56, 1 (1994) have put forward a scheme for a theory of biological organization based on the lambda-calculus. Their key innovation was to represent, with the aid of this calculus, a certain minimal chemistry. Although this idea is very promising, their concrete formulation could be improved if suggestions for the following items were incorporated: (i) a better coding of chemical reactions; (ii) a reinterpretation of the evolutionary behaviour of autocatalytic chemical networks; (iii) a better appreciation of morphological and genetic factors; (iv) a more complete embedding of the theory into the background of relevant earlier contributions. Confusion can be stopped by the application of a proper classification of replicators (important categories being: processive and modular, limited and unlimited hereditary replicators). Suggestions to facilitate improvement are made explicit in this paper. The most challenging task would be to model the transition from processive, limited hereditary replicators to modular replicators with limited and unlimited heredity.

Prevalence of diagnosed diabetes in circumpolar indigenous populations.

The prevalence of diagnosed diabetes in several genetically closely related indigenous populations in the circumpolar arctic and subarctic regions of Russia, Alaska and Canada is compared. The age-standardized (to the IARC's hypothetical world population) prevalence ranged from 1.8/1000 among the Chukchi and Eskimo of Chukotka, 3.6 and 7.9/1000 among the Eskimos/Inuit of the Canadian Northwest Territories (NWT) and Alaska respectively, 7.1, 9.3 and 18.6/1000 among Athapaskan Indians in the NWT, Yukon and Alaska respectively, to a high of 22.7/1000 among the Aleuts in Alaska. All are below the US all-race prevalence of 23.5/1000 and far below the extreme high prevalence reported from many North American Indian tribes. As a group, such arctic and subarctic peoples have a much shorter and less intense history of European contact and acculturation. Environmental factors are also likely to be responsible for the current differences between these indigenous populations in the circumpolar region, assuming that they share susceptibility genes for diabetes inferred from their close genetic relationships based on markers in other loci. Formal surveys of glucose tolerance and potential risk factors such as diet, physical activity, obesity, insulin resistance and genetic admixture in the circumpolar region would improve knowledge of the aetiology of diabetes in genetically and culturally diverse human populations.

Dietary change and plasma glucose levels in an Amerindian population undergoing cultural transition.

Dietary change among adult Dogrib Indians of the Northwest Territories, Canada, is examined in conjunction with differences in mean glucose levels among more acculturated-less acculturated settlements. There are significant differences in the intake components derived from non-traditional foods by community and by age. However, the traditional food base is stable. This pattern suggests that dietary acculturation may initially consist of the addition of new foods to a stable traditional dietary, rather than replacement of traditional foods. The net effect is an increase in caloric intake. Age-sex-adjusted plasma glucose levels among four Dogrib settlements did not differ significantly. Comparison of participants who had been tested in a 1979 investigation of glucose tolerance showed that the current lack of intervillage differences can be attributed to an unexplained decrease of mean plasma glucose in the most acculturated village. Either dietary shift does not influence glucose levels, or, its effect can be detected only in conjunction with some other environmental factor. Among the Dogrib, acculturation-associated dietary changes are clearly present. However, their role in influencing plasma glucose levels still needs to be demonstrated.

Geographical distribution of diabetes among the native population of Canada: a national survey.

The prevalence of diagnosed diabetes was determined for 76% of the registered Indian and Inuit (Eskimo) population of Canada from case registers maintained by the federal agency responsible for Indian health services. A total of 5324 cases were ascertained. The age-sex adjusted rate varied among the Indians from a low of 0.8% in the Northwest Territories to a high of 8.7% in the Atlantic region. Among Inuit, the prevalence was 0.4%. Most cases occur in middle-aged or older individuals, with a higher prevalence among Indian (but not Inuit) females. An ecologic analysis was performed with the crude prevalence of individual communities regressed upon independent variables that included longitude, latitude, geographic isolation, culture area, and language family. Stepwise regressions were also carried out within the Algonkian, Athapaskan, and Eskimoan language families. For the national sample, composite language phylum-culture area predictors were used. The results in the national sample confirmed most findings in the individual language family analysis. Six predictors: latitude, Northeast-Algonkian, Northeast-Iroquoian, Subarctic-Algonkian, Plains-Siouan, and Plains-Algonkian, ranked here in decreasing order of importance, explained 48.4% of the variation in diabetes prevalence. All the named groups had rates significantly greater than found in the reference group of Arctic-Eskimoans. We conclude that the distribution of diabetes among Canadian natives is determined by both genetic and environmental factors.

Early evolution of microtubules and undulipodia.

A critique of both autogeneous and symbiotic hypotheses for the origin of microtubules and cilia and eukaryotic flagella (undulipodia) is presented. It is proposed that spirochetes provided the ancient eukaryotic cell with microtubules twice; cytoplasmic microtubules originated from phagocytosed spirochetes whereas axopodial tubules of undulipodia were transformed from ectosymbiotic spirochetes. A role in transport for microtubules in spirochetes together with a detailed scenario by which free-living spirochetes attached as ectosymbionts and subsequently differentiated into undulipodia is outlined. A mechanism for the continuity of motility in the form of "training" of the novel microtubular axoneme by the ancient spirochete motility apparatus is proposed. Transitional states (missing links) are unlikely to have survived. Constraints regarding the nature of the host cell are discussed. A corresponding flowchart of the early evolution of eukaryotes is presented in which plastids and mitochondria are polyphyletic in their origins.

The impact of low carbohydrate consumption on glucose tolerance, insulin concentration and insulin response to glucose challenge in Dogrib Indians.

The NDDG and the WHO recommend that individuals undergoing an oral glucose tolerance test (OGTT) consume a minimum of 150 gm of carbohydrate on each of three days preceding the OGTT. Carbohydrate restriction affects the diagnostic accuracy of the OGTT. This is a problem for the diagnosis of diabetes among northern peoples, but may also have relevance for other Amerindians. Dogrib Indians of the Canadian NWT still rely on the traditional dietary, based on caribou-hunting and fishing. The impact of low carbohydrate consumption on oral glucose tolerance, insulin concentration (IC), and insulin response (IR) to oral glucose challenge can thus be examined in this population. Carbohydrate Intake (CI) on the day preceding the OGTT was assessed by a 24-hour dietary recall, and was correlated with another indicator of dietary intake, consumption on "a usual winter day." CI was categorized three ways, and two ways (less than 150 gm; greater than or equal to 150 gm). Covariance analysis of the best indicator of glucose tolerance, the hour-2 plasma glucose concentration, found that there were no differences in glucose levels among the consumers of different amounts of carbohydrate. Regression analysis showed that in the Dogrib fasting insulin (FI) is the best predictor of total IC, measured as insulin area. The impact of CI on FI, total IC and IR to a glucose load was assessed. The only significant effect was on FI in the total sample. Among normoglycemics (hr-2 glucose less than 11.1 mmol/L) no effect was seen. IC and IR were not influenced by the previous day's CI in either the total or normoglycemic samples. Nevertheless, the pattern of IR, including normal basal insulin levels with hour-1 IR 10 times higher than baseline occur in all Dogrib. This response pattern is normal for Dogrib, and should not be seen as a portender of glucose intolerance in them.

What is the optimum size for the genetic alphabet?

An important question in biology is why the genetic alphabet is made of just two base pairs (G.C and A.T). This is particularly interesting because of the recent demonstration [Piccirilli, J. A., Krauch, T., Moroney, S. E. & Benner, S. A. (1990) Nature (London) 343, 33-37] that the alphabet can in principle be larger. It is possible to explain the size of the present genetic alphabet as a frozen character state that was an evolutionary optimum in an RNA world when nucleic acids functioned both for storing genetic information and for expressing information as enzymatically active RNA molecules--i.e., ribozymes. A previous model [Szathmáry, E. (1991) Proc. R. Soc. London Ser. B 245, 91-99] has described the principle of this approach. The present paper confirms and extends these results by showing explicitly the ways in which copying fidelity and metabolic efficiency change with the size of the genetic alphabet.

Viral sex, levels of selection, and the origin of life.

Several issues in Chao's related paper J. theor. Biol. (1991, 153, 229-246) are revisited. It is argued that mixes of segments from different viral coinfection groups cannot be regarded as sex, unless one is willing to accept that these groups are replicators and individuals. But, because selection in coinfection groups is dynamically analogous to that in trait groups in structured demes, one should also regard these latter groups as replicators. This approach is unacceptable since the groups in question have irregular ploidies, an unfixed number of parents, and no rules analogous to those of meiosis. It is emphasized, however, that the effective presence of neighbour-modulated fitness can ensure dynamical coexistence of covirus segments, even if the equal net reproduction rate within groups is not warranted. It seems that during the origin of coviruses from complete viruses, a higher-level evolutionary unit has become disintegrated, whereas during the origin of life a higher-level unit, the protocell, has emerged from lower-level ones, i.e. unlinked, replicating genes. These two gene-level systems are not homologous, but analogous. Although it is true that the resistance to parasites and the need to avoid a mutational collapse of the genome are likely to have called for some compartmentation in precellular stages of evolution, no clear demonstration, that the proposed mechanisms (the compartmentalized hypercycle and the stochastic corrector model) do in fact solve the error threshold problem, exists. Neither has a plausible mode of protocellular sex been suggested.

Natural selection and dynamical coexistence of defective and complementing virus segments.

Defective interfering (DI) particles are known to coexist with wildtype viruses under high multiplicity of infection. The complementing segments of coviruses (multiparticle, segmented viruses) coexist under similar conditions. In all cases, within-cell reproductive advantage to one of the segments is rather common. This fact, and the observation that DI particles are parasites, whereas covirus segments are mutualists, call for a non-trivial model of stable dynamical coexistence. The methodical novelty is the application of the structured deme model to virus dynamics. It assumes that biochemical ("ecological") interactions occur among segments within a coinfection group, established through random infection of the cells, and there is complete mixing of the various types emerging from all the coinfection groups (cells) in the virus pool between two infections. Through the application of the model, analytic results on the coexistence of virus segments are obtained for the following cases: virus-DI particle, virus-DI particle-resistant virus, covirus pair, virus-covirus.