Molly Przeworski @molly_przew Twitter profile

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Molly Przeworski

@molly_przew

2 months

Stream or attend a conference on Frontiers in Human Genetics at Columbia University (Oct 10 & 11), by registering here:

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Molly Przeworski

@molly_przew

11 months

The @eLife board has decided to fire the editor-in-chief for expressing his personal political opinion, in this case his concern about the bombing of civilians.

Michael Eisen

@mbeisen

11 months

I have been informed that I am being replaced as the Editor in Chief of @eLife for retweeting a @TheOnion piece that calls out indifference to the lives of Palestinian civilians.

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Molly Przeworski

@molly_przew

11 months

I have therefore made the unhappy decision to resign as senior editor at @eLife , after ten years working for the journal.

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Molly Przeworski

@molly_przew

11 months

This decision is both discriminatory and a dangerous precedent; it is also a violation of @eLife ’s own code of conduct, to be "respectful of differing opinions, viewpoints, and experiences.”

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Molly Przeworski

@molly_przew

3 years

I keep reading versions of the statement that genetic differences within a human population have no implications for genetic differences between populations, alongside strong statements about what we know about the causes of differences within a population. 1/n

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Molly Przeworski

@molly_przew

5 years

Everything you have ever wanted to know about evolutionary quantitative genetics and GWAS but were afraid to ask, by Guy Sella and Nick Barton

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Molly Przeworski

@molly_przew

2 years

Congratulations to Deborah Charlesworth for her election to the National Academy of Sciences. Long, long overdue.

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Molly Przeworski

@molly_przew

3 years

Hiring a postdoc with a strong statistical or computational background, interested in polygenic scores, their interpretation and their generalizability. Email me if interested. Starting date flexible but can be immediate. Thanks in advance for RT.

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Molly Przeworski

@molly_przew

6 years

Wonderful collaboration with @ziyue_gao @moorjani_priya & @GuyAmster on human germline mutation. Our surprising findings: 1/4

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Molly Przeworski

@molly_przew

4 years

I am looking to hire a postdoc at Columbia U., for a project modeling mutation processes. Applicants must have a strong quantitative background (in theoretical pop. gen., statistics or applied math/physics). Starting date flexible. If interested, email me. Grateful for RT.

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Molly Przeworski

@molly_przew

3 years

Hiring a postdoc with quantitative training and an interest in population genetics & evolution. Many possible topics. More about the lab here: If potentially interested, email me. Thanks for RT.

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Molly Przeworski

@molly_przew

3 years

Cool experimental results on patterns of mutation accumulation in human somatic tissues: Abascal et al. find a linear increase of mutations with time in post-mitotic neurons and “similar rates and signatures to some mitotically active tissues” 1/n

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Molly Przeworski

@molly_przew

3 years

But most of the time, we don’t mean something all that precise. As the quip goes “An academic discipline is a set of individuals who agree not to question the same assumption” For population genetics, that assumption is a population. 6/n

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Molly Przeworski

@molly_przew

2 years

In many contexts in human genetics, it is useful to know how deleterious the loss of a gene copy is likely to be. Hence the many, widely-used genic measures of “intolerance to mutation”.

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Molly Przeworski

@molly_przew

1 year

A thread about how meiotic recombination is directed to the genome in vertebrates and what Carla Hoge, @MarcdeManuel & co-authors discovered about it by studying corn snakes. 1/n

Patterns of recombination in snakes reveal a tug of war between PRDM9 and promoter-like features

In vertebrates, there are two known mechanisms by which meiotic recombination is directed to the genome: in humans, mice, and other mammals, recombination occurs almost exclusively where the protein...

www.biorxiv.org

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Molly Przeworski

@molly_przew

7 months

I have been following the discussion around how best to represent and label human genetic variation, and thought it might also be worth discussing an aspect of the broader context. 1/n

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Molly Przeworski

@molly_przew

3 years

Delighted to highlight new work by @izabelcavassim and @ZachTWBaker , on the evolution and co-evolution of PRDM9 in vertebrates: 1/n

PRDM9 losses in vertebrates are coupled to the loss of at least three other meiotic genes

In most mammals and likely throughout vertebrates, the gene PRDM9 specifies the locations of meiotic double strand breaks; in mice and humans at least, it also aids in their repair. For both roles,...

www.biorxiv.org

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Molly Przeworski

@molly_przew

3 years

So a population is a convenient abstraction that can obscure a key issue: When interpreting trait differences, we are forced to make comparisons among humans who experience different sets of environments without being able to control for them well. 25/25

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Molly Przeworski

@molly_przew

3 years

I think there may be a miscommunication here

Grey Monroe

@Grey_Monroe

3 years

"A fundamental tenet of evolutionary biology is that mutations are random events...the likelihood of any particular mutational event is independent of its specific value to the organism" Lenski & Mittler, 1993

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Molly Przeworski

@molly_przew

2 years

Over the past decade, it has become clear that different types of germline mutations accumulate with maternal and paternal ages at somewhat different rates, see, e.g.,

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Molly Przeworski

@molly_przew

3 years

In the real world, the distinction between “within” and “between” populations is illusory. There is a giant family tree of humanity, and people who share more ancestral paths through it than others, and more similar environments than others. 7/n

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Molly Przeworski

@molly_przew

7 years

Immensely happy news: my former postdoc Molly Schumer will be joining the Biology faculty at Stanford.

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Molly Przeworski

@molly_przew

6 months

For those in the NY area, SAVE THE DATE (& register) for a Symposium on Human Genetics at Columbia University: Oct 10-11 2024. Talks will also be streamed.

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Molly Przeworski

@molly_przew

5 years

To date, most of the discussion about polygenic scores has focused on differences (allele frequencies, LD) driven by population structure and implicitly reduced the question of portability to a population genetics problem.

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Molly Przeworski

@molly_przew

6 years

Now published, @yuvalsim and Guy Sella's treatise: from the ground up, how to interpret GWAS findings and differences among traits

A population genetic interpretation of GWAS findings for human quantitative traits

Author summary One of the central goals of evolutionary genetics is to understand the processes that give rise to phenotypic variation in humans and other taxa. Genome-wide association studies...

journals.plos.org

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Molly Przeworski

@molly_przew

6 years

@bvhalldorsson @moorjani_priya Hey @bvhalldorsson @sciencemagazine , this is not consistent with what is stated in the paper "The crossover and DNM data used in this work are available in the supplementary materials."

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Molly Przeworski

@molly_przew

3 years

But none of these observations make mutation non-random *with regard to the outcome*, which is what these quotes are about.

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Molly Przeworski

@molly_przew

5 years

Privileged and delighted to announce on @ziyue_gao Ziyue Gao’s behalf that she will be joining the Genetics faculty at UPenn as of May 2020.

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Molly Przeworski

@molly_przew

2 years

Along with co-organizers @asiepel and Carolin Kosiol, delighted to announce that #probGen23 , the eighth meeting on Probabilistic Modeling in Genomics, will be held March 8-11 2023 at the Cold Spring Harbor labs.

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Molly Przeworski

@molly_przew

5 years

Felix Wu's work comparing sex-specific germline mutation rates in baboons to humans:

A comparison of humans and baboons suggests germline mutation rates do not track cell divisions

In humans, most germline mutations are inherited from the father. This observation is widely interpreted as resulting from the replication errors that accrue during spermatogenesis. If so, the male...

www.biorxiv.org

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Molly Przeworski

@molly_przew

3 years

It got me thinking about how that distinction is not well defined, for many reasons: principally because (i) “populations” are an abstraction and not a real thing and (ii) that abstraction hides huge amounts of environmental variability… 2/n

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Molly Przeworski

@molly_przew

3 years

Without controlled environments or experiments, heritability estimates are not informative about causes of trait variation, as Lewontin pointed out long ago: 22/n

Annotation: the analysis of variance and the analysis of causes.

www.ncbi.nlm.nih.gov

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Molly Przeworski

@molly_przew

3 years

A thread on @iagarwal2 ’s new preprint “Mutation saturation for fitness effects at human CpG sites”: 1/n

Mutation saturation for fitness effects at human CpG sites

Whole exome sequences have now been collected for millions of humans, with the related goals of identifying pathogenic mutations in patients and establishing reference repositories of data from...

www.biorxiv.org

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Molly Przeworski

@molly_przew

5 years

Hiring a postdoc in population genetics: . If interested, email me, or come find me at Biology of Genomes?

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Molly Przeworski

@molly_przew

3 years

Ipsita Agarwal’s @iagarwal2 doctoral work on the fitness effects of de novo mutations in humans is now out in eLife:

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...

elifesciences.org

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Molly Przeworski

@molly_przew

6 years

New work by Ipsita Agarwal: She uses rare variants in GnomAD as proxies for de novo mutations and different “compartments” of human X and autosome to tease apart the factors (biochemical, life history) that shape the mutation spectrum. 1/n

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Molly Przeworski

@molly_przew

1 year

Congratulations to @mstephens999 , a wonderful colleague, and now a Royal Society Fellow...

Exceptional scientists elected as Fellows of the Royal Society | Royal Society

Eighty exceptional scientists have been elected as Fellows of the Royal Society.

royalsociety.org

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Molly Przeworski

@molly_przew

3 years

These considerations motivate the recent turn from a standard GWAS--which picks up indirect effects, assortative mating, and population stratification effects—back to family designs: . 17/n

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Molly Przeworski

@molly_przew

6 years

A population genetics perspective on measures of "intolerance to mutation" used in human genetics: . Work with @zl_fuller @JeremyJBerg @Hakha_Most and Guy Sella.

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Molly Przeworski

@molly_przew

3 years

So it’s not about whether comparisons are made within vs between hypothetical populations. It’s about all the confounders that exist in the absence of the ability to do experiments and how well we can measure and control for them. 16/n

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Molly Przeworski

@molly_przew

9 months

Registration now open for #Probgen24 , to be held in Vienna April 10-12th 2024. Deadline for a talk or poster: February 15, 2024. See:

Probabilistic Modeling in Genomics 2024

Register below for ProbGen 2024! Registration deadline: March 15, 2024The registration fee must be paid by credit card and includes access to the scientific sessions and all meals at the conference...

events.vbc.ac.at

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Molly Przeworski

@molly_przew

7 years

Delighted for Priya Moorjani, who will leave my group to join the faculty of MCB at UCBerkeley Jan 2018.

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Molly Przeworski

@molly_przew

3 years

and it is therefore misleading to imply there is a qualitative difference between ‘within-population’ and ‘between-population’ comparisons…” 9/n

Population Genetics: Why structure matters

Great care is needed when interpreting claims about the genetic basis of human variation based on data from genome-wide association studies.

elifesciences.org

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Molly Przeworski

@molly_przew

7 years

Biological Sciences at Columbia U. is hiring an Assistant Professor in Genomics: Please RT.

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Molly Przeworski

@molly_przew

1 year

Reading @chrishwiggins & Matthew Jones' How Data Happened & liked their succinct statement: "Few scientific claims should be viewed with more suspicion than claims to innate difference that just happen to reflect our current social arrangements."

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Molly Przeworski

@molly_przew

3 years

We can try slicing and dicing it into bins, but in fact, as @magnusnordborg writes: “Natural populations are never homogeneous, … 8/n

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Molly Przeworski

@molly_przew

3 years

And between-group comparisons are often hopelessly confounded by these environmental differences. 11/n

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Molly Przeworski

@molly_przew

6 years

We find that the ratio of paternal to maternal mutations is already ~3:1 by puberty and remains stable with increasing parental ages => spermatogenesis does not underlie the male bias in human mutation 2/4

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Molly Przeworski

@molly_przew

3 years

Critically, however, the limits imposed by not controlling environmental effects also apply to comparisons among individuals within the study group, not just between groups. Hence the problem of environmental confounding in GWAS: 15/n

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Molly Przeworski

@molly_przew

5 years

Congratulations to Dr. Hakhamanesh Mostafavi @Hakha_Most and best of luck at Stanford and beyond. Very sad to see him leave...

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Molly Przeworski

@molly_przew

3 years

Since humans are never compared in an experimental setting, nothing ensures that environmental effects are identical across groups. 14/n

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Molly Przeworski

@molly_przew

3 years

...that correlate in unknown ways with genetic ancestry. Also bc (iii) it’s often unclear if people are talking about direct genetic effects only, or all the signals that can be picked up in a genome-wide association study (GWAS) 3/n

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Molly Przeworski

@molly_przew

3 years

What people often mean to emphasize, I think, when they make the distinction “within” vs “between population” is something different: It’s that learning about genetic effects on human traits is incredibly difficult, because humans grow up & live in distinct environments. 10/n

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Molly Przeworski

@molly_przew

3 years

It's well known that there are many modifiers of mutation rates, including methylation levels, replication timing and transcription rates.

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Molly Przeworski

@molly_przew

5 years

Thanks to Zach Fuller ( @zl_fuller ), in collaboration with @heatshok , @LineKBay and many others, here is our first foray into precision medicine for corals:

Population genetics of the coral Acropora millepora: Towards a genomic predictor of bleaching

Although reef-building corals are rapidly declining worldwide, responses to bleaching vary both within and among species. Because these inter-individual differences are partly heritable, they should...

www.biorxiv.org

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Molly Przeworski

@molly_przew

5 years

@lkhayward and Guy Sella derive mathematical results for how phenotypic distribution and allele frequencies behave when the optimum value of a trait under stabilizing selection suddenly changes:

Polygenic adaptation after a sudden change in environment

Polygenic adaptation in response to selection on quantitative traits is thought to be ubiquitous in humans and other species, yet this mode of adaptation remains poorly understood. We investigate the...

www.biorxiv.org

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Molly Przeworski

@molly_przew

5 years

While these factors certainly matter, our results show they are not the only factors, and maybe not even the biggest factors, that influence the prediction accuracy of polygenic scores.

Variable prediction accuracy of polygenic scores within an ancestry group

Fields as diverse as human genetics and sociology are increasingly using polygenic scores based on genome-wide association studies (GWAS) for phenotypic prediction. However, recent work has shown...

www.biorxiv.org

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Molly Przeworski

@molly_przew

3 years

The newly anointed Dr. Felix Wu @FWuBiology , with the hat to prove it...

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Molly Przeworski

@molly_przew

7 years

Molly Schumer's work on where and why hybrid ancestry persists:

Natural selection interacts with the local recombination rate to shape the evolution of hybrid...

While hybridization between species is increasingly appreciated to be a common occurrence, little is known about the forces that govern the subsequent evolution of hybrid genomes. We considered this...

www.biorxiv.org

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Molly Przeworski

@molly_przew

3 years

Moreover, the model under which heritability is estimated is one in which genetic and environmental effects are assumed to be separable (in addition to which there may be a specific interaction term). 23/n

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Molly Przeworski

@molly_przew

3 years

Population genetics offers operational definitions of populations with which we model genetic variation: a set of individuals that draw their allele frequencies from the same set of distributions, say (e.g., ). 5/n

Inference of Population Structure Using Multilocus Genotype Data

AbstractWe describe a model-based clustering method for using multilocus genotype data to infer population structure and assign individuals to populations.

academic.oup.com

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Molly Przeworski

@molly_przew

4 years

A new thread about @arbelharpak and my paper on the evolution of group differences in changing environments, now out in @PLOSBiology : 1/n

The evolution of group differences in changing environments

This Essay discusses how complex traits may evolve under selection to maintain trait values in the face of changing environments; this scenario has implications for interpreting genetic differences...

journals.plos.org

Arbel Harpak

@arbelharpak

4 years

. @molly_przew & I wrote about how many complex traits may evolve under selection to maintain trait values in the face of changing environments. This scenario has implications for interpreting genetic signals of adaptation and combating racist arguments.

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Molly Przeworski

@molly_przew

3 years

Family designs such as sib GWAS can help tease apart direct genetic effects from all these other factors. (Precisely because family designs only include direct genetic effects, their prediction accuracy can be much lower than that of standard GWAS.) 18/n

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Molly Przeworski

@molly_przew

3 years

…Once we leave an experimental setting, we are effectively skating on thin ice, and whether the ice will hold depends on how far out we skate.” 13/n

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Molly Przeworski

@molly_przew

2 years

Many thanks for all the good wishes & kind messages.

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Molly Przeworski

@molly_przew

6 years

Congratulations to the newly minted Dr. Yuval Simons! @yuvalsim

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Molly Przeworski

@molly_przew

6 years

Anyone interested in a genome assembly of the staghorn coral Acropora millepora? Work by @zl_fuller , with lots of help from @MikhailMatz and @YiLiao9 . Scaffold N50 =1.23 Mb. Please RT.

Data

Draft genome of the staghorn coral Acropora millepora The draft assembly was constructed from a combination of PacBio and Illumina paired-end reads with 10X Genomics barcodes. Feel free to use the …

przeworskilab.com

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Molly Przeworski

@molly_przew

7 months

for our sampling choices to be sound, and because otherwise we run the risk of conveying the false impression that human biology somehow works differently in different socially defined ancestry categories. 8/n

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Molly Przeworski

@molly_przew

3 years

Whether that model is truly applicable to traits that arise mostly (entirely?) from interactions with the social environment, such as behavior, is not clear to me. 24/n

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Molly Przeworski

@molly_przew

7 years

Congratulations to my postdoc Priya Moorjani and to @Kelley__Harris for being awarded a 2017 BWF Career Award:

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Molly Przeworski

@molly_przew

5 years

Two papers by @GuyAmster & Guy Sella modeling effects of life history on the relative neutral diversity levels of X and autosomes: theory and data (across human pops, with David Murphy and @WillMilligan2 )

Changes in life history and population size can explain relative neutral diversity levels on X and...

In human populations, relative levels of neutral polymorphism on the X and autosomes differ markedly from each other and from the naive theoretical expectation of ¾. These differences have attracted...

www.biorxiv.org

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Molly Przeworski

@molly_przew

7 months

We have known for over half a century that most of the genetic diversity found in humans is found within any ancestry grouping, and have confirmed it many, many times over. 4/n

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Molly Przeworski

@molly_przew

7 years

Thoughtful review on selection pressures shaping lactase persistence in humans, by @lsegurel :

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Molly Przeworski

@molly_przew

3 years

Evolutionary and quantitative geneticists learn about heritability as informing the expected increase in a trait in response to selection in one generation. 20/n

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Molly Przeworski

@molly_przew

6 years

Thanks for featuring our results. Actually, our main finding--that the ratio of male to female mutations is already 3:1 by puberty and stays pretty stable with parental ages--is not subtle and is seen across data sets (Fig S2) 1/2

Gene Expression blog et al.

@gnxp_posts

6 years

The mutation accumulation controversy continues….

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Molly Przeworski

@molly_przew

3 years

Consider the claim that polygenic scores (PGS) can be useful (if noisy) predictors within a population but don’t “port” well to other populations. What is a population here? 4/n

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Molly Przeworski

@molly_przew

9 months

Congratulations to Dr. Carla Hoge!

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Molly Przeworski

@molly_przew

10 years

Our review on human germline mutation is officially out: http://t.co/hWmf2J04K8

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Molly Przeworski

@molly_przew

3 years

Quoting @magnusnordborg again: “With respect to confounding by population structure, the key qualitative difference is between controlling the environment experimentally, and not doing so… 12/n

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Molly Przeworski

@molly_przew

8 years

Priya Moorjani, Ziyue Gao and my review on "human germline mutation and the erratic molecular clock":

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Molly Przeworski

@molly_przew

4 years

Congratulations to @iagarwal2 , now Dr. Ipsita Agarwal!

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Molly Przeworski

@molly_przew

8 months

A reminder that abstracts for the annual meeting on Probabilistic Modeling in Genomics ( #ProbGen24 ) are due in a week (Feb 15). In Vienna this year, April 10-12 2024. Speakers and other information here:

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Molly Przeworski

@molly_przew

3 years

Truly interesting paper suggesting that the "end-of-lifespan somatic mutation burden" doesn't differ much across mammals with very different lifespans (at least in the tissue considered).

Alex Cagan

@ATJCagan

3 years

I am incredibly excited to share our preprint ‘Somatic mutation rates scale with lifespan across mammals’In this paper we provide an unprecedented description of somatic mutation across mammals. An illustrated tweetorial…[1/17]

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Molly Przeworski

@molly_przew

3 years

And it's worth considering if that is because of selection on the modifiers.

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Molly Przeworski

@molly_przew

3 years

Interesting and clever approach to characterizing participation bias, by Stefania Benonisdottir and Augie Kong:

The Genetics of Participation: Method and Analysis

Participation in a genetic study likely has a genetic component. Identifying such component is difficult as we cannot compare genetic information of participants with non-participants directly, the...

www.biorxiv.org

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Molly Przeworski

@molly_przew

7 years

Congratulations to Molly Schumer and 14 other recipients of the inaugural Hanna Gray HHMI fellowship:

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Molly Przeworski

@molly_przew

3 years

The fuzziness around the concept of population also has other implications, for example for how we interpret heritability, a concept that is defined within a population. 19/n

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Molly Przeworski

@molly_przew

7 years

Rapid evolution of the mutation spectrum in humans, by @Kelley__Harris and @jkpritch :

Rapid evolution of the human mutation spectrum

Heritable mutations tend to occur within different DNA sequence contexts in different human populations, suggesting that DNA replication and repair often change in efficacy over only a few hundred...

elifesciences.org

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Molly Przeworski

@molly_przew

7 years

When does PRDM9 binding lead to a rec. hotspot? Clever system and analysis by Nicolas Altemose, Simon Myers and co:

A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger...

In humans, specific sequence features can predict whether meiotic recombination occurs at sites bound by the protein PRDM9, whose DNA-binding zinc-finger domain can unexpectedly bind to gene promot...

elifesciences.org

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Molly Przeworski

@molly_przew

5 years

On that basis, we argue that the question of where polygenic scores apply is broader than ancestry, and inextricably linked to questions about the importance of GxE on direct and indirect effects.

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Molly Przeworski

@molly_przew

11 months

Helpful description of the choices of population designators in gnomad:

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Molly Przeworski

@molly_przew

8 years

Looking for a postdoc interested in germline mutation and its evolution: . Please RT.

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Molly Przeworski

@molly_przew

3 years

That those may result in lower mutation rates in some regions of the genome than others is interesting (*which* regions seem to differ among species).

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Molly Przeworski

@molly_przew

7 months

However, it is not the case that we need to diversify study participants because there is some big reservoir of genetic variants out there that we would miss if we did not sequence every socially defined ancestry grouping. 3/n

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Molly Przeworski

@molly_przew

7 years

Daniel Hooper on chromosomal inversion differences among passerine birds:

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Molly Przeworski

@molly_przew

7 years

What PRDM9 does and does not do in vertebrates -- work by @zachTWbaker & Molly Schumer & @shevayuki2778 :

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Molly Przeworski

@molly_przew

7 years

Simons & Sella's work relating stabilizing selection on a quantitative trait to allele frequencies & effect sizes:

A population genetic interpretation of GWAS findings for human...

GWAS in humans are revealing the genetic architecture of biomedical and anthropomorphic traits, i.e., the frequencies and effect sizes of variants that contribute to heritable variation in a...

arxiv.org

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Molly Przeworski

@molly_przew

7 months

The appropriate study design obviously depends on the question. For some questions, studying a wide range of ancestries will be important. For others, it will not. Understanding, and spelling out, when population designators matter to science and medicine is important: 7/n

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Molly Przeworski

@molly_przew

8 years

Guy Sella has asked me to post this link, re. the conversation around his 2016 PNAS paper:

Clarification

Our 2016 PNAS paper, “Life history effects on the molecular clock of autosomes and sex chromosomes”, has been the topic of an extensive discussion on Twitter over the past few days after Matthew Ha…

sellalab.biology.columbia.edu

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Molly Przeworski

@molly_przew

7 months

Registration is now open for the 2024 New York area Population Genetics meeting, organized by @bendesky . Keynote talks by @lindymcbr and @CedricFeschotte . At Columbia U, May 17, 2024. Register (free) and submit abstracts for talks or posters here:

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Molly Przeworski

@molly_przew

8 years

Our new results on the evol. of PRDM9 and recombination in vertebrates, @ZachTWBaker , Molly Schumer, @shevayuki2778 :

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