Biomedical subjects

Eliot C Bush

Publications and source records attributed to Eliot C Bush.

8 recordsLinked to original sources

PubMed2006

The evolution of word composition in metazoan promoter sequence.

The field of molecular evolution provides many examples of the principle that molecular differences between species contain information about evolutionary history. One surprising case can be found in the frequency of short words in DNA: more closely related species have more similar word compositions. Interest in this has often focused on its utility in deducing phylogenetic relationships. However, it is also of interest because of the opportunity it provides for studying the evolution of genome function. Word-frequency differences between species change too slowly to be purely the result of random mutational drift. Rather, their slow pattern of change reflects the direct or indirect action of purifying selection and the presence of functional constraints. Many such constraints are likely to exist, and an important challenge is to distinguish them. Here we develop a method to do so by isolating the effects acting at different word sizes. We apply our method to 2-, 4-, and 8-base-pair (bp) words across several classes of noncoding sequence. Our major result is that similarities in 8-bp word frequencies scale with evolutionary time for regions immediately upstream of genes. This association is present although weaker in intronic sequence, but cannot be detected in intergenic sequence using our method. In contrast, 2-bp and 4-bp word frequencies scale with time in all classes of noncoding sequence. These results suggest that different genomic processes are involved at different word sizes. The pattern in 2-bp and 4-bp words may be due to evolutionary changes in processes such as DNA replication and repair, as has been suggested before. The pattern in 8-bp words may reflect evolutionary changes in gene-regulatory machinery, such as changes in the frequencies of transcription-factor binding sites, or in the affinity of transcription factors for particular sequences.

Amino Acids↗

PubMed2005

Selective constraint on noncoding regions of hominid genomes.

An important challenge for human evolutionary biology is to understand the genetic basis of human-chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids.

Animals↗

PubMed2005

Different classes of tissue-specific genes show different levels of noncoding conservation.

We divide tissue-specific genes into two major classes: regulators, defined as genes participating in tissue-specific transcriptional regulation, and effectors, defined as genes involved in rendering the physiological properties of cells. We show that regulators tend to have significantly greater noncoding conservation than effectors. We further show that within the regulator class, tissue-specific transcription factors generally have the greatest noncoding conservation, whereas signal receptors generally have the least noncoding conservation. Using noncoding conservation as a proxy for the complexity of cis-regulatory DNA, we extrapolate that different classes of tissue-specific genes tend to have different levels of cis-regulatory complexity and that greater complexity can be found in genes involved in transcriptional regulation, especially transcription factors.

Animals↗

PubMed2004

The scaling of frontal cortex in primates and carnivores.

Size has a profound effect on the structure of the brain. Many brain structures scale allometrically, that is, their relative size changes systematically as a function of brain size. Here we use independent contrasts analysis to examine the scaling of frontal cortex in 43 species of mammals including 25 primates and 15 carnivores. We find evidence for significant differences in scaling between primates and carnivores. Primate frontal cortex hyperscales relative to the rest of neocortex and the rest of the brain. The slope of frontal cortex contrasts on rest of cortex contrasts is 1.18 (95% confidence interval, 1.06-1.30) for primates, which is significantly greater than isometric. It is also significantly greater than the carnivore value of 0.94 (95% confidence interval, 0.82-1.07). This finding supports the idea that there are substantial differences in frontal cortex structure and development between the two groups.

Animals↗

PubMed2004

High-resolution computed tomography study of the cranium of a fossil anthropoid primate, Parapithecus grangeri: new insights into the evolutionary history of primate sensory systems.

Extant anthropoids have large brains, small olfactory bulbs, and high-acuity vision compared with other primates. The relative timing of the evolution of these characteristics may have important implications for brain evolution. Here computed tomography is used to examine the cranium of a fossil anthropoid, Parapithecus grangeri. It is found that P. grangeri had a relatively small brain compared with living primates. In addition, it had an olfactory bulb in the middle of the range for living primates. Methods for relating optic foramen area and other cranial measurements to acuity are discussed. Multiple regression is used to estimate retinal ganglion cell number in P. grangeri. Given currently available comparative data, P. grangeri seems to have had retinal ganglion cell counts intermediate for living primates, overlapping with the upper end of the range for strepsirrhines and possibly with the lower end for anthropoids.

Animals↗

PubMed2004

Three-dimensional structure and evolution of primate primary visual cortex.

In this study, three-dimensional reconstructions of primate primary visual cortex (V1) were used to address questions about its evolution. The three-dimensional shape of V1 in anthropoids is significantly longer and narrower than in strepsirrhines. This difference is an effect of clade and is not due to differences in activity pattern or V1 size. New measurements of V1 volume were also provided in order to reassess V1 size differences between strepsirrhines and anthropoids. It was found that for a given lateral geniculate nucleus (LGN) volume, anthropoids have a significantly larger V1 than strepsirrhines do. This is important since LGN is the principal source of V1's input. Finally, independent contrasts analysis was used to examine the scaling of V1 relative to LGN, the rest of cortex, and the rest of the brain. It was confirmed that V1 scales with positive allometry relative to LGN. A number of possible explanations for scaling are discussed. V1 scaling may have to do with the tendency of large brains to be more compartmentalized than small brains, or V1 scaling might reflect the geometry of information representation.

Animals↗

PubMed2003

The scaling of white matter to gray matter in cerebellum and neocortex.

It is known that the white matter of neocortex increases disproportionately with brain size. However, relatively few measurements have been made of white matter/gray matter scaling in the cerebellum. We present data on the volumes of white and gray matter in both structures, taken from 45 species of mammals. We find a scaling exponent of 1.13 for cerebellum and 1.28 for neocortex. The 95% confidence intervals for our estimates of these two exponents do not overlap. This difference likely reflects differences in the connectivity and/or micro-structure of white matter in the two regions.

Animals↗

PubMed2002

Rapid long lasting learning in a collinear edge-detection task.

We have developed a detection task in which subjects identify a pair of collinear edges in a field of polygons. Five of our six subjects showed significant, rapid learning at this task. Four showed evidence of retention a day and a week later. In several transfer tests, we found that disruption of the distractors produced a significant drop-off in performance. These results are consistent with a model in which collinear targets initially produce a salience signal too weak to be reliably detected over the noise of the distractors. As the experiment proceeds, the visual system learns to dampen the distractor signals, allowing for more reliable detection.

Adult↗