Biomedical subjects

Soojin V Yi

Publications and source records attributed to Soojin V Yi.

6 recordsLinked to original sources

PubMed2021

Evolution of DNA methylation in the human brain.

DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.

Animals↗

PubMed2006

Understanding relationship between sequence and functional evolution in yeast proteins.

The underlying relationship between functional variables and sequence evolutionary rates is often assessed by partial correlation analysis. However, this strategy is impeded by the difficulty of conducting meaningful statistical analysis using noisy biological data. A recent study suggested that the partial correlation analysis is misleading when data is noisy and that the principal component regression analysis is a better tool to analyze biological data. In this paper, we evaluate how these two statistical tools (partial correlation and principal component regression) perform when data are noisy. Contrary to the earlier conclusion, we found that these two tools perform comparably in most cases. Furthermore, when there is more than one 'true' independent variable, partial correlation analysis delivers a better representation of the data. Employing both tools may provide a more complete and complementary representation of the real data. In this light, and with new analyses, we suggest that protein length and gene dispensability play significant, independent roles in yeast protein evolution.

Evolution, Molecular↗

PubMed2006

Heterogeneous genomic molecular clocks in primates.

Using data from primates, we show that molecular clocks in sites that have been part of a CpG dinucleotide in recent past (CpG sites) and non-CpG sites are of markedly different nature, reflecting differences in their molecular origins. Notably, single nucleotide substitutions at non-CpG sites show clear generation-time dependency, indicating that most of these substitutions occur by errors during DNA replication. On the other hand, substitutions at CpG sites occur relatively constantly over time, as expected from their primary origin due to methylation. Therefore, molecular clocks are heterogeneous even within a genome. Furthermore, we propose that varying frequencies of CpG dinucleotides in different genomic regions may have contributed significantly to conflicting earlier results on rate constancy of mammalian molecular clock. Our conclusion that different regions of genomes follow different molecular clocks should be considered when inferring divergence times using molecular data and in phylogenetic analysis.

Animals↗

PubMed2006

Correlated asymmetry of sequence and functional divergence between duplicate proteins of Saccharomyces cerevisiae.

The role of sequence divergence in functional divergence of duplicate genes is a topic of great interest. In this study, we compare the numbers of amino acid substitutions in each sequence since two yeast duplicates diverged, using a preduplication ancestral outgroup. Using this strategy, we explored the relationship between sequence divergence and functional divergence between duplicate partners. We show that the degree of relative functional asymmetry between duplicate proteins is proportional to the relative sequence divergence between them. Furthermore, of the two duplicates, the copy closer to their ancestral sequence (fewer number of amino acid substitutions) interacts with more proteins and affects fitness more severely when deleted. Therefore, asymmetric sequence divergence between duplicates is correlated with asymmetric functional divergence and may underlie the duplicate's role in genetic robustness against mutations. Among the functional traits considered, protein abundance appears to have the strongest correlation with the nonsynonymous divergence between duplicates. Taken together with the results from whole-genome analyses, our results indicate that within-species duplicates are subject to the same evolutionary force that acts on interspecific sequence and functional divergence. In particular, we detect signs of purifying selection on the more slowly evolving duplicate.

Amino Acids↗

PubMed2006

Variable molecular clocks in hominoids.

Generation time is an important determinant of a neutral molecular clock. There are several human-specific life history traits that led to a substantially longer generation time in humans than in other hominoids. Indeed, a long generation time is considered an important trait that distinguishes humans from their closest relatives. Therefore, humans may exhibit a significantly slower molecular clock as compared to other hominoids. To investigate this hypothesis, we performed a large-scale analysis of lineage-specific rates of single-nucleotide substitutions among hominoids. We found that humans indeed exhibit a significant slowdown of molecular evolution compared to chimpanzees and other hominoids. However, the amount of fixed differences between humans and chimpanzees appears extremely small, suggesting a very recent evolution of human-specific life history traits. Notably, chimpanzees also exhibit a slower rate of molecular evolution compared to gorillas and orangutans in the regions analyzed.

Animals↗

PubMed2006

Non-adaptive evolution of genome complexity.

Genome complexity is correlated with biological complexity. A recent paper by Michael Lynch proposes that evolution of complex genomic architecture was driven primarily by non-adaptive stochastic forces, rather than by adaptive evolution.1 A general negative relationship between selection efficiency and genome complexity provides a strong support for this hypothesis. The broad capacity of this theory is both its appeal and source for criticism.

Biological Evolution↗