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Vladimir (Vova) Seplyarskiy

@vseplyarskiy.bsky.social

Assistant Professor UTSW; Mutagenesis, Population genetics, Evolution in somatic tissues and on phylogenetic tree

54 Posts128 Follower81 Folgt
Gustavo Valadares Barroso@gvbarroso.bsky.social · 3d ago

Phylogenetic conservation scores have long been used to identify selection targets in the genome. With machine learning, they take a new form and will likely grow in popularity. @apragsdale.bsky.social and I investigate their relationship with mutation rates www.biorxiv.org/content/10.6...

Strong correlations between mutation rates and selective constraint in the human genome?

The 21st century has seen repeated challenges to the premise that de novo mutations occur independently from their fitness effects. So far, these attempts have been dismissed as technical artifacts, r...

biorxiv.org

DeBerardinis Lab at UT Southwestern Medical Center@rjdlab.bsky.social · 2w ago

Pleased to share a new paper with Ling Cai, demonstrating the use of population genomics to identify heterozygous variants in a cobalamin processing gene as a modulator of circulating vitamin B12 levels.

The American Journal of Human Genetics@ajhgnews.bsky.social · 2w ago

🧬New Research Letter! 📄MMACHC burden variants are associated with higher circulating vitamin B12 in the All of Us cohort @rjdlab.bsky.social

Vladimir (Vova) Seplyarskiy@vseplyarskiy.bsky.social · 3w ago

Our department is hiring! www.nature.com/naturecareer... I joined recently and have had a very positive experience. Happy to share more—DM me if you’re considering applying! Only 3 weeks left to apply.

Tenure-Track Faculty Positions in Human Genetics - Dallas, Texas (US) job with The University of Texas Southwestern Medical Center (UT Southwestern Medical Center) | 12862060

Tenure-Track Faculty Positions in Human Genetics

nature.com

Marta Grońska-Pęski@gronskapeski.bsky.social · last mo.

Can dietary interventions change how fast genomes accumulate mutations with age? We studied how caloric restriction (CR)—one of the most robust lifespan-extending interventions—affects somatic mutations across the genome in different tissues and cell types in mice.

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Tom Sasani@tomsasani.bsky.social · last mo.

How long does DNA damage last? @aaronquinlan.bsky.social and I found evidence that lesions are transmitted from parent (P0) to offspring (F1) in C. elegans. If they segregate unrepaired for multiple cell divisions, lesions generate multi-allelism in the F1 germline. www.biorxiv.org/content/10.6...

Inherited DNA damage generates multi-allelic mutations in C. elegans

Exogenous and endogenous mutagens generate a wide variety of DNA lesions, including bulky adducts, chemical modifications, and single- or double-stranded breaks. A phenomenon called “lesion segregation,” in which lesions evade repair and persist for multiple cell divisions, has recently been documented in tumors and healthy somatic tissues from mice and humans, respectively. Persistent lesions can generate multi-allelic variants (MAVs) by serving as templates for multiple rounds of error-prone replication. By reanalyzing data from a large C. elegans mutagenesis experiment, we observed robust evidence for MAVs at a small fraction (∼0.2%) of mutated sites in the offspring of strains treated with alkylating agents. Because these sequencing data were derived from the progeny of a single F1 animal — itself the offspring of a mutagenized P0 — all mutations should be biallelic. The presence of multi-allelic variation implies that some DNA lesions are transmitted to the F1 zygote, evade repair, and are repeatedly bypassed by error-prone polymerases during embryogenesis. We suspect that many more lesions are inherited than is suggested by MAV prevalence, and that a large fraction of biallelic mutations are also caused by inherited lesions. Our results demonstrate that DNA lesions serve as durable, transgenerational templates for mutagenesis in C. elegans . We speculate that lesion segregation in the early embryo may be a source of mosaicism and genetic diversity in humans, as well. ### Competing Interest Statement The authors have declared no competing interest. National Institutes of Health, https://ror.org/01cwqze88, R01HG012252

biorxiv.org

James Gagnon@james-gagnon.bsky.social · 2mo ago

In a new (ish) preprint, we used CRISPR barcodes to label germline stem cell clones in zebrafish, then tracked their contributions to sperm production for 2 years. Instead of staying stable, individual clones rose, fell, and disappeared over time. www.biorxiv.org/content/10.6...

Clonal dynamics deviate from neutral drift in zebrafish spermatogenesis

Spermatogonial stem cells (SSCs) maintain male fertility, but how their clonal dynamics change with age remains poorly understood. Here, we use in vivo CRISPR barcoding in zebrafish to label SSCs and ...

biorxiv.org

David J. Bier@davidjbier.bsky.social · 3mo ago

The most anti-legal immigrant administration ever just made it illegal for international students to transfer schools or change majors or shift any "educational objective" in their 1st year and for graduate students **at any point** ever, at all. There is no legal basis for this

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Vladimir (Vova) Seplyarskiy@vseplyarskiy.bsky.social · 4mo ago

Very happy with study spearheaded by Prathitha. One highlight for me. Building on idea from elifesciences.org/articles/71513 we showed that it is possible to detect selection for individual missense mutations in hypermutable sites.

Mutation saturation for fitness effects at human CpG sites

Methylated CpG sites are saturated for T mutations in a sample of 390K human exomes, providing a test case for inferences about fitness effects in human genes, and insight into the interpretation of m...

elifesciences.org

Pprathitha.bsky.social@prathitha.bsky.social · 4mo ago

Excited to share our new preprint, "Inference of elevated mutation rates and variant effects using 700k exomes"! - www.biorxiv.org/content/10.6... Using gnomAD v4, we estimate per-variant missense selection coefficients, and find loss-of-function (LoF) mutations with enhanced mutation rates.

Dan Landau@landau.bsky.social · 4mo ago

New results with tree reconstruction of glioma progression. Phylodynamics applied to primary patient samples allow to define how progression is linked to changes in differentiation hierarchies. We ❤️ trees!

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Masashi Nomura@masashi-nomura.bsky.social · 4mo ago

1/12 Excited to share that our new paper on IDH-mutant glioma (IDH-G) is now out in Nature Genetics! This work was a fantastic collaborativ effort of laboratories of @suvalab.bsky.social and @landau.bsky.social, co-lead by Ramya Raviram and Joshua S. Schiffman. www.nature.com/articles/s41...

Dmitri Petrov@petrovadmitri.bsky.social · 4mo ago

Very pleased with the response and still have spots & funding especially for students/postdocs. Sign up soon before it gets full. If you are working at or wanting to learn about the intersection of functional biology and ecology/evolution, you would get a lot of it! www.grc.org/function-of-...

Function of Evolving Systems - Gordon Research Conferences

GRC presents Function of Evolving Systems, a conference on .

grc.org

Kamila Naxerova@naxerova.bsky.social · 4mo ago

Please join us in NH (perfect place to be in August!) for this inspiring conference organized by @petrovadmitri.bsky.social and Joy Bergelson. Very interdisciplinary, so I look forward to learning tons of new concepts. www.grc.org/function-of-...

Molly Przeworski@mollyprz.bsky.social · 4mo ago

Now published: journals.plos.org/plosbiology/...

What sets the mutation rate of a cell type in an animal species?

Mutation rates per generation are strikingly similar across germlines of animals and across at least one somatic cell type, suggesting a key role for natural selection in shaping mutation rates. This ...

journals.plos.org

Molly Przeworski@mollyprz.bsky.social · 10mo ago

Happy to highlight an essay I wrote together with @marcdemanuel.bsky.social, @natanaels.bsky.social and Anastasia Stolyarova, trying to think through what sets the mutation rate of a cell type in an animal species: www.biorxiv.org/content/10.6... 1/n

Molly Przeworski@mollyprz.bsky.social · 5mo ago

Happy to highlight new findings by Vanesa Getseva and Lin Poyraz about the sources of variation in germline mutation rates among humans: www.biorxiv.org/content/10.6... Joint work with Anastasia Stolyarova and @ipsitaagarwal.bsky.social. 1/n

A sibling study of variation in parental mutation rates

People are born with variable numbers of de novo germline mutations (DNMs), depending primarily on the ages of their parents. To explore additional causes, we developed an approach to call DNMs from nucleotide differences between siblings in genomic regions inherited identical by descent from both parents. Applying it to whole genome sequences from 28,985 sibling pairs of diverse genetic ancestries present in the UK Biobank and All of Us datasets, as well as 2,330 trios, we identified >800K autosomal DNMs and characterized mutation phenotypes in 27,645 sets of parents. We found subtle shifts in the mutation spectrum but no differences in total DNM rates among genetic ancestry groups, or between smokers and non-smokers. Testing for associations between parental mutation phenotypes and their burden of loss-of-function and deleterious missense variants in a set of 180 DNA repair and maintenance genes, we discovered that disruptions in REV1 and LIG1 increase germline mutation rates, and thus that rare mutator alleles segregate in population cohorts. ### Competing Interest Statement The authors have declared no competing interest. NIH, R35 GM083098

biorxiv.org