Browsing by Author "Leu, Jun-Yi"

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Clusters of Nucleotide Substitutions and Insertion/Deletion Mutations Are Associated with Repeat Sequences
(2011-06-01)
McDonald, Michael J.
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Wang, Wei-Chi
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Huang, Hsien-Da
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Leu, Jun-Yi
;
生物科技學系
The genome-sequencing gold rush has facilitated the use of comparative genomics to uncover patterns of genome evolution, although their causal mechanisms remain elusive. One such trend, ubiquitous to prokarya and eukarya, is the association of insertion/deletion mutations (indels) with increases in the nucleotide substitution rate extending over hundreds of base pairs. The prevailing hypothesis is that indels are themselves mutagenic agents. Here, we employ population genomics data from Escherichia coli, Saccharomyces paradoxus, and Drosophila to provide evidence suggesting that it is not the indels per se but the sequence in which indels occur that causes the accumulation of nucleotide substitutions. We found that about two-thirds of indels are closely associated with repeat sequences and that repeat sequence abundance could be used to identify regions of elevated sequence diversity, independently of indels. Moreover, the mutational signature of indel-proximal nucleotide substitutions matches that of error-prone DNA polymerases. We propose that repeat sequences promote an increased probability of replication fork arrest, causing the persistent recruitment of error-prone DNA polymerases to specific sequence regions over evolutionary time scales. Experimental measures of the mutation rates of engineered DNA sequences and analyses of experimentally obtained collections of spontaneous mutations provide molecular evidence supporting our hypothesis. This study uncovers a new role for repeat sequences in genome evolution and provides an explanation of how fine-scale sequence contextual effects influence mutation rates and thereby evolution.
The evolutionary dynamics of tRNA-gene copy number and codon-use in E-coli
(2015-08-19)
McDonald, Michael J.
;
Chou, Chih-Hung
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Swamy, Krishna B. S.
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Huang, Hsien-Da
;
Leu, Jun-Yi
Background: The introduction of foreign DNA by Lateral Gene Transfer (LGT) can quickly and drastically alter genome composition. Problems can arise if the genes introduced by LGT use codons that are not suited to the host's translational machinery. Here we investigate compensatory adaptation of E. coli in response to the introduction of large volumes of codons that are rarely used by the host genome. Results: We analyze genome sequences from the E. coli/Shigella complex, and find that certain tRNA genes are present in multiple copies in two pathogenic Shigella and O157:H7 subgroups of E. coli. Furthermore, we show that the codons that correspond to these multi-copy number tRNA genes are enriched in the high copy number Selfish Genetic Elements (SGE's) in Shigella and laterally introduced genes in O157:H7. We analyze the duplicate copies and find evidence for the selective retention of tRNA genes introduced by LGT in response to the changed codon content of the genome. Conclusion: These data support a model where the relatively rapid influx of LGT genes and SGE's introduces a large number of genes maladapted to the host's translational machinery. Under these conditions, it becomes advantageous for the host to retain tRNA genes that are required for the incorporation of amino acids at these codons. Subsequently, the increased number of copies of these specific tRNA genes adjusts the cellular tRNA pool to the demands set by global shifts in codon usage.