浅谈海洋无脊椎动物的生物钟

一般动物(含人类)的生理活动和行为都有不同程度的周期性(periodicity)或节奏性(rhythemicity),而这些现象的表现并不一致:有的较明显,很易发觉(如昼夜垂直移动、体色变化等),而有的较隐蔽,不易发现(如视网膜色素移动等)。生物钟(biological clock)是受时间机制(timing mechanism)调节或控制的一种节奏性或周期性的生理活动(较为隐蔽)     

A lunar clock changes shielding pigment transparency in larval ocelli of Clunio marinus

Living in the tidal zones of the sea requires synchronization with the dominant environmental influences of tidal, solar, and lunar periodicity. Endogenous clocks anticipate those geoclimatic changes and control the respective rhythms of vital functions. But the underlying mechanisms are only partly understood. While the circadian clocks in animals are investigated employing neurobiological, molecular, and genetic approaches, clocks with a lunar periodicity have been studied with reference to development and behavior only. Sites of their pacemakers, zeitgeber receptors, and coupled endocrine components are unknown. Here, a lunar-rhythmic change of shielding pigment transparency in the larval ocelli of the intertidal midge Clunio marinus is demonstrated for the first time as a possible access to the neurobiology of lunar timing mechanisms. We studied third instar larvae (Vigo strain) throughout the lunar cycle by light- and electron-microscopy as well as by x-ray fluorescence analysis for the identification of the pigment. Moonlight detection is a prerequisite for photic synchronization of the lunar clock. The larval ocelli of Clunio putatively may function as moonlight receptors and are also controlled by the circalunar clock itself, hence being primary candidates for tracing input and output pathways of the lunar pacemaker. Additionally, the demonstration of a reversible optical change of shielding pigment transparency in Clunio is a novel finding, not reported so far in any other animal species, and reveals a mechanism to enhance photosensitivity under the condition of very dim light. It represents a remarkable change of a sense organ from an imaging device to a radiometer. Its restriction to the developmental stage susceptible to lunar timing elucidates a unique sensory strategy evolved at the level of sensory input. It also raises basic questions about the biochemistry of optically active pigments, like melanin, and their intracellular control.     

Circadian components of semilunar and lunar timing mechanisms

The timing of semilunar as well as lunar reproductive rhythms has been analyzed in different geographic populations of the intertidal chironomid Clunio. In stocks of three populations differing in period and phase relationship with the lunar month, these long-term rhythms were synchronized in the laboratory by using artificial moonlight cycles of 30 days in otherwise 24-hr light-dark (LD) cycles (0.4 lux during 4 successive nights every 30 days in LD 12:12). In LD cycles of various periods, a strong synchronization was only possible in LD 12:12 and LD 11:11, whereas in LD 10:10 and LD 15:15 the synchronization by the 30-"day" moonlight cycle was weak or even absent. The study demonstrates a limited range of circadian periods for entrainment of the long-term rhythms. It is concluded that an LD cycle with a period near 24 hr is an essential zeitgeber condition for semilunar and lunar timing in this marine insect. Further, it is suggested that the underlying physiological timing mechanism of Clunio consists of a circadian function for the perception of the monthly moonlight zeitgeber cycles that entrain the endogenous, temperature-compensated oscillator of the circasemilunar (or circalunar) period. The long-term oscillator triggers the metamorphosis of the insect, and thereby determines the time of its eclosion and reproduction on the shorelines, in correlation with days of spring tides recurring about every 14-15 days.     

The use of mouse models to unravel genetic architecture of physical activity: a review

The discovery of genetic variants that underlie a complex phenotype is challenging. One possible approach to facilitate this endeavor is to identify quantitative trait loci (QTL) that contribute to the phenotype and consequently unravel the candidate genes within these loci. Each proposed candidate locus contains multiple genes and, therefore, further analysis is required to choose plausible candidate genes. One of such methods is to use comparative genomics in order to narrow down the QTL to a region containing only a few genes. We illustrate this strategy by applying it to genetic findings regarding physical activity (PA) in mice and human. Here, we show that PA is a complex phenotype with a strong biological basis and complex genetic architecture. Furthermore, we provide considerations for the translatability of this phenotype between species. Finally, we review studies which point to candidate genetic regions for PA in humans (genetic association and linkage studies) or use mouse models of PA (QTL studies) and we identify candidate genetic regions that overlap between species. On the basis of a large variety of studies in mice and human, statistical analysis reveals that the number of overlapping regions is not higher than expected on a chance level. We conclude that the discovery of new candidate genes for complex phenotypes, such as PA levels, is hampered by various factors, including genetic background differences, phenotype definition and a wide variety of methodological differences between studies .     

A Lunar Clock Changes Shielding Pigment Transparency in Larval Ocelli of Clunio marinus

Living in the tidal zones of the sea requires synchronization with the dominant environmental influences of tidal, solar, and lunar periodicity. Endogenous clocks anticipate those geoclimatic changes and control the respective rhythms of vital functions. But the underlying mechanisms are only partly understood. While the circadian clocks in animals are investigated employing neurobiological, molecular, and genetic approaches, clocks with a lunar periodicity have been studied with reference to development and behavior only. Sites of their pacemakers, zeitgeber receptors, and coupled endocrine components are unknown. Here, a lunar‐rhythmic change of shielding pigment transparency in the larval ocelli of the intertidal midge Clunio marinus is demonstrated for the first time as a possible access to the neurobiology of lunar timing mechanisms. We studied third instar larvae (Vigo strain) throughout the lunar cycle by light‐ and electron-microscopy as well as by x‐ray fluorescence analysis for the identification of the pigment. Moonlight detection is a prerequisite for photic synchronization of the lunar clock. The larval ocelli of Clunio putatively may function as moonlight receptors and are also controlled by the circalunar clock itself, hence being primary candidates for tracing input and output pathways of the lunar pacemaker. Additionally, the demonstration of a reversible optical change of shielding pigment transparency in Clunio is a novel finding, not reported so far in any other animal species, and reveals a mechanism to enhance photosensitivity under the condition of very dim light. It represents a remarkable change of a sense organ from an imaging device to a radiometer. Its restriction to the developmental stage susceptible to lunar timing elucidates a unique sensory strategy evolved at the level of sensory input. It also raises basic questions about the biochemistry of optically active pigments, like melanin, and their intracellular control.     

Quantitative trait loci for floral morphology in Arabidopsis thaliana

A central question in biology is how genes control the expression of quantitative variation. We used statistical methods to estimate genetic variation in eight Arabidopsis thaliana floral characters (fresh flower mass, petal length, petal width, sepal length, sepal width, long stamen length, short stamen length, and pistil length) in a cosmopolitan sample of 15 ecotypes. In addition, we used genome-wide quantitative trait locus (QTL) mapping to evaluate the genetic basis of variation in these same traits in the Landsberg erecta x Columbia recombinant inbred line population. There was significant genetic variation for all traits in both the sample of naturally occurring ecotypes and in the Ler x Col recombinant inbred line population. In addition, broad-sense genetic correlations among the traits were positive and high. A composite interval mapping (CIM) analysis detected 18 significant QTL affecting at least one floral character. Eleven QTL were associated with several floral traits, supporting either pleiotropy or tight linkage as major determinants of flower morphological integration. We propose several candidate genes that may underlie these QTL on the basis of positional information and functional arguments. Genome-wide QTL mapping is a promising tool for the discovery of candidate genes controlling morphological development, the detection of novel phenotypic effects for known genes, and in generating a more complete understanding of the genetic basis of floral development.     

QTL mapping in a mouse model of cardiomyopathy reveals an ancestral modifier allele affecting heart function and survival

The progression from myocardial hypertrophy to heart failure is a complex process, involving genetic and environmental factors. Elucidating the genetic components contributing to heart failure has been difficult, largely because of the heterogeneity of human populations. We have employed a strategy to map genetic loci that modify the heart failure phenotype in a transgenic mouse model of cardiomyopathy caused by cardiac-specific overexpression of calsequestrin. Strain-specific differences in both cardiac function and survival are observed when the transgene is moved into different inbred mouse strains. We have previously reported linkage results from mapping in reciprocal backcrosses between C57/BL6 (BL6) and DBA/2J (DBA) and a backcross between DBA/AKR and AKR. Here we report the results of a genome-wide linkage scan in the reciprocal backcross between DBA/AKR and DBA. We identified one novel locus on Chromosome (Chr) 18 that affects heart function and a second on Chr 3 that shows significant linkage to both survival and heart function. Intriguingly, the Chr 3 allele of AKR shows a susceptibility effect on phenotype, whereas the overall effect of the AKR genetic background is protective. The Chr 3 locus also completely overlaps the Hrtfm2 locus, which was previously mapped in crosses between DBA and BL6. Mapping the same QTL in two different crosses allowed us to use ancestral haplotypes to narrow the candidate gene interval from 9 to 2 Mb. Identification of the genes at these QTLs in the mouse will provide novel candidate genes that can be evaluated for their role in human heart failure.     

Quantitative trait loci for inflorescence development in Arabidopsis thaliana

Variation in inflorescence development patterns is a central factor in the evolutionary ecology of plants. The genetic architectures of 13 traits associated with inflorescence developmental timing, architecture, rosette morphology, and fitness were investigated in Arabidopsis thaliana, a model plant system. There is substantial naturally occurring genetic variation for inflorescence development traits, with broad sense heritabilities computed from 21 Arabidopsis ecotypes ranging from 0.134 to 0.772. Genetic correlations are significant for most (64/78) pairs of traits, suggesting either pleiotropy or tight linkage among loci. Quantitative trait locus (QTL) mapping indicates 47 and 63 QTL for inflorescence developmental traits in Ler x Col and Cvi x Ler recombinant inbred mapping populations, respectively. Several QTL associated with different developmental traits map to the same Arabidopsis chromosomal regions, in agreement with the strong genetic correlations observed. Epistasis among QTL was observed only in the Cvi x Ler population, and only between regions on chromosomes 1 and 5. Examination of the completed Arabidopsis genome sequence in three QTL regions revealed between 375 and 783 genes per region. Previously identified flowering time, inflorescence architecture, floral meristem identity, and hormone signaling genes represent some of the many candidate genes in these regions.     

Another place, another timer: Marine species and the rhythms of life

The marine ecosystem is governed by a multitude of environmental cycles, all of which are linked to the periodical recurrence of the sun or the moon. In accordance with these cycles, marine species exhibit a variety of biological rhythms, ranging from circadian and circatidal rhythms to circalunar and seasonal rhythms. However, our current molecular understanding of biological rhythms and clocks is largely restricted to solar-controlled circadian and seasonal rhythms in land model species. Here, we discuss the first molecular data emerging for circalunar and circatidal rhythms and present selected species suitable for further molecular analyses. We argue that a re-focus on marine species will be crucial to understand the principles, interactions and evolution of rhythms that govern a broad range of eukaryotes, including ourselves.     

The candidate gene, Clock, localizes to a strong spawning time quantitative trait locus region in rainbow trout

We applied a candidate gene mapping approach to an existing quantitative trait loci (QTL) data set for spawning date in rainbow trout (Oncorynchus mykiss) to ascertain whether these genes could potentially account for any observed QTL effects. Several genes were chosen for their known or suspected roles in reproduction, circadian, or circannual timing, including salmon-type gonadotropin-releasing hormone 3A and 3B (GnRH3A and GnRH3B), Clock, Period1, and arylalkylamine N-acetlytransferase-1 and -2 (AANAT-1 and AANAT-2). Genes were sequenced, and polymorphisms were identified in parents of two rainbow trout mapping families, one of which was used previously to detect spawn timing QTL. Interval mapping was used to identify associations between genetic markers and spawning date effects. Using a genetic map that was updated with 574 genetic markers (775 total), we found evidence for 11 significant or suggestive QTL regions. Most QTL were only localized within one of the parents; however, a strong QTL region was identified in both female and male parents on linkage group RT-8 that explained 20% and 50% of trait variance, respectively. The Clock gene mapped to this region. Period1 mapped to a region in the female parent associated with a marginal effect (P = .056) on spawn timing. Other candidate genes were not associated with significant QTL effects.     

Genomic arrangement of salinity tolerance QTLs in salmonids: A comparative analysis of Atlantic salmon (Salmo salar) with Arctic charr (Salvelinus alpinus) and rainbow trout (

ABSTRACT: BACKGROUND: Quantitative trait locus (QTL) studies show that variation in salinity tolerance in Arctic charr and rainbow trout has a genetic basis, even though both these species have low to moderate salinity tolerance capacities. QTL were observed to localize to homologous linkage group segments within putative chromosomal regions possessing multiple candidate genes. We compared salinity tolerance QTL in rainbow trout and Arctic charr to those detected in a higher salinity tolerant species, Atlantic salmon. The highly derived karyotype of Atlantic salmon allows for the assessment of whether disparity in salinity tolerance in salmonids is associated with differences in genetic architecture. To facilitate these comparisons, we examined the genomic synteny patterns of key candidate genes in the other model teleost fishes that have experienced three whole-genome duplication (3R) events which preceded a fourth (4R) whole genome duplication event common to all salmonid species. RESULTS: Nine linkage groups contained chromosome-wide significant QTL (AS-2, -4p, -4q, -5, -9, -12p, -12q, -14q -17q, -22, and [MINUS SIGN]23), while a single genome-wide significant QTL was located on AS-4q. Salmonid genomes shared the greatest marker homology with the genome of three-spined stickleback. All linkage group arms in Atlantic salmon were syntenic with at least one stickleback chromosome, while 18 arms had multiple affinities. Arm fusions in Atlantic salmon were often between multiple regions bearing salinity tolerance QTL. Nine linkage groups in Arctic charr and six linkage group arms in rainbow trout currently have no synteny alignments with stickleback chromosomes, while eight rainbow trout linkage group arms were syntenic with multiple stickleback chromosomes. Rearrangements in the stickleback lineage involving fusions of ancestral arm segments could account for the 21 chromosome pairs observed in the stickleback karyotype. CONCLUSIONS: Salinity tolerance in salmonids from three genera is to some extent controlled by the same loci. Synteny between QTL in salmonids and candidate genes in stickleback suggests genetic variation at candidate gene loci could affect salinity tolerance in all three salmonids investigated. Candidate genes often occur in pairs on chromosomes, and synteny patterns indicate these pairs are generally conserved in 2R, 3R, and 4R genomes. Synteny maps also suggest that the Atlantic salmon genome contains three larger syntenic combinations of candidate genes that are not evident in any of the other 2R, 3R, or 4R genomes examined. These larger synteny tracts appear to have resulted from ancestral arm fusions that occurred in the Atlantic salmon ancestor. We hypothesize that the superior hypo-osmoregulatory efficiency that is characteristic of Atlantic salmon may be related to these clusters.     

Flowering time and transcriptome variation in Capsella bursa-pastoris (Brassicaceae)

? Flowering is a major developmental transition and its timing in relation to environmental conditions is of crucial importance to plant fitness. Understanding the genetic basis of flowering time variation is important to determining how plants adapt locally. ? Here, we investigated flowering time variation of Capsella bursa-pastoris collected from different latitudes in China. We also used a digital gene expression (DGE) system to generate partial gene expression profiles for 12 selected samples. ? We found that flowering time was highly variable and most strongly correlated with day length and winter temperature. Significant differences in gene expression between early- and late-flowering samples were detected for 72 candidate genes for flowering time. Genes related to circadian rhythms were significantly overrepresented among the differentially expressed genes. ? Our data suggest that circadian rhythms and circadian clock genes play an important role in the evolution of flowering time, and C. bursa-pastoris plants exhibit expression differences for candidate genes likely to affect flowering time across the broad range of environments they face in China.     

Finding the molecular basis of quantitative traits: successes and pitfalls

Understanding the molecular basis of quantitative genetic variation is a principal goal for biomedicine. Although the complex genetic architecture of quantitative traits has so far largely frustrated attempts to identify genes in humans by standard linkage methodologies, quantitative trait loci (QTL) have been mapped in plants, insects and rodents. However, identifying the molecular bases of QTL remains a challenge. Here, we discuss why this is and how new experimental strategies and analytical techniques, combined with the fruits of the genome projects, are beginning to identify candidate genes for QTL studies in several model organisms.     

The brain's calendar: neural mechanisms of seasonal timing

The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal component of the mammalian biological clock, the neural timing system that generates and coordinates a broad spectrum of physiological, endocrine and behavioural circadian rhythms. The pacemaker of the SCN oscillates with a near 24 h period and is entrained to the diurnal light-dark cycle. Consistent with its role in circadian timing, investigations in rodents and non-human primates furthermore suggest that the SCN is the locus of the brain's endogenous calendar, enabling organisms to anticipate seasonal environmental changes. The present review focuses on the neuronal organization and dynamic properties of the biological clock and the means by which it is synchronized with the environmental lighting conditions. It is shown that the functional activity of the biological clock is entrained to the seasonal photic cycle and that photoperiod (day length) may act as an effective zeitgeber. Furthermore, new insights are presented, based on electrophysiological and molecular studies, that the mammalian circadian timing system consists of coupled oscillators and that the clock genes of these oscillators may also function as calendar genes. In summary, there are now strong indications that the neuronal changes and adaptations in mammals that occur in response to a seasonally changing environment are driven by an endogenous circadian clock located in the SCN, and that this neural calendar is reset by the seasonal fluctuations in photoperiod.     

Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas-fir. IV. Cold-hardiness QTL verification and candidate gene mapping

Quantitative trait locus (QTL) analyses are used by geneticists to characterize the genetic architecture of quantitative traits, provide a foundation for marker-aided-selection (MAS), and provide a framework for positional selection of candidate genes. The most useful QTL for breeding applications are those that have been verified in time, space, and/or genetic background. In this study, spring cold-hardiness of Douglas-fir foliar tissues was evaluated in two clonally replicated (n=170 and 383 clones) full-sib cohorts derived from the same parental cross in two different years (made 5 years apart). The cohorts were established in widely separated forest test sites and tissues were artificially freeze tested using different cold injury assessment methods. Four of six unique QTL detected for spring cold-hardiness in needles of Cohort 1 were tentatively verified in the second cohort. Four additional QTL were detected in Cohort 2, two on linkage groups (LGs) not previously represented in the smaller cohort. In total, 10 unique QTL were identified across both cohorts. Seventeen of twenty-nine putative cold-hardiness candidate genes (Douglas-fir ESTs) placed on the Douglas-fir linkage map locate within the 95% confidence intervals of spring needle cold-hardiness QTL from the two cohorts and thus represent priority targets for initiating association mapping in Douglas-fir.     

High-resolution mapping of the blood pressure QTL on chromosome 7 using Dahl rat congenic strains

It was previously shown using Dahl salt-sensitive (S) and salt-resistant (R) rats that a blood pressure quantitative trait locus (QTL) was present on rat chromosome 7. In the present work, this QTL was localized to a region less than 0.54 cM in size on the linkage map using a series of congenic strains. This region was contained in a single yeast artificial chromosome that was 220 kb long. This small segment still contained the primary candidate locus Cyp11b1 (11beta-hydroxylase), but the adjacent candidate genes Cyp11b2 (aldosterone synthase) and Cyp11b3 were ruled out. It is concluded that 11beta-hydroxylase, through its known genetic variants altering the production of 18-hydroxy-11-deoxy corticosterone, is very likely to account for the blood pressure QTL on chromosome 7 in the Dahl rat model of hypertension. This QTL accounts for about 23 mm Hg under the condition of 2% NaCl diet for 24 days.     

Comparison of quantitative trait loci for adaptive traits between oak and chestnut based on an expressed sequence tag consensus map

A comparative genetic and QTL mapping was performed between Quercus robur L. and Castanea sativa Mill., two major forest tree species belonging to the Fagaceae family. Oak EST-derived markers (STSs) were used to align the 12 linkage groups of the two species. Fifty-one and 45 STSs were mapped in oak and chestnut, respectively. These STSs, added to SSR markers previously mapped in both species, provided a total number of 55 orthologous molecular markers for comparative mapping within the Fagaceae family. Homeologous genomic regions identified between oak and chestnut allowed us to compare QTL positions for three important adaptive traits. Colocation of the QTL controlling the timing of bud burst was significant between the two species. However, conservation of QTL for height growth was not supported by statistical tests. No QTL for carbon isotope discrimination was conserved between the two species. Putative candidate genes for bud burst can be identified on the basis of colocations between EST-derived markers and QTL.