Teleconsulta médica. Análisis y recomendaciones del Departamento de Ética del Colegio Médico de Chile

The possibility of allowing patients access to health professionals, has been greatly facilitated by advances in technology. Indeed, nowadays it is possible not only direct contact between one health professional with another, but also the possibility of sending images and other tests to consult distant colleagues. This has undoubtedly enabled better health care for many patients. It is also possible for a patient to consult a doctor directly in a remote and synchronous way with oral and visual contact, thus establishing a new form of medical consultation. It is this last way of relationship, which has already spread as a practice in normal times, which arouses apprehensions about the ethical requirements that a consultation must meet. This work by the Ethics Department of the Chilean Medical Association seeks to reflect on the ethical demands of a medical consultation and on the shortcomings that teleconsultation has. It also aims to propose several recommendations, so that this new form of doctor-patient relationship serves as a complement to traditional care, without jeopardizing the objectives of a medical action.

Argumentos éticos a favor y en contra de la participación del profesional médico en la muerte asistida. Análisis del Departamento de Ética del Colegio Médico de Chile / Ethical arguments for and against the participation of the medical profession in assisted death: analysis of the Ethics Department of the Chilean Medical Association

The discussion of a bill that allows medically assisted death (MAD) in Chile, revived the debate about the ethics of this practice. The Department of Ethics of the Chilean Medical Association herein analyzes arguments in favor or against the participation of the medical profession in MAD. Among the main arguments against the participation of physicians in this practice are that MAD conflicts with the basic ethical principles of medical practice, that it is contrary to the purposes of medicine and that it could erode the patients' and society's confidence in physicians. The arguments in favor are related to physician´s compassion and non-abandonment of patients during their illness, choosing palliative care and ushering them to the final instance. Additionally, there is social expectation that this practice will be carried out by trained physicians who can verify that the strict criteria established by the legislation are met, guarantee that it obeys to a repeated request of a fully capable patient, and who is able to deal with the complications of the procedure. In this document we aimed to represent the different perspectives about physicians' participation in MAD, offering arguments to colleagues and stimulating their participation in this important debate.

Development of a small panel of SNPs to infer ancestry in Chileans that distinguishes Aymara and Mapuche components

BACKGROUND: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socio-economic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. RESULTS: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors. CONCLUSIONS: We have conducted the most extensive sampling, across many different cities, of current Chilean population. Ancestry varied significantly by latitude and human development. The panel of AIMs is available to the community for estimating ancestry at low cost in Chileans and other populations with similar ancestry.

Aspectos éticos de la conducta del médico ante personas en huelga de hambre: opinión del Departamento de Ética del Colegio Médico de Chile / Ethical aspects of the doctors' behavior towards people on hunger strike: position paper from the Ethics Department of the Chilean Medical Association

Every so often, in Chile there is a discussion about the role of physicians in the care of people on hunger strike (HS). In this document, we review the ethical aspects of health care for persons in HS, aiming to provide guidelines to medical doctors who are required to attend them. First, we make an important distinction between HS and suicide, since the former is used as a protest and denunciation tool, while suicide seeks deliberately to end a life. Then we describe the three roles that the health professional can fulfill: as a treating doctor, as an expert or as an official of a prison. The respect for the autonomy and dignity of the person in HS must prevail whatever the role of the physician. Therefore, we maintain that under no circumstances, people who have autonomously decided to be in HS should be fed by force. Due to the complexity of the issue, we make special considerations about the management of minors and the non-competent persons in HS. In conclusion, we adhere to the principles that inspire the Declaration of Malta, which indicate that it would be preferable to "allow a person on hunger strike to die in dignity, rather than subjecting them to repeated interventions against their will".

Selective intra-dinucleotide interactions and periodicities of bases separated by K sites: a new vision and tool for phylogeny analyses

Direct tests of the random or non-random distribution of nucleotides on genomes have been devised to test the hypothesis of neutral, nearly-neutral or selective evolution. These tests are based on the direct base distribution and are independent of the functional (coding or non-coding) or structural (repeated or unique sequences) properties of the DNA. The first approach described the longitudinal distribution of bases in tandem repeats under the Bose-Einstein statistics. A huge deviation from randomness was found. A second approach was the study of the base distribution within dinucleotides whose bases were separated by 0, 1, 2... K nucleotides. Again an enormous difference from the random distribution was found with significances out of tables and programs. These test values were periodical and included the 16 dinucleotides. For example a high ¨positive¨ (more observed than expected dinucleotides) value, found in dinucleotides whose bases were separated by (3K + 2) sites, was preceded by two smaller ¨negative¨ (less observed than expected dinucleotides) values, whose bases were separated by (3K) or (3K + 1) sites. We examined mtDNAs, prokaryote genomes and some eukaryote chromosomes and found that the significant non-random interactions and periodicities were present up to 1000 or more sites of base separation and in human chromosome 21 until separations of more than 10 millions sites. Each nucleotide has its own significant value of its distance to neutrality; this yields 16 hierarchical significances. A three dimensional table with the number of sites of separation between the bases and the 16 significances (the third dimension is the dinucleotide, individual or taxon involved) gives directly an evolutionary state of the analyzed genome that can be used to obtain phylogenies. An example is provided.

Aproximación ética científica al doble efecto o único bien posible en el aborto terapéutico / Scientific ethical approach to double effect or only possible good in therapeutic abortion / Aproximação ética científica ao duplo efeito ou único bem possível no aborto terapêutico

El estudio muestra como la doctrina o principio del doble efecto (DDE) de una acción con efecto secundario negativo no puede aplicarse a todos los casos de aborto terapéutico (AT). Con el análisis de las causas e indicación de AT se demuestra que solo algunos de estos corresponden a DDE. Cuando no es el feto el que lleva a la madre a tener un embarazo de alto riesgo con amenaza de daño severo o muerte para ella, el caso puede adscribirse a la DDE; cuando es el feto directa o indirectamente el que causa a lleva a ese riesgo materno, el caso no se adscribe a la DDE. Si el feto es la causa de la muerte inminente de la madre, la remoción de la causa, que es la terapia adecuada, coincide con matarlo; entonces la acción buena (salvar a la madre tratándola causalmente) es la misma que la mala (matar al feto), situación que no puede asimilarse sea a la DDE o a la doctrina del mal menor. Más aún, decidir no interrumpir el embarazo produciría la muerte de la madre y el feto. El caso debería adscribirse al principio del único bien posible.

This study shows the inapplicability of the doctrine of double effect (DDE) to all the cases of therapeutic abortion (TA). The causes of the maternal risk define cases that cannot be included in the DDE. When it is not the embryo or fetus that produces the mother pathology the case can be assigned to the DDE. When the embryo or fetus produces directly or indirectly the process that threatens the mother’s life the case cannot be assigned to the DDE. If the fetus is the cause of the imminent mother’s death, the removal of the cause, that is the proper therapy, coincides with killing him or her; then the good action (to save therapeutically the mother) is the same to the bad action (to kill the fetus) and this situation cannot be assimilated either to the DDE or to the doctrine of the lesser evil. Deciding not to kill the fetus will produce the death of the mother and the fetus. So this situation should be ascribed to the principle of the unique possible well.

O estudo mostra como a doutrina ou princípio do duplo efeito (DDE) de uma ação com efeito secundário negativo não pode aplicar-se a todos os casos de aborto terapêutico (AT). Com a análise das causas e indicação de AT se demonstra que só alguns destes correspondem a DDE. Quando não é o feto que leva a mãe a ter uma gravidez de alto risco com ameaça de dano severo ou morte para ela, o caso pode circunscrever-se à DDE; quando é o feto direta ou indiretamente quem causa ou leva a esse risco materno, o caso não se circunscreve a DDE. Se o feto é a causa da morte iminente da mãe, a remoção da causa, que é a terapia adequada, coincide em matá-lo; então a ação boa (salvar a mãe tratando-a causalmente) é a mesma que a má (matar o feto), situação que não pode assimilar-se à DDE ou à doutrina do mal menor. Mais ainda, decidir não interromper a gravidez produziria a morte da mãe e do feto. O caso deveria circunscrever-se ao princípio do único bem possível.

El médico y la objeción de conciencia: opinión del Departamento de Ética del Colegio Médico de Chile A. G. / Position paper from the Department of Ethics of the Chilean College of Physicians about conscientious objection

The Chilean bill that regulates abortion for three cases (Bulletin Nº 9895-11) includes the possibility that health professionals may manifest their conscientious objection (CO) to perform this procedure. Due to the broad impact that the issue of C O had, the Ethics Department of the Chilean College of Physicians considered important to review this concept and its ethical and legal basis, especially in the field of sexual and reproductive health. In the present document, we define the practical limit s of CO, both for the proper fulfillment of the medical profession obligations, and for the due respect and non-discrimination that the professional objector deserves. We analyze the denial of some health institutions to perform abortions if it is legalize d, and we end with recommendations adjusted to the Chilean reality. Specifically, we recognize the right to conscientious objection that all physicians who directly participate in a professional act have. But we a lso recognize that physicians have ineludib le obligations towards their patients, including the obligation to inform about the existence of this service, how to access to it and -as set out in our code of ethics- to ensure that another colleague will continue attending the patient.

The structure of selective dinucleotide interactions and periodicities in D melanogaster mtDNA

BACKGROUND: We found a strong selective 3-sites periodicity of deviations from randomness of the dinucleotide (DN) distribution, where both bases of DN were separated by 1, 2, K sites in prokaryotes and mtDNA. Three main aspects are studied. I) the specific 3 K-sites periodic structure of the 16 DN. II) to discard the possibility that the periodicity was produced by the highly nonrandom interactive association of contiguous bases, by studying the interaction of non-contiguous bases, the first one chosen each I sites and the second chosen J sites downstream. III) the difference between this selective periodicity of association (distance to randomness) of the four bases with the described fixed periodicities of base sequences. RESULTS: I) The 16 pairs presented a consistent periodicity in the strength of association of both bases of the pairs; the most deviated pairs are those where G and C are involved and the least deviated ones are those where A and T are involved. II) we found significant non-random interactions when the first nucleotide is chosen every I sites and the second J sites downstream until I=J=76. III) we showed conclusive differences between these internucleotide association periodicities and sequence periodicities. CONCLUSIONS: This relational selective periodicity is different from sequence periodicities and indicates that any base strongly interacts with the bases of the residual genome; this interaction and periodicity is highly structured and systematic for every pair of bases. This interaction should be destroyed in few generations by recurrent mutation; it is only compatible with the Synthetic Theory of Evolution and agrees with the Wright's adaptive landscape conception and evolution by shifting balanced adaptive peaks.

Malignant melanoma in Chile: different site distribution between private and state patients

BACKGROUND: The body site location of primary Malignant Melanoma (MM) has been correlated with prognosis and survival. Ethnic, genetics, sun exposure factors are related to the anatomical distribution of MM. Low and high socioeconomic strata in Chile differ in ethnic, genetic and cultural conditions. The purpose of this study was to analyze the anatomical MM distribution in the Chilean population in both strata searching for differences due to their ethno-genetic-cultural differences. Records of 1148 MM, 575cases from state hospitals (Low Socioeconomic Strata, LSS) and 573 cases from private clinics (High Socioeconomic Strata, HSS) were analyzed by body site. RESULTS: Females from LSS showed a higher number of MM in soles, cheeks, and around the eye area. Females from the HSS showed a higher number of MM in dorsal feet and dorsal hands. Males from LSS showed a higher number of MM in soles, around the eye area, and cheeks. However, males from HSS showed a higher number of MM in the trunk, and in the arms. Acral MM was significantly higher in LSS than in the HSS in both sexes. The Chilean population from the HSS and LSS showed differences in the distribution of MM by site. Furthermore, gender differences in the proportion of MM analyzed by anatomical site are observed in both strata. CONCLUSIONS: Results show evidence that differential genetics factors, sun exposure, or other environmental or cultural factors of both strata may account for these differences.

The monthly rhythm of incidence and age at menarche: thirty five years of research: The circa-vacation-study expectancy rhythm of incidence and age at menarche

The hypothesis that the vacation-study-expectancy scholar regime produces most of the monthly rhythm of the age at menarche (AaM) was tested. Studies on monthly menarche incidence (MI) refuted climatic factors as a main factor in this rhythm, and indicated that the main factor of this rhythm is the succession of expectancies of study (Stu-months) or vacation (Vac-months) months within a year. Thus the hypothesis of seasonal circa-annual rhythm should be modified to the circa-[vacation (fiesta)]-[study (non-fiesta)]-expectancies rhythm for the MI and age at menarche annual rhythms. In several countries Vac-months had higher MI than Stu-months. The high MI of Vac-months was followed by a large decrease when girls started their studies and a MI increase occurred as vacations approached. The hypothesis proposes that at the end of vacations and at the beginning of the study period the AaM should be lowest, and then the mean of AaM should increase because of the menarche delay of girls whose menarche was arrested by the initiation of school work. This pattern was found in four independent samples, from Chile, Colombia, USA and Brazil. The probability that this result be due to random fluctuation of means is extraordinarily low (P<10-8). I conclude that the influence of the expectancy of vacation and study periods on the monthly rhythm of the age at menarche is a real process that accounts for most of this rhythm.

Foundational errors in the Neutral and Nearly-Neutral theories of evolution in relation to the Synthetic Theory: Is a new evolutionary paradigm necessary?

The Neutral Theory of Evolution (NTE) proposes mutation and random genetic drift as the most important evolutionary factors. The most conspicuous feature of evolution is the genomic stability during paleontological eras and lack of variation among taxa; 98% or more of nucleotide sites are monomorphic within a species. NTE explains this homology by random fixation of neutral bases and negative selection (purifying selection) that does not contribute either to evolution or polymorphisms. Purifying selection is insufficient to account for this evolutionary feature and the Nearly-Neutral Theory of Evolution (N-NTE) included negative selection with coefficients as low as mutation rate. These NTE and N-NTE propositions are thermodynamically (tendency to random distributions, second law), biotically (recurrent mutation), logically and mathematically (resilient equilibria instead of fixation by drift) untenable. Recurrent forward and backward mutation and random fluctuations of base frequencies alone in a site make life organization and fixations impossible. Drift is not a directional evolutionary factor, but a directional tendency of matter-energy processes (second law) which threatens the biotic organization. Drift cannot drive evolution. In a site, the mutation rates among bases and selection coefficients determine the resilient equilibrium frequency of bases that genetic drift cannot change. The expected neutral random interaction among nucleotides is zero; however, huge interactions and periodicities were found between bases of dinucleotides separated by 1, 2... and more than 1,000 sites. Every base is co-adapted with the whole genome. Neutralists found that neutral evolution is independent of population size (N); thus neutral evolution should be independent of drift, because drift effect is dependent upon N. Also, chromosome size and shape as well as protein size are far from random.

Response of the G2-prophase checkpoint to genotoxic drugs in lymphocytes from healthy individuals

We analyzed the in vitro effects of the anti-tumoral drugs doxorubicin, cytosine arabinoside and hydroxyurea on the G2-prophase checkpoint in lymphocytes from healthy individuals. At biologically equivalent concentrations, the induced DNA damage activated the corresponding checkpoint. Thus: i) there was a concentration-dependent delay of G2 time and an increase of both the total DNA lesions produced and repaired before metaphase and; ii) G2-checkpoint adaptation took place as chromosome aberrations (CAs) started to appear in the metaphase, indicating the presence of unrepaired double-strand breaks (DSBs) in the previous G2. The checkpoint ATM/ATR kinases are involved in DSB repair, since the recorded frequency of CAs increased when both kinases were caffeine-abrogated. In genotoxic-treated cells about three-fold higher repair activity was observed in relation to the endogenous background level of DNA lesions. The maximum rate of DNA repaired was 3.4 CAs/100 metaphases/hour, this rise being accompanied by a modest 1.3 fold lengthening of late G2 prophase timing. Because of mitotic chromosome condensation, no DSBs repair can take place until the G1 phase of the next cell cycle, when it occurs by DNA non-homologous end joining (NHEJ). Chromosomal rearrangements formed as a consequence of these error-prone DSB repairs ensure the development of genome instability through the DNA-fusion-bridge cycle. Hence, adaptation of the G2 checkpoint supports the appearance of secondary neoplasia in patients pretreated with genotoxic drugs.

Ética científica del aborto en caso de anencefalia / Scientific ethics of the abortion with anencephalic fetus

author proposes, from the perspective of the Scientific Ethics, to assimilate anencephalic fetuses to non-human fetuses because they have a large deficiency of the brain that is the organ for human specificity. This proposal comes after considering arguments and facts from ontogeny, phylogeny, from the situation of loss of the brain in the adult life and from the organic specificity of the human condition given by the brain. If anencephalic fetuses are not human, the interruption of their pregnancy cannot be considered as abortion, regardless the pregnancy stage.

Colonización de la cavidad oral por Streptococcus grupo mutans, según edad, evaluado en saliva por un método semi-cuantitativo / Colonization of the oral cavity by group mutans streptococci according to age assesed by a semi-quantitative method in saliva

Objective: To evaluate the colonization of group mutans streptococci according to age, measuring the amount of bacteria in saliva with a semi-quantitative method in a population attended in public and private dental centers of the Metropolitan Region, Santiago, Chile. Patients and Methods: Saliva samples were obtained from 14,649 patients aged 5 to 40 years, in one public and 5 private dental centers. Bacteria concentration was estimated by the comparison with a standard counting-chart. The concentration of group mutans streptococci in saliva was test by a 3-way ANOVA. Results: Bacterial concentration of Streptococcus mutans related with the age of patients was significant (p < 0.001). Bacterial concentration in the preschool age was 4,7 x 10(5) CFU/mL at 5 years, while 6,0 x10(5) CFU/mL at 12 years of age, with a decrease in patients over 30 years. Bacterial concentration was significantly different in the six centers of the study. Conclusions: The semi-quantitative method was useful to determine the colonization by Streptococcus mutans according to age. This could help for identifying population at high risk of dental caries and to develop oral health prevention programs in specific populations.

Objetivo: Evaluar el nivel de colonización Streptococcus grupo mutans según la edad, midiendo en saliva, con un método semi-cuantitativo, la cantidad de bacterias presente en una población que acude a centros odontológicos públicos y privados de la Región Metropolitana de Chile. Pacientes y Métodos: Se obtuvieron de 14.649 muestras de saliva de pacientes incluyendo hombres y mujeres, de 5 a 40 años, en un centro de atención estatal y en cinco de atención privada. El método de recuento fue la comparación con una tabla normada de concentraciones. El análisis estadístico incluyó ANOVA. Resultados: Se encontró que el recuento de Streptococcus grupo mutans en relación a las edades de los pacientes fue significativo (p < 0,001). El recuento de bacterias en los preescolares de 5 años fue alrededor de 4.7x10(5) ufc/ mL de saliva mientras que en los niños de 12 años fue de 6.0x10(5) ufc/mL, observándose además una disminución de la carga bacteriana en los pacientes de 30 años. A edades superiores se apreció un descenso paulatino. La concentración bacteriana fue significativamente distinta en los seis centros estudiados. Conclusiones: Este método de recuento de colonias a través de la espátula permitió determinar el grado de colonización producida por Steptococcus grupo mutans según las edades, es de utilidad para identificar la población de alto riesgo de caries dentales y su aplicación ayudaría a desarrollar programas de prevención en salud oral en poblaciones especificas.

Human Sociogenetics

In three cities of Chile (Santiago, Valparaiso, Valdivia) the A allele and phenotype (ABO blood group) are more frequent in the higher socioeconomic strata (SES) and the O allele and phenotype are in the lower ones. This constitutes a structured sociogenetic cline (SGC). The B allele and phenotypes (B+AB) present a rather erratic or contradictory distribution among SES. This SGC was also found in England. The standard interpretation of the origin and maintenance of this SGC in Chile is founded on socio-ethno-historic-cultural and drift factors followed by socioeconomic assortative mating that has occurred since the origin of Chileans by the admixture of Europeans and Amerindians. This interpretation is insufficient to explain the coincidence of the cline in England and Chile, and for some findings in Chile. 1) The A and Rh(-) frequencies of the highest SES in Chile are significantly higher than those found in Europeans. 2) The B gene and phenotypes (with AB) behave differently and in contradiction to the socio-ethno-cultural-historical process. 3) There is a significant interaction of the SGC with gender in Chile and England. There is not at present a putative relationship between ABO and psycho-social factors that could account for this sociogenetic interaction. This SGC seems to be present in societies with a hierarchical organization in relation to power, prestige, ownership, income and life style, and when sampling includes the most extreme SES. It has not been found in two samples from Ireland and in a sample from Chile taken from a public hospital, probably because those variables and conditions were not ascertained.

Heterogeneous periodicity of drosophila mtDNA: new refutations of neutral and nearly neutral evolution

We found a consistent 3-site periodicity of the X²9 values for the heterogeneity of the distribution of the second base in relation to the first base of dinucleotides separated by 0 (contiguous), 1, 2, 3 ... 17 (K) nucleotide sites in Drosophila mtDNA. Triplets of X²9 values were found where the first was over 300 and the second and third ranged between 37 and 114 (previous studies). In this study, the periodicity was significant until separation of 2011K, and a structure of deviations from randomness among dinucleotides was found. The most deviant dinucleotides were G-G, G-C and C-G for the first, second and third element of the triplet, respectively. In these three cases there were more dinucleotides observed than expected. This inter-bases correlation and periodicity may be related to the tertiary structure of circular DNA, like that of prokaryotes and mitochondria, to protect and preserve it. The mtDNA with 19.517 bp was divided into four equal segments of 4.879 bp. The fourth sub-segment presented a very low proportion of G and C, the internucleotide interaction was weaker in this sub-segment and no periodicity was found. The maintenance of this mtDNA structure and organization for millions of generations, in spite of a high recurrent mutation rate, does not support the notion of neutralism or near neutralism. The high level of internucleotide interaction and periodicity indicate that every nucleotide is co-adapted with the residual genome.

Sexual orientation, handedness, sex ratio and fetomaternal tolerance-rejection

Fraternal birth order (FBO) appears as a prenatal cause of 15 percent of homosexual males (gays) through mnemonic maternal anti-male factors. Non-right-handed men seem to be protected from homosexuality. Four hypotheses are proposed: (1) androgenic factors of non-right-handedness neutralize anti-male factors; (2) non-right-handedness and homosexuality are lethal or produce mental impairment; (3) non-right-handed male embryos are insensitive to anti-male factors; (4) mothers of non-right-handed fetuses do not produce anti-male factors. Studies of the sex ratio (SR) of older and younger siblings show: (1) a significant heterogeneity in the SR of siblings of right or non-right handed heterosexual men and women; (2) lesbians are born among siblings with high SR; (3) siblings of right-handed gays show a higher SR than non-right-handed gays that present a low SR. Based on our discovery of maternal tolerance-rejection processes, associated with genetic systems (ABO, Rh), where zygotes or embryos different from their mother induce better pregnancy and maternal tolerance than do those that share antigens with their mothers, I propose a new explanation for sexual relationships, sexual orientation, handedness and sibling SR. Lesbian embryos could induce tolerance from mothers with anti-female factors. Non-right-handedness could induce maternal tolerance, or change the maternal compatibility of "gay" embryos. Alternatively, gay embryos could be poor inducers of maternal tolerance towards male traits.

Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: New evidence for panselective evolution

Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA), the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x²9) was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.

Fixations of the HIV-1 env gene refute neutralism: New evidence for pan-selective evolution

We examined 103 nucleotide sequences of the HIV-1 env gene, sampled from 35 countries and tested: I) the random (neutral) distribution of the number of nucleotide changes; II) the proportion of bases at molecular equilibrium; III) the neutral expected homogeneity of the distribution of new fxated bases; IV) the hypothesis of the neighbor infuence on the mutation rates in a site. The expected random number of fxations per site was estimated by Bose-Einstein statistics, and the expected frequencies of bases by matrices of mutation-fxation rates. The homogeneity of new fxations was analyzed using χ2 and trinomial tests for homogeneity. Fixations of the central base in trinucleotides were used to test the neighbor infuence on base substitutions. Neither the number of fxations nor the frequencies of bases ftted the expected neutral distribution. There was a highly signifcant heterogeneity in the distribution of new fxations, and several sites showed more transversions than transitions, showing that each nucleotide site has its own pattern of change. These three independent results make the neutral theory, the nearly neutral and the neighbor infuence hypotheses untenable and indicate that evolution of env is rather highly selective.