bioRxiv Science⌕ Search

Biology subjects

Levinstein Hallak, K.

Publications and source records attributed to Levinstein Hallak, K..

2 recordsLinked to original sources

Dating ancient humans splits by estimating Poisson rates from mitochondrial DNA parity samples

We tackle the problem of estimating species divergence times, given a genome sequence from each species and a large known phylogenetic tree with a known structure (typically from one of the species). The number of transitions at each site from the first sequence to the other is assumed to be Poisson distributed, and only the parity of the number of transitions is observed. The detailed phylogenetic tree contains information about the transition rates in each site. We use this formulation to develop and analyze multiple estimators of the divergence between the species. To test our methods, we use mtDNA substitution statistics from the well-established Phylotree as a baseline for data simulation such that the substitution rate per site mimics the real-world observed rates. We evaluate our methods using simulated data and compare them to the Bayesian optimizing software BEAST2, showing that our proposed estimators are accurate for a wide range of divergence times and significantly outperform BEAST2. We then apply the proposed estimators on Neanderthal, Denisovan, and Chimpanzee mtDNA genomes to better estimate their TMRCA (Time to Most Recent Common Ancestor) with modern humans and find that their TMRCA is sub-stantially later, compared to values cited recently in the literature.

evolutionary biology↗

Big data analysis of mitochondrial DNA substitution models: A regression approach elucidating the effects of codon position and neighboring nucleotides

We build on the up-to-date version of Phylotree, a comprehensive and continuously updating phylogeny of global human mtDNA variations (van Oven and Kayser 2009), to better understand the substitution mechanism of the mitochondrial DNA (mtDNA) and its most influential factors. We do so by composing Poisson and negative-binomial regression models relating the rate of occurrence of mtDNA substitutions to various factors. Important factors we identify include the identity of the codon at each position, confirming previous findings about the biological significance of different codons for the same amino acid. Importantly, we also identify a significant effect of neighboring sites. This effect cannot be attributed solely to CpG pairs. A similar effect of neighboring sites was recently described for autosomal DNA substitutions, and we speculate it is related to the basic mutational mechanism itself. Once codon composition and context are taken into account, there is no significant difference in substitution rate between different genes in mtDNA.

evolutionary biology↗