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Biomedical subjects

J D Mollon

Publications and source records attributed to J D Mollon.

At least 55 records · Page 3Linked to original sources

Adaptive evolution of color vision genes in higher primates.

The intron 4 sequences of the three polymorphic alleles at the X-linked color photo-pigment locus in the squirrel monkey and the marmoset reveal that the alleles in each species are exceptionally divergent. The data further suggest either that each triallelic system has arisen independently in these two New World monkey lineages, or that in each species at least seven deletions and insertions (14 in the two species) in intron 4 have been transferred and homogenized among the alleles by gene conversion or recombination. In either case, the alleles in each species apparently have persisted more than 5 million years and probably have been maintained by overdominant selection.

Alleles↗

Sequence and evolution of the blue cone pigment gene in Old and New World primates.

The sequences of the blue cone photopigments in the talapoin monkey (Miopithecus talapoin), an Old World primate, and in the marmoset (Callithrix jacchus), a New World monkey, are presented. Both genes are composed of 5 exons separated by 4 introns. In this respect, they are identical to the human blue gene, and intron sizes are also similar. Based on the level of amino acid identity, both monkey pigments are members of the S branch of pigments. Alignment of these sequences with the human gene requires the insertion/deletion of two separate codons in exon 1. The silent site divergence between these primate blue genes indicates a separation of the Old and New World primate lineages around 43 million years ago.

Amino Acid Sequence↗

Colour constancy influenced by contrast adaptation.

Visual sensitivity is controlled by at least two distinct types of adaptation: light adaptation adjusts sensitivity to the mean luminance and colour in the stimulus, and contrast adaptation adjusts sensitivity to the variations in luminance and colour. Light adaptation is thought to be important in maintaining the perceived colour of objects despite changes in illumination ('colour constancy'), compensating for the mean changes in the light reflected from scenes under different illuminants. But for naturalistic colour signals, we show here that changes in an illuminant can also alter colour contrasts in images (how colours are distributed around the mean) enough to alter the state of contrast adaptation. Thus perceived colour under different illuminants may also be noticeably influenced by contrast adaptation.

Adaptation, Ocular↗

The chemistry of John Dalton's color blindness.

John Dalton described his own color blindness in 1794. In common with his brother, he confused scarlet with green and pink with blue. Dalton supposed that his vitreous humor was tinted blue, selectively absorbing longer wavelengths. He instructed that his eyes should be examined after his death, but the examination revealed that the humors were perfectly clear. In experiments presented here, DNA extracted from his preserved eye tissue showed that Dalton was a deuteranope, lacking the middlewave photopigment of the retina. This diagnosis is shown to be compatible with the historical record of his phenotype, although it contradicts Thomas Young's belief that Dalton was a protanope.

Base Sequence↗

Rayleigh matches and unique green.

There are recurrent reports that Rayleigh matches are bimodally distributed in the colour-normal male population. Similar claims have been made for the distribution of the spectral locus of unique green. Moreover, a positive correlation has sometimes been reported between Rayleigh matches and unique green. Using a computer-controlled Maxwellian colorimeter and bias-free psychophysical methods, we measured both variables for 97 colour-normal male observers. We do not find a bimodal distribution either of Rayleight matches or of settings of unique green. Nor do we find any correlation between the two variables. However, we do observe a very significant relationship between the lightness of the subject's iris and the wavelength that he judges to be unique green.

Adaptation, Ocular↗

CAG repeat expansions and schizophrenia: association with disease in females and with early age-at-onset.

An increase in the severity of schizophrenia through consecutive generations (anticipation) has been found in some studies of families with affected members. Anticipation in five neurological disorders is known to arise from the expansion of CAG repeats between generations of affected individuals. The 'repeat expansion detection' method was used to screen individual genomes for the size of such expansions in a sample of schizophrenic and normal subjects. Comparison of the frequency distribution of CAG expansions observed in schizophrenic patients to that for normal subjects, showed that there are significantly more expansions in patients (p = 0.048). When male and female subjects are considered separately, there is a highly significant difference in the distribution of repeat sizes found between affected and normal females (p = 0.0023) but no significant difference between affected and normal males. Overall there is a 28% excess of expansions observed in affected versus normal females, and their presence confers a relative risk of 4.12 (p < 0.005). In contrast, the frequency distribution of age-at-onset with respect to repeat size is nearly the same in male and female patients and, when the sexes are combined, the larger (CAG)69-136 expansions are associated with a younger age-at-onset (p = 0.02).

Adolescent↗

The influence of contrast adaptation on color appearance.

Most models of color vision assume that signals from the three classes of cone receptor are recoded into only three independent post-receptoral channels: one that encodes luminance and two that encode color. Stimuli that are equated for their effects on two of the channels should be discriminable only to the remaining channel, and are thus assumed to isolate the responses of single channels. We used an asymmetric matching task to examine whether such models can account for changes in color appearance following adaptation to contrast--to temporal variations in luminance and chromaticity around a fixed mean luminance and chromaticity. The experiments extend to suprathreshold color appearance the threshold adaptation paradigm of Krauskopf, Williams and Heeley [(1982) Vision Research, 32, 1123-1131]. Adaptation changes the perceived color of chromatic test stimuli both by reducing their saturation (contrast) and by changing their hue (direction within the equiluminant plane). The saturation losses are largest for test stimuli that lie along the chromatic axis defining the adapting modulation, while the hue changes are rotations away from the adapting direction and toward an orthogonal direction within the S and L-M plane. Similar selective changes in both perceived color and perceived lightness occur following adaptation to stimuli that covary in luminance and chromaticity. The selectivity of the aftereffects for multiple directions within color-luminance space is inconsistent with sensitivity changes in only three independent channels. These aftereffects suggest instead that color appearance depends on channels that can be selectively tuned to any color-luminance direction, and that there are no directions that invariably isolate responses in only a single channel. We use the perceived color changes to examine the spectral sensitivities of the chromatic channels and to estimate the distribution of channels. We also examine how adaptation alters the contrast-response function, how it affects reaction times for luminance and chromatic contrast, the extent to which the aftereffects exhibit interocular transfer, and the way in which the perceived color changes differ from those induced by conventional light adaptation.

Adaptation, Ocular↗

Luminance noise and the rapid determination of discrimination ellipses in colour deficiency.

A computer-controlled test of colour vision is described, in which luminance noise and masking contours are used to ensure that the subject's responses depend on chromatic signals. The test avoids the need--common to most computer-controlled tests--to define equiluminance for the individual subject before the colour test itself can be administered. The test achieves a good separation of protan and deutan subjects and reveals the large range of chromatic sensibilities among anomalous trichromats. As a population, dichromats had higher thresholds on the tritan axis of the test than did normals. In an extension of the test, full discrimination ellipses were measured for normal and colour-deficient observers. The nature of anomalous trichromacy is discussed and the possibility is raised that hybrid genes, resulting from genetic recombination, may code for incorrectly labelled or functionally impaired molecules.

Adolescent↗

Sequence divergence, polymorphism and evolution of the middle-wave and long-wave visual pigment genes of great apes and Old World monkeys.

In man, the spectral shift between the middle-wave (MW) and long-wave (LW) visual pigments is largely achieved by amino acid substitution at two codons, both located in exon 5. A third amino acid site coded by exon 3 is polymorphic between pigments. We have studied the equivalent regions of the cone opsin genes in two members of the Hominidea (the gorilla, Gorilla gorilla and the chimpanzee, Pan troglodytes) and in three members of the Cercopithecoidea family of Old World primates (the diana monkey, Cercopithecus diana, the talapoin monkey, Miopithecus talapoin, and the crab-eating macaque, Macaca fascicularis). No variation in the codons that specify the amino acids involved in spectral tuning were found. We predict therefore that the MW and LW pigments of gorilla and chimpanzee have similar spectral characteristics to those of man. Multiple copies of the same opsin gene sequence were identified in the chimpanzee, talapoin and macaque and we also show that non-human Old World primates are similar to man in showing a bunching of polymorphic sites in exon 3. We discuss the ancestry of the separate MW and LW genes of Old World primates and the equivalent polymorphic gene of the marmoset, a New World primate.

Amino Acid Sequence↗

The Nagel anomaloscope and seasonal variation of colour vision.

In 1948 the German physicist, Manfred Richter, reported that colour vision has a seasonal variation. For four colour-normal subjects, he found a sinusoidal variation in the proportion of red and green required to match a monochromatic yellow, the equation known as the 'Rayleigh match'. In summer, subjects required more red in their mixture. The measurements were made with the Nagel anomaloscope, an instrument introduced in 1907 and which today, essentially unchanged, remains the definitive clinical instrument for classifying the many phenotypic variations in colour vision. The variation that Richter recorded in the red-green ratio was large (three Nagel units), and it now takes on fresh interest because it is comparable in size to the difference in Nagel settings later reported between normal observers of different genetic types. We have been able to replicate Richter's result, but report here that it is almost certainly instrumental: the Nagel anomaloscope proves to be very sensitive to ambient temperature.

Color Perception↗

A study of women heterozygous for colour deficiencies.

We have examined the colour vision of 43 female subjects in the age range 30-59 yr of whom 31 were obligate carriers of various forms of colour deficiency and the rest were women who had no known colour-deficient relatives. In the case of all the carriers we established the phenotypes of their colour-deficient sons. As a group, carriers made significantly more errors on the Ishihara plates and showed enlarged matching ranges on the Nagel anomaloscope, but we could not replicate earlier reports of increased error scores on the Farnsworth-Munsell 100-Hue test or of systematic shifts in Rayleigh match mid-points. We did find that the colour matches of carriers of deuteranomaly were significantly displaced from those of normals in a ratio-matching task in which a mixture of 546 and 600 nm was matched with a mixture of 570 and 690 nm. Owing to X-chromosome inactivation, women who are heterozygous for anomalous trichromacy ought to have at least four types of cone in their retinae and we ask whether this affords them an extra dimension of colour vision, by analogy to New World monkeys where heterozygous females gain trichromacy in a basically dichromatic species. Many carriers of anomalous trichromacy exhibited no evidence for tetrachromacy, in that they accepted large-field Rayleigh matches following a rod bleach and they were unable to set unique matches in our ratio-matching task. However, eight carriers of anomalous trichromacy--and no other subject--refused large-field Rayleigh matches; and we found one carrier of deuteranomaly who was apparently able to make unique matches in the ratio-matching task.

Adult↗

Structure and evolution of the polymorphic photopigment gene of the marmoset.

The marmoset Callithrix jacchus jacchus, is typical of a New World monkey in exhibiting a polymorphism of photopigments in the middlewave to longwave (535-565 nm) region of the spectrum. The single X-linked opsin gene that encodes the protein component of these pigments is present in three allelic forms producing, in marmosets, pigments with maximum sensitivities at about 543, 556 and 563 nm. All male monkeys are dichromats, whereas females may be either dichromats or trichromats. A cDNA sequence corresponding to the 563 form of this gene is reported, together with partial genomic DNA sequences of exons 2, 3, 4 and 5 of all three alleles. The origin of these sequences and their divergence from the middlewave- and longwave-sensitive pigments of man is discussed from both a functional and an evolutionary standpoint.

Amino Acid Sequence↗

Contrast adaptation dissociates different measures of luminous efficiency.

We compared how contrast adaptation influences three alternative measures of luminous efficiency. Subjects judged the lightness, the flicker, or the motion of chromatic sine-wave gratings. Adaptation to gratings with correlated luminance and chromatic contrast strongly biases lightness matches and moderately biases minimum-motion settings for gratings that are counterphased at 1 Hz, but it has little effect on motion or flicker settings for gratings that are counterphased at 15 Hz. These results suggest that different measures of equiluminance tap neural pathways that can have different spectral sensitivities. At low temporal frequencies both perceived lightness and minimum-motion settings appear to depend on channels that do not represent luminance and color independently.

Adaptation, Ocular↗

The spatial arrangement of cones in the primate fovea.

The retinae of Old World primates contain three classes of light-sensitive cone, which exhibit peak absorption in different spectral regions. But how are the different types of cone arranged in the hexagonal mosaic of the fovea? This question has often been answered with artists' impressions, but never with direct measurements. Staining for antibodies specific to the short-wave photopigment has revealed a sparse, semiregular array of cones; but nothing is known about the arrangement of the more numerous long- and middle-wave cones. Are they randomly distributed, with chance aggregations of one type, as Hartridge postulated in these columns nearly 50 years ago? Or do they exhibit a regular alteration, recalling the systematic mosaics seen in some non-mammalian species? Or, conversely, is there positive clumping of particular cone types, as might be expected if local patches of cones were descended from a single precursor cell? We have made direct microspectrophotometric measurements of patches of foveal retina from Old World monkeys, and report here that the distribution of long- and middle-wave cones is locally random. These two cone types are present in almost equal numbers, and not in the ratio of 2:1 that has been postulated for the human fovea.

Animals↗

Dichromats detect colour-camouflaged objects that are not detected by trichromats.

To explain the surprisingly high frequency of congenital red-green colour blindness, the suggestion has been made that dichromats might be at an advantage in breaking certain kinds of colour camouflage. We have compared the performance of dichromats and normal observers in a task in which texture is camouflaged by colour. The texture elements in a target area differed in either orientation or size from the background elements. In one condition, the texture elements were all of the same colour; in the camouflage condition they were randomly coloured red or green. For trichromats, it proved to be more difficult to detect the target region in the camouflage condition, even though colour was completely irrelevant to the task. Dichromats (n = 7) did not show this effect, and indeed performed better than trichromats in the camouflage condition. We conclude that colour can interfere with segregation based upon texture, and that dichromats are less susceptible to such interference.

Color Perception↗

Sequence divergence and copy number of the middle- and long-wave photopigment genes in Old World monkeys.

We have studied the sequence and organization of the genes for the middle-wave (MW) and long-wave (LW) cone photopigment genes in six species of Old World monkeys. Previous studies have shown that the MW and LW pigments of all six species exhibit peak sensitivities near 535 nm and 565 nm, respectively, and thus resemble the equivalent human pigments. In the case of man, the protein components of the MW and LW photopigments differ by 15 amino acids, although only seven of these differences involve non-homologous substitutions and are therefore candidates for a role in spectral tuning. Regions corresponding to exons 4 and 5 of these genes, and including five such candidate sites, were sequenced in the Old World monkeys. In contrast to the equivalent human genes, substitutions were found at two of these sites, position 233 and 309 of the MW gene in all six species. The role of amino acid substitutions in the spectral tuning of these photopigments is discussed. A comparison of the nucleotide sequences of the MW and LW genes provides evidence for sequence homogenization within species; the role of gene conversion in the evolution of these genes is discussed. The close juxtaposition and homology of the MW and LW genes on the X chromosome is thought to underlie the high frequency of colour vision defects in man and the presence in many individuals of extra copies of the MW gene. A study of a group of talapoin (Ceropithecus talapoin) monkeys has revealed a similar numerical polymorphism for this gene to that present in man. In contrast to the situation in man, where the MW and LW genes may contain a shortened first intron, restriction digests of genomic DNA showed that the size of this intron does not differ across the six species of Old World monkeys examined.

Amino Acid Sequence↗