The beautiful cover of the August issue of GENETICS was created by artist Michele Banks to commemorate the fiftieth anniversary of a pivotal moment in the history of evolutionary biology: the 1966 publication of a pair of GENETICS papers using protein electrophoresis to reveal that natural genetic diversity is bountiful. Thanks to a conversation between two specialists from different fields, these papers delivered a jolt of data to a stagnating debate. As part of the GENETICS Centennial celebrations, Brian Charlesworth, Deborah Charlesworth, Jerry Coyne, and Charles Langley discuss this work and its impact in “Hubby and Lewontin on Protein Variation in Natural Populations: When Molecular Genetics Came to the Rescue of Population Genetics“
In 1966, two contrasting views of genetic variability held sway. The “classical” view posited that mutations were rare and harmful, and that most individuals in a population are homozygous for the wild type version of a gene. The “balance” view held that balancing selection often maintained multiple common versions of a gene in a population, with many individuals being heterozygous. But the debate was stuck. “Population genetics seemed doomed to a perpetual struggle between alternative interpretations of great masses of inevitably ambiguous data,” wrote Lewontin in 1991.
Part of the trouble was a lack of hard data. In the age before DNA sequencing, describing genetic variation in the wild was a piecemeal task, only possible in a few select cases. Geneticists could study the variability of specific traits with a clear genetic basis, such as snail shell patterns or human blood groups, or they could study major chromosomal variants, such as inversion polymorphisms in wild fruit flies. They could infer the extent of variation through statistical analysis of breeding experiments. But without the ability to isolate specific genes, there was no way to perform an unbiased survey of genome-wide variation.
As a student of pioneering evolutionary geneticist Theodosius Dobzhansky, Richard Lewontin was keenly aware of this problem, but could not find the right method to solve it. Then, a few years after graduating, he visited the University of Chicago and met a biochemist, John Hubby, who was analyzing proteins from fruit flies using electrophoresis. Hubby would grind up individual flies, run the protein extract on gels, and detect specific proteins through their enzymatic activity. Each protein migrated through an electric current applied to the gel at a characteristic speed. But if the same protein differed slightly between individuals —whether in charge, size, or shape—its migration pattern might be altered. Lewontin realized the biochemists already had the missing technique that population geneticists sorely needed:
“…not enough credit is given to the effect of talking to other people and dealing with other people. There’s too much emphasis on the great creative act of a great mind and it’s not like that. […] Here I was with a problem looking for a solution and here a guy was with a solution looking for a problem, and we got together. Many of the things we did in our lab in Chicago arose in the course of a conversation.”
So convinced was Lewontin of the importance of this insight that he moved his lab to the University of Chicago, where he collaborated with Hubby. The pair quickly began surveying protein variability in Drosophila pseudoobscura, a wild cousin of the famous laboratory fruit fly beloved by geneticists. As Lewontin had hoped, they found electrophoretic variation in D. pseudoobscura proteins showed simple Mendelian inheritance, meaning the protein differences they were measuring corresponded directly to genetic variants. But to their surprise, around a third of the surveyed genes varied between individuals. To quantify this variation across five different D. pseudoobscura populations, they developed a simple summary of genetic diversity, “H” or expected heterozygosity, that is still widely used today. H provides an estimate of the chance that any two alleles at one gene are different, and with this measure, Hubby and Lewontin demonstrated substantial natural variability in all the sampled populations.
But was the richness of protein variation just a fruit fly quirk? The beauty of the new approach was it could be applied immediately to any organism, not just those, like Drosophila, with long histories in the lab:
“Here was a technique that could be learned easily by any moderately competent person, that was relatively cheap as compared with most physiological and biochemical methods, that gave instant gratification by revealing before one’s eyes the heritable variation in unambiguously scoreable characters, and most important, could be applied to any organism whether or not the organism could be genetically manipulated, artificially crossed, or even cultivated in the laboratory or greenhouse.”
Charlesworth et al. write of the method’s immediate impact: “It triggered an explosion of “find ’em and grind ’em” studies of variability in natural populations of numerous different species, from bacteria to humans, which showed that the levels of variability originally found in Drosophila and humans were not unusual.”
It also turned out to be a boon for understanding the evolutionary histories of organisms without fossil records. In a parallel eruption of protein electrophoresis studies, geneticists combined the protein data with measures of “genetic distance” between species (such as Nei’s “D”) to estimate phylogenies and divergence times between populations and species.
Ironically, Lewontin was wrong in predicting the methods would break the deadlock of the classical/balance debate. Instead, the influx of data raised new questions and complications, and stimulated new avenues for debate. Hubby and Lewontin’s method is the direct ancestor of today’s studies of genetic variation using genome sequence data, but the field’s fundamental question remains active: What are the most important causes of genetic variation?
The solution to the problem of natural diversity may well emerge from another meeting between scientists from different fields, drawn into a new conversation.
CITATIONS
Charlesworth, B., Charlesworth, D., Coyne, J. A., & Langley, C. H. (2016). Hubby and Lewontin on Protein Variation in Natural Populations: When Molecular Genetics Came to the Rescue of Population Genetics. Genetics,203(4), 1497-1503. DOI: 10.1534/genetics.115.185975
http://www.genetics.org/content/203/4/1497
Hubby, J. L., & Lewontin, R. C. (1966). A molecular approach to the study of genic heterozygosity in natural populations. I. The number of alleles at different loci in Drosophila pseudoobscura. Genetics, 54(2), 577.
http://www.genetics.org/content/54/2/577
Lewontin, R. C., & Hubby, J. L. (1966). A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura.Genetics, 54(2), 595.
http://www.genetics.org/content/54/2/595
Lewontin, R. C. (1991). Twenty-five years ago in Genetics: electrophoresis in the development of evolutionary genetics: milestone or millstone?. Genetics,128(4), 657.
http://www.genetics.org/content/128/4/657
Cristy Gelling is a science writer, lapsed yeast geneticist, and former Communications Director at the GSA.
View all posts by Cristy Gelling »Read more in
-
Where are they now? Rosalind Franklin Young Investigator Award recipients share updates on their research
Rosalind Franklin Young Investigator Award applications are open–make sure you submit your application or nomination of a colleague by September 30, 2024.
-
University of Minnesota researchers map genome of the last living wild horse species
The study, published in G3: Genes|Genomes|Genetics, is part of larger conservation efforts to save Przewalski’s horse.
-
Congratulations to the Spring 2024 DeLill Nasser Awardees!
GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Spring 2024! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…
-
Carolyn Damilola: an NFS Rising Scientist on a lifelong quest to learn more
Carolyn Damilola is an NFS Rising Scientist from Nigeria doing respiratory system research and paving the way for scientists from underrepresented communities through mentorship.
-
What does a good microgrant proposal look like?
Members of the Microgrant Review Committee share their tips for a successful proposal.
-
The first piece of the facial recognition puzzle
New research in GENETICS gives a first peek at the molecular pathway involved in recognizing faces.
-
New Senior Editor Amy MacQueen joins GENETICS
A new senior editor is joining GENETICS in the Genome Integrity and Transmission section. We’re excited to welcome Amy MacQueen to the editorial team.
-
Block party on the zebrafish sex chromosome
Research in G3 identifies a gene regulatory block of the zebrafish genome responsible for overseeing the maternal-to-zygotic-transition.
-
Unraveling the mysteries of duckweed: epigenetic insights from Spirodela polyrhiza
Research published in G3 offers insight into the impact of DNA methylation on clonal propagation in asexually reproducing plants.
-
A microbiologist’s quest to understand CRISPR in bacterial self-defense
2024 Genetics Society of America Medal recipient Luciano Marraffini determined how CRISPR-Cas systems destroy genetic targets with precision, paving the way for gene editing technology development.
-
Unlocking mysteries of trait and disease heritability in dogs
2024 Edward Novitski Prize recipient Elaine Ostrander, a pioneer of the domestic dog model, discovered numerous genes affecting dog size, morphology, behavior, and disease susceptibility—many of which have relevance in humans.
-
GSA and collaborators Personal Genetics Education & Dialogue and Reclaiming STEM Institute launch NSF-funded BIO-LEAPS project to support culture change in genetics
We are thrilled to announce that the Genetics Society of America (GSA) is collaborating with the Personal Genetics Education & Dialogue (PGED) based in the Department of Genetics at Harvard Medical School, and the Reclaiming STEM Institute (RSI) on a Leading Culture Change Through Professional Societies of Biology (BIO-LEAPS) grant from the U.S. National Science…
-
Daman Saluja: Navigating Science and Policy in India
In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the GSA Early Career Scientist…
-
A fly geneticist’s journey into discovering rules of organ development
2024 George W. Beadle Award recipient Deborah Andrew discovered new genes and pathways in Drosophila salivary gland organogenesis. Now, her work can help optimize cell secretion in therapeutic applications and fight malaria.
-
Małgorzata Gazda: How receiving the DeLill Nasser Award helped her land her dream job
Have you ever experienced an event that changes the course of your life, or in this case, your career? Małgorzata (Gosia) Gazda is Assistant Professor at the University of Montreal and in 2022, she received the DeLill Nasser Award for Professional Development in Genetics, which she used to attend and present at the 2022 Population,…
-
Hongyu Zhao joins GENETICS as new Senior Editor
A new senior editor is joining GENETICS in the Statistical Genetics and Genomics section. We’re excited to welcome Hongyu Zhao to the editorial team.
-
GSA Member Julio Molina Pineda Receives DeLill Nasser Award, Shines at TAGC 2024
“At any career stage, the GSA membership is an amazing investment for any genetics professional!” Julio Molina Pineda is a PhD Candidate in Cell and Molecular Biology and a Research Assistant at the University of Arkansas, and a Doctoral Academy Fellow at the Lewis Lab. In 2023, Julio was awarded the DeLill Nasser Award for…
-
In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation
Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…
-
Congratulations to the #Fungal24 Poster Award winners!
We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…
-
Poster presentation tips for TAGC 2024
You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…
-
Maximize your TAGC 2024 experience
A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…
-
Early Career Leadership Spotlight: Sarah Petrosky
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…
-
TAGC 2024 Early Career Award Winners
GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024. Don’t miss the opportunity…
-
Preeminent geneticists recognized with revamped GSA Awards
In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…
-
Fly Board funds outreach programs to spread the word about Drosophila research
In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…
-
New members of the GSA Board of Directors: 2024–2026
We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…
-
The Fly Meeting is one-of-a-kind! Dros 2025 organizers share their excitement
The 66th Annual Drosophila Research Conference promises to be a meeting rich with the latest in Drosophila research as well as opportunities to advance your career and connect with a global community of 1,400+ scientists. The organizers Todd Nystul, Michelle Bland, Leila Rieder, Amanda Crocker, and Justin Crocker are hard at work, planning a conference…
-
Early Career Leadership Spotlight: Olufemi Osonowo
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Olufemi Adekunle OsonowoCareer Development SubcommitteeDalhousie University Research Interest Metabolomics and genomics are two distinct but complimentary approaches that offer valuable insights into the underlying mechanisms of complex traits, such…
-
Early Career Leadership Spotlight: Hector Mendoza
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Hector MendozaCommunication and Outreach SubcommitteeUniversity of Michigan Research Interest My research goals converge around the evolution of sexual reproduction. During my doctoral program, I investigated mitochondrial inheritance, a mechanism…