生物软件在序列分析过程中的运用

介绍了组合使用BLAST、FASTA/BLASTScan3.2,或用多序列比对软件,从数据库中快速提取大数量目标序列,最后用MEGA4快捷编辑整理大数量序列的方法。还介绍了一种生成核酸序列与其氨基酸序列相似性百分率整合表格的方法。简述了对引物设计的基本认识并介绍了多重引物兼容性筛选软件;对构建系统发育树的认识并引出分子进化树构建软件MEGA4的使用和PAUP 4.0常用建树命令模块。期望这些方法和软件的使用能解决生物序列分析过程的常见问题。     

Surprising negative association between IgG1 allotype disparity and anti-adalimumab formation: a cohort study

Introduction

The human monoclonal antibody adalimumab is known to induce an anti-globulin response in some adalimumab-treated patients. Antibodies against adalimumab (AAA) are associated with non-response to treatment. Immunoglobulins, such as adalimumab, carry allotypes which represent slight differences in the amino acid sequences of the constant chains of an IgG molecule. Immunoglobulins with particular IgG (Gm) allotypes are racially distributed and could be immunogenic for individuals who do not express these allotypes. Therefore, we investigated whether a mismatch in IgG allotypes between adalimumab and IgG in adalimumab-treated patients is associated with the development of AAA.

Methods

This cohort study consisted of 250 adalimumab-treated rheumatoid arthritis (RA) patients. IgG allotypes were determined for adalimumab and for all patients. Anti-idiotype antibodies against adalimumab were measured with a regular radio immunoassay (RIA), and a newly developed bridging enzyme linked immunosorbent assay (ELISA) was used to measure anti-allotype antibodies against adalimumab. The association between AAA and the G1m3 and the G1m17 allotypes was determined. For differences between groups we used the independent or paired samples t-test, Mann-Whitney test or Chi square/Fisher's exact test as appropriate. To investigate the influence of confounders on the presence or absence of AAA a multiple logistic regression-analysis was used.

Results

Adalimumab carries the G1m17 allotype. No anti-allotype antibodies against adalimumab were detected. Thirty-nine out of 249 patients had anti-idiotype antibodies against adalimumab (16%). IgG allotypes of RA patients were associated with the frequency of AAA: patients homozygous for G1m17 had the highest frequency of AAA (41%), patients homozygous for G1m3 the lowest frequency (10%), and heterozygous patients' AAA frequency was 14% (P = 0.0001).

Conclusions

An allotype mismatch between adalimumab and IgG in adalimumab-treated patients did not lead to a higher frequency of AAA. On the contrary, patients who carried the same IgG allotype as present on the adalimumab IgG molecule, had the highest frequency of anti-adalimumab antibodies compared to patients whose IgG allotype differed from adalimumab. This suggests that the allotype of adalimumab may not be highly immunogenic. Furthermore, patients carrying the G1m17-allotype might be more prone to antibody responses.     

Male Drosophila melanogaster have higher mating success when adapted to their thermal environment

Adaptation to new environments is a well-documented phenomenon. Individuals from populations maintained in a particular environment for multiple generations tend to be better able to survive and/or reproduce in that environment than their ancestors or other individuals adapted to alternative environments. A third major component of fitness, mating success, has not been well studied in replicated populations under selection in divergent environments. In this study, we used mating trials to compare the mating success of male Drosophila melanogaster adapted for 10 years to two different temperatures, 18 and 25 degrees C. In competition for female partners, males had significantly higher mating success at their adapted temperature compared with males adapted to a different temperature. These results are consistent with the notion that those mutations favoured by natural selection also tend to be favoured by sexual selection.     

The variance in inbreeding depression and the recovery of fitness in bottlenecked populations

Theoretical analyses of inbreeding suggest that following an increased degree of inbreeding there may be a temporary recovery of fitness, because of selection either within or among inbred lineages. This is possible because selection can act more efficiently to remove deleterious alleles given the greater homozygosity of such populations. If common, recovery of fitness following inbreeding may be important for understanding some evolutionary processes and for management strategies of remnant populations, yet empirical evidence for such recovery in animals is scant. Here we describe the effects of single-pair population bottlenecks on a measure of fitness in Drosophila melanogaster. We compared a large number of families from each of 52 inbred lines with many families from the outbred population from which the inbred lineages were derived. Measures were made at the third and the 20th generations after the bottleneck. In both generations there was, on average, substantial inbreeding depression together with a highly significant variance among the inbred lines in the amount of fitness reduction. The average fitness of inbred lines was correlated across generations. Our data provide evidence for the possibility of recovery of fitness at two levels, because (i) the average fitness reduction in the F20 generation was significantly less than in the F3 generation, which implies that selection within lines has occurred, and (ii) the large variance in inbreeding depression among inbred lines implies that selection among them is possible. The high variance in inbreeding depression among replicate lines implies that modes of evolution which require a low level of inbreeding depression can function at least in a fraction of inbred populations within a species and that results from studies with low levels of replication should be treated with caution.     

The changes in genetic and environmental variance with inbreeding in Drosophila melanogaster

We performed a large-scale experiment on the effects of inbreeding and population bottlenecks on the additive genetic and environmental variance for morphological traits in Drosophila melanogaster. Fifty-two inbred lines were created from the progeny of single pairs, and 90 parent-offspring families on average were measured in each of these lines for six wing size and shape traits, as well as 1945 families from the outbred population from which the lines were derived. The amount of additive genetic variance has been observed to increase after such population bottlenecks in other studies; in contrast here the mean change in additive genetic variance was in very good agreement with classical additive theory, decreasing proportionally to the inbreeding coefficient of the lines. The residual, probably environmental, variance increased on average after inbreeding. Both components of variance were highly variable among inbred lines, with increases and decreases recorded for both. The variance among lines in the residual variance provides some evidence for a genetic basis of developmental stability. Changes in the phenotypic variance of these traits are largely due to changes in the genetic variance.     

Perspective: Evolution and detection of genetic robustness

Abstract Robustness is the invariance of phenotypes in the face of perturbation. The robustness of phenotypes appears at various levels of biological organization, including gene expression, protein folding, metabolic flux, physiological homeostasis, development, and even organismal fitness. The mechanisms underlying robustness are diverse, ranging from thermodynamic stability at the RNA and protein level to behavior at the organismal level. Phenotypes can be robust either against heritable perturbations (e.g., mutations) or nonheritable perturbations (e.g., the weather). Here we primarily focus on the first kind of robustness–genetic robustness–and survey three growing avenues of research: (1) measuring genetic robustness in nature and in the laboratory; (2) understanding the evolution of genetic robustness; and (3) exploring the implications of genetic robustness for future evolution.     

The genetics of adaptation: the roles of pleiotropy, stabilizing selection and drift in shaping the distribution of bidirectional fixed mutational effects

Pleiotropy allows for the deterministic fixation of bidirectional mutations: mutations with effects both in the direction of selection and opposite to selection for the same character. Mutations with deleterious effects on some characters can fix because of beneficial effects on other characters. This study analytically quantifies the expected frequency of mutations that fix with negative and positive effects on a character and the average size of a fixed effect on a character when a mutation pleiotropically affects from very few to many characters. The analysis allows for mutational distributions that vary in shape and provides a framework that would allow for varying the frequency at which mutations arise with deleterious and positive effects on characters. The results show that a large fraction of fixed mutations will have deleterious pleiotropic effects even when mutation affects as little as two characters and only directional selection is occurring, and, not surprisingly, as the degree of pleiotropy increases the frequency of fixed deleterious effects increases. As a point of comparison, we show how stabilizing selection and random genetic drift affect the bidirectional distribution of fixed mutational effects. The results are then applied to QTL studies that seek to find loci that contribute to phenotypic differences between populations or species. It is shown that QTL studies are biased against detecting chromosome regions that have deleterious pleiotropic effects on characters.     

Estimating effective population size and migration rates from genetic samples over space and time

In the past, moment and likelihood methods have been developed to estimate the effective population size (N(e)) on the basis of the observed changes of marker allele frequencies over time, and these have been applied to a large variety of species and populations. Such methods invariably make the critical assumption of a single isolated population receiving no immigrants over the study interval. For most populations in the real world, however, migration is not negligible and can substantially bias estimates of N(e) if it is not accounted for. Here we extend previous moment and maximum-likelihood methods to allow the joint estimation of N(e) and migration rate (m) using genetic samples over space and time. It is shown that, compared to genetic drift acting alone, migration results in changes in allele frequency that are greater in the short term and smaller in the long term, leading to under- and overestimation of N(e), respectively, if it is ignored. Extensive simulations are run to evaluate the newly developed moment and likelihood methods, which yield generally satisfactory estimates of both N(e) and m for populations with widely different effective sizes and migration rates and patterns, given a reasonably large sample size and number of markers.     

雅鲁藏布江中游浮游植物群落优势种时空生态位

为探究雅鲁藏布江中游浮游植物群落分布格局及其优势种时空生态位特征,于2021年7月、10月对该水域进行浮游植物样品的采集和水体理化因子的测定,鉴定浮游植物物种,计算浮游植物优势种生态位宽度、生态位重叠值、生态响应速率及相对资源占有率,运用共现网络模型分析群落的种间关联性,并对浮游植物优势种与环境因子进行Pearson相关性分析。结果表明：该水域共鉴定到浮游植物644种,隶属于8门12纲25目49科152属,其中,优势种22种,优势种中硅藻占90.9%,在群落中占绝对优势;丰水期的肘状针杆藻丰度最大(74.193×10⁴细胞/L)且出现频率最高(0.867),是丰水期绝对优势种;整体上优势种生态位宽度时间(0.833)>空间(0.254),优势种时空生态位宽度主要受空间生态位宽度的影响,空间异质性是影响该水域浮游植物优势种分布的主要因素;优势种时空二维生态位无意义重叠的种对占40.69%,优势种时空二维的生态位重叠以中、低等级为主,优势种间对时空资源需求异质性高,种间潜在竞争关系较弱;该水域枯水期浮游植物群落的网络结构紧密,群落连通性、群落复杂度和物种间生态位...