{"id":360775,"date":"2025-08-21T00:51:11","date_gmt":"2025-08-21T00:51:11","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/360775\/"},"modified":"2025-08-21T00:51:11","modified_gmt":"2025-08-21T00:51:11","slug":"what-makes-some-identical-twins-look-and-behave-differently","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/360775\/","title":{"rendered":"What makes some identical twins look and behave differently?"},"content":{"rendered":"

Metastable epialleles may sound like complex science, but they help explain why identical animals can still look and act differently. For years, scientists asked why two mice with identical DNA<\/a> could differ, with one obese and yellow, the other lean and brown. This strange difference stems from epigenetics \u2014 changes in gene activity that don\u2019t come from changes in the DNA sequence.<\/p>\n

Over twenty years ago, scientists noticed something unusual while studying a mouse strain called agouti viable yellow, or Avy. Some of these genetically identical mice became yellow and obese, while others stayed brown and lean. The genes weren\u2019t different, but gene expression was \u2014 driven by DNA methylation, small tags added to DNA during development.<\/p>\n

In 2003, researchers found that giving pregnant mice nutrients like folate and B12<\/a> could affect methylation in their offspring. This increased methylation led more of the pups to develop brown coats and healthier weights. <\/p>\n

The study showed a strong link between maternal diet and epigenetic change passed to the next generation. The Avy gene controls the changes in color and weight and is known as a metastable epiallele. Its methylation is set randomly during early development and then remains the same across all tissues for life.<\/p>\n

Study helps explain why identical animals can still look and act differently. (CREDIT: Shutterstock) <\/p>\n

Since then, researchers have asked how many metastable epialleles \u2014 or MEs \u2014 exist in mice. Could they help explain other unexpected differences in lab animals with identical genes? A recent study finally answers this question using the full mouse genome. <\/p>\n

Dr. Robert A. Waterland at Baylor College of Medicine<\/a> led the research, published in Nucleic Acids Research<\/a>. His team searched the mouse genome for these rare and unpredictable epigenetic sites. Their results shocked many researchers: metastable epialleles are extremely rare.<\/p>\n

A Comprehensive Scan of the Mouse Genome<\/p>\n

To study MEs, the team used deep whole-genome bisulfite sequencing to map DNA methylation in detail. They examined three tissues \u2014 brain, kidney, and liver \u2014 in ten mice from the same inbred C57BL\/6J strain. These mice were genetically identical, so any differences in methylation had to come from epigenetic<\/a> factors.<\/p>\n

Related Stories<\/p>\n

The scientists searched for methylation<\/a> patterns that were consistent in each mouse but varied between different mice. This pattern defines metastable epialleles \u2014 consistent across tissues but different between individuals. After scanning millions of sites, the researchers found only 29 that matched their criteria.<\/p>\n

Dr. Chathura J. Gunasekara, a co-first author and bioinformatics expert, explained the study\u2019s approach and surprising result. \u201cWe performed a comprehensive, unbiased scan of epigenetic variation across the entire mouse genome\u2026 only 29 metastable epialleles,\u201d he said.<\/p>\n

Rethinking the Role of Maternal Diet<\/p>\n

For years, scientists believed maternal nutrition could change methylation at MEs, as seen in the 2003 Avy study. Waterland\u2019s new study suggests this isn\u2019t true for most metastable epialleles. The team tested nutrients like folate and B12 that support methylation in developing embryos<\/a>. They saw no changes in methylation at the 29 MEs they identified.<\/p>\n

Graphical abstract. (CREDIT: Robert Waterland, et al.) <\/p>\n

\u201cAnother surprising finding was that maternal diet\u2026 had no effect,\u201d said co-author Uditha Maduranga, a bioinformatics analyst on the project. This challenges the idea that methyl donor supplements always influence methylation at epigenetic<\/a> sites. The finding matters because it shows the Avy gene may be unusual, not typical of other metastable epialleles. Most MEs seem to set methylation randomly during development and remain mostly unaffected by the mother\u2019s diet.<\/p>\n

The Role of Transposons and Sex<\/p>\n

Most of the 29 metastable epialleles were linked to IAPs \u2014 or intracisternal A-particle elements \u2014 a kind of transposon. These \u201cjumping genes\u201d can move to new locations in the genome and change gene regulation. The MEs tended to occur at the beginning of IAP elements, suggesting a region of increased sensitivity.<\/p>\n

The team also found methylation differences linked to the sex of the mouse, even before sex organs developed. These early methylation patterns may explain later differences in disease risk between males and females. Some methylation differences were shaped by transcription factors like CTCF and KRAB zinc finger proteins. These molecules help control when and how genes are turned on or off during development. They may play key roles in forming and preserving methylation patterns at sensitive genome<\/a> sites.<\/p>\n

Screen for SIV identifies a small number of MEs, but also sex-associated SIV regions. (CREDIT: Robert Waterland, et al.) How This Compares to Humans<\/p>\n

While the team found just 29 MEs in mice, earlier studies revealed over 10,000 similar regions in humans. These human regions are called CoRSIVs \u2014 correlated regions of systemic interindividual variation. Most CoRSIVs link to genetic variation<\/a> and don\u2019t qualify as true metastable epialleles.<\/p>\n

Still, they show strong sensitivity to early embryo environments and have been linked to human diseases. \u201cIronically,\u201d said Waterland, \u201cestablishment of DNA methylation at human CoRSIVs is very sensitive\u2026 just like at the Avy metastable epiallele.\u201d \u201cIn addition, CoRSIVs are strongly implicated in human disease,\u201d he added.<\/p>\n

The contrast between mice and humans raises questions about how good mouse models really are for human epigenetics. Waterland believes that using outbred mice \u2014 which have more genetic variety \u2014 would better reflect human variation. This study adds an important piece to understanding how early development influences lifelong gene expression<\/a> and health. <\/p>\n

Waterland\u2019s findings suggest scientists should reconsider which animal models work best for studying human epigenetics. \u201cRather than the inbred mice used in biomedical research for decades,\u201d he said, \u201coutbred mice are likely a better model.\u201d<\/p>\n

What the Future Holds<\/p>\n

This study answers one long-standing question but opens several new ones. Why are MEs so rare in inbred mice but so common in human data? How do transcription factors and development conditions combine to lock in methylation patterns for life? <\/p>\n

Can scientists someday use this knowledge to predict or prevent diseases linked to early epigenetic changes<\/a>? These are critical questions for future research. For now, Waterland\u2019s study offers clearer insight into how epigenetic variation forms \u2014 and how we might study it next.<\/p>\n","protected":false},"excerpt":{"rendered":"Metastable epialleles may sound like complex science, but they help explain why identical animals can still look and…\n","protected":false},"author":2,"featured_media":360776,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[267,70,16,15],"class_list":{"0":"post-360775","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-science","10":"tag-uk","11":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/115064018346718865","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/360775","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=360775"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/360775\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/360776"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=360775"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=360775"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=360775"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}