Showing papers by "Dennis P. Wall published in 2005"

Functional genomic analysis of the rates of protein evolution

Abstract: The evolutionary rates of proteins vary over several orders of magnitude. Recent work suggests that analysis of large data sets of evolutionary rates in conjunction with the results from high-throughput functional genomic experiments can identify the factors that cause proteins to evolve at such dramatically different rates. To this end, we estimated the evolutionary rates of >3,000 proteins in four species of the yeast genus Saccharomyces and investigated their relationship with levels of expression and protein dispensability. Each protein's dispensability was estimated by the growth rate of mutants deficient for the protein. Our analyses of these improved evolutionary and functional genomic data sets yield three main results. First, dispensability and expression have independent, significant effects on the rate of protein evolution. Second, measurements of expression levels in the laboratory can be used to filter data sets of dispensability estimates, removing variates that are unlikely to reflect real biological effects. Third, structural equation models show that although we may reasonably infer that dispensability and expression have significant effects on protein evolutionary rate, we cannot yet accurately estimate the relative strengths of these effects. protein dispensability protein fitness structural equation models

Adjusting for Selection on Synonymous Sites in Estimates of Evolutionary Distance

Abstract: Evolution at silent sites is often used to estimate the pace of selectively neutral processes or to infer differences in divergence times of genes. However, silent sites are subject to selection in favor of preferred codons, and the strength of such selection varies dramatically across genes. Here, we use the relationship between codon bias and synonymous divergence observed in four species of the genus Saccharomyces to provide a simple correction for selection on silent sites.

Origin and rapid diversification of a tropical moss.

Abstract: Molecular sequences rarely evolve at a constant rate. Yet, even in instances where a clock can be assumed or approximated for a particular set of sequences, fossils or clear patterns of vicariance are rarely available to calibrate the clock. Thus, obtaining absolute timing for diversification of natural lineages can prove difficult. Unfortunately, without absolute time we cannot develop a complete understanding of important evolutionary processes, including adaptive radiations and key innovations. In the present study, the coding sequence of the nuclear gene, glyceraldehyde 3-phosphate dehydrogenase (gpd), extracted from the paleotropical moss, Mitthyridium, was found to exhibit clocklike behavior and used to reconstruct the history of 80 distinct molecular lineages that cover the full geographic range of Mitthyridium. Two separate clades endemic to two geographically distinct oceanic archipelagos were revealed by this phylogenetic analysis. This allowed the use of island age (as derived from potassium-argon dating) as a maximum age of origin of each monophyletic group, providing two independent time anchors for the clock found in gpd, the final piece needed to study absolute time. Based on results from both maximum age calibrations, which separately yielded highly consistent estimates, the ancestor of this moss group arose approximately 8 million years ago, and then diversified at the rapid rate of 0.56 ± 0.004 new lineages per million years. Such a rate is on par with the highest diversification rates reported in the literature including rapidly radiating insular groups like the Hawaiian silversword alliance, a classic example of an adaptive radiation. Using independent sources of data, it was found that neither the age nor diversification estimates were affected by the use of molecular lineages rather than species as the operational taxonomic units. Identifying the cause for this rapid diversification requires further testing, but it appears to be related to a general shift in reproductive strategy from sexual to asexual, which may be a key innovation for this young group.

Conservation of the RB1 gene in human and primates

Abstract: Mutations in the RB1 gene are associated with retinoblastoma, which has served as an important model for understanding hereditary predisposition to cancer. Despite the great scrutiny that RB1 has enjoyed as the prototypical tumor suppressor gene, it has never been the object of a comprehensive survey of sequence variation in diverse human populations and primates. Therefore, we analyzed the coding (2,787 bp) and adjacent intronic and untranslated (7,313 bp) sequences of RB1 in 137 individuals from a wide range of ethnicities, including 19 Asian Indian hereditary retinoblastoma cases, and five primate species. Aside from nine apparently disease-associated mutations, 52 variants were identified. They included six singleton, coding variants that comprised five amino acid replacements and one silent site. Nucleotide diversity of the coding region (pi=0.0763+/-1.35 x 10(-4)) was 52 times lower than that of the noncoding regions (pi=3.93+/-5.26 x 10(-4)), indicative of significant sequence conservation. The occurrence of purifying selection was corroborated by phylogeny-based maximum likelihood analysis of the RB1 sequences of human and five primates, which yielded an estimated ratio of replacement to silent substitutions (omega) of 0.095 across all lineages. RB1 displayed extensive linkage disequilibrium over 174 kb, and only four unique recombination events, two in Africa and one each in Europe and Southwest Asia, were observed. Using a parsimony approach, 15 haplotypes could be inferred. Ten were found in Africa, though only 12.4% of the 274 chromosomes screened were of African origin. In non-Africans, a single haplotype accounted for from 63 to 84% of all chromosomes, most likely the consequence of natural selection and a significant bottleneck in effective population size during the colonization of the non-African continents.