身為一個熱愛美食、喜歡在城市裡挖掘驚喜的人，臺中公益路一直是我最常出沒的地方之一。這條路可說是「臺中人的美食戰場」，從精緻西餐到創意火鍋，從日式丼飯到義式早午餐，每走幾步，就會有完全不同的特色料理餐廳。

這次我特別花了一整個月，實際造訪了公益路上十間口碑不錯的餐廳。有的是網友熱推的打卡名店，也有隱藏在巷弄裡的小驚喜。我以環境氛圍、口味表現、價格CP值與再訪意願為基準，整理出這篇實測評比。希望能幫正在猶豫去哪裡吃飯的你，找到那一間「吃完會想再來」的餐廳。

評比標準與整理方向

這次我走訪的10家餐廳橫跨不同料理類型，從高質感牛排館到巷弄系早午餐，每一間都有自己獨特的風格。為了讓整體比較更客觀，我依照以下四大面向進行評比，並搭配實際用餐體驗來打分。

整體而言，我希望這份評比不只是「哪家好吃」，而是幫你在不同情境下（約會、家庭聚餐、朋友小聚、商業午餐）都能快速找到合適的選擇。畢竟，美食不只是味覺的滿足，更是一段段與朋友共享的生活記憶。

10間臺中公益路餐廳評比懶人包

公益路向來是臺中人聚餐的首選地段，從火鍋、燒肉到中式料理與早午餐，每走幾步就有驚喜。以下是我實際造訪過的10間代表性餐廳清單，橫跨平價、創意、高級各路風格。

一頭牛日式燒肉｜炭香濃郁的和牛饗宴，約會聚餐首選

走在公益路上，很難不被 一頭牛日式燒肉 的木質外觀吸引。低調卻不失質感的門面，搭配昏黃燈光與暖色調的內裝，讓人一進門就感受到濃濃的日式職人氛圍。店內空間不大，但桌距規劃得宜，每桌皆設有獨立排煙設備，烤肉時完全不怕滿身油煙味。

餐點特色

一頭牛的靈魂，絕對是他們招牌的「三國和牛拼盤」。
嚴選的和牛部位，共八個部位、十樣餐點，讓人能從牛頭一路品嘗到牛尾。
油花分布均勻、切片厚薄恰好，經過炭火烤炙後香氣四溢，焦香與油脂在口中交融，入口即化的滑順感令人難忘。
值得一提的是，一頭牛的菜單設計十分彈性
想要一次體驗完整套餐也可以，偏好客製口味則能自由單點組合，不受套餐限制，想吃什麼就點什麼。
而且每桌都能選擇「自行燒烤」或「專人代烤」服務，代烤師的火侯掌握與節奏讓整體體驗更輕鬆愉快。
除了主角和牛，旬味野炊飯 與 主廚冰淇淋 也是隱藏版亮點，前者粒粒分明、香氣撲鼻；後者以香草與焙茶為基底，隨季節更換口味，完美收尾。整體服務親切熱情，特別是壽星還能享有 生日畫盤驚喜，讓慶祝時刻更添儀式感。

用餐體驗

整體節奏掌握得非常好。店員會在你剛想烤下一片肉時貼心遞上夾子、幫忙換烤網，讓人完全不用分心。整場用餐過程就像一場表演，從視覺、嗅覺到味覺都被滿足。
如果是第一次約會或慶祝特別節日，這裡的氛圍既不尷尬又不吵鬧，是營造氣氛的理想選擇。

綜合評分

地址：408臺中市南屯區公益路二段162號

電話：04-23206800

官網：http://www.marihuana.com.tw/yakiniku/index.html

小結語

一頭牛日式燒肉不僅是「吃肉的地方」，更像是一場五感盛宴。從進門那一刻到最後一道甜點，都能感受到他們對細節的用心。
若要在公益路找一間能讓人「邊吃邊微笑」的燒肉店，一頭牛 絕對值得列入你的必訪清單。

TANG Zhan 湯棧｜文青系火鍋代表，麻香湯底與視覺美感並重

在公益路這條美食戰線上，TANG Zhan 湯棧 是讓人一眼就會想走進去的那一種。
黑灰調的現代外觀、搭配微霧玻璃與招牌的「湯棧」燈字，呈現出一種低調的時尚感。
店內設計延續品牌主題，以「湯」為靈魂打造整體體驗，從裝潢到香氣，都有濃厚的溫潤氣息。

餐點特色

湯棧最有名的當然是它的「麻香鍋」。
湯底以雞骨與多種辛香料慢熬，香氣濃郁卻不嗆辣，入口後會在喉間留下柔和的花椒香。
「招牌麻油雞鍋」與「黃金牛奶鍋」也是人氣選項，特別是在冬天，溫潤的湯底配上滑嫩肉片，讓人每一口都覺得暖心。
他們的「滷肉飯」和「香蔥豆腐皮」更是許多老客人必點的靈魂配角，簡單卻有記憶點。

用餐體驗

整體氛圍比一般火鍋店更有質感。
桌距寬敞、燈光柔和，店員動作俐落又親切。即使客滿，也不會感覺吵雜或壓迫。
不論是一個人想靜靜吃鍋、或是朋友聚餐，湯棧都能給你剛剛好的距離與溫度。
值得一提的是，上菜速度快、湯底續湯毫不手軟，細節服務到位。

綜合評分

地址：408臺中市南屯區公益路二段248號

電話：04-22580617

官網：https://www.facebook.com/TangZhan.tw/

小結語

NINI 尼尼臺中店｜明亮寬敞的義式早午餐天堂

如果說前兩間是肉食愛好者的天堂，那 NINI 尼尼臺中店 絕對是想放鬆、聊聊天的好地方。餐廳外觀以白色系與大片玻璃窗為主，陽光灑進室內，讓人一踏入就有種度假般的輕盈感。假日早午餐時段特別熱鬧，建議提早訂位。

餐點特色

NINI 的菜單融合義式與臺灣人口味，選擇多樣且份量十足。主打的 松露燉飯 濃郁卻不膩口，米芯保留微Q口感；而 香蒜海鮮義大利麵 則以新鮮白蝦、花枝與淡菜搭配微辣蒜香，口感層次豐富。
此外，他們的薄餅披薩相當受歡迎，餅皮薄脆、餡料新鮮，是三五好友共享的好選擇。

用餐體驗

店內氣氛輕鬆不拘謹，無論是一個人帶電腦工作、或朋友聚餐，都能找到舒服角落。餐點上桌速度穩定，服務人員態度親切、補水與收盤都非常主動。整體節奏讓人覺得「時間變慢了」，很適合想遠離忙碌日常的人。

綜合評分

地址：40861臺中市南屯區公益路二段18號

電話：04-23288498

官網：https://nini.com.tw/

小結語

加分100%浜中特選昆布鍋物｜平價卻用心的湯頭系火鍋，家庭聚餐好選擇

在公益路這條高質感餐廳林立的戰場上，加分100%浜中特選昆布鍋物 走的是截然不同的路線。它沒有浮誇的裝潢、也沒有高價位的套餐，但靠著實在的湯頭與親切的服務，默默吸引許多回頭客。每到用餐時間，總能看到家庭或情侶三兩成群地圍著鍋邊聊天。

餐點特色

主打 北海道浜中昆布湯底，湯頭清澈卻不單薄，越煮越能喝出海藻與柴魚的自然香氣。
我這次點的是「牛奶昆布鍋」，入口時奶香與昆布香完美融合，搭配新鮮的牛五花肉片，滑順又不膩。
菜盤走健康取向，蔬菜比例高，連玉米、南瓜、豆皮都能吃出甜味；附餐的烏龍麵Q彈有嚼勁，吃完十分有飽足感。

用餐體驗

整體氛圍偏家庭取向，桌距寬敞、座位舒適，帶小孩來也不覺擁擠。店員態度親切，補湯、收盤都很勤快，給人一種「被照顧著」的安心感。
最難得的是，即使價位不高，食材新鮮度仍維持得很好，能感受到店家對品質的堅持。

綜合評分

地址：403臺中市西區公益路288號

電話：0910855180

官網：https://giafine100.com/

小結語

加分100%浜中特選昆布鍋物是一間「不浮誇、但會讓人想再訪」的火鍋店。它不追求豪華擺盤，而是用最簡單的湯頭與新鮮食材，傳遞出家常卻不平凡的溫度。
如果你想在公益路找一間可以放心帶家人一起吃的鍋物店，這裡絕對會讓人感到「加分」不少。

印月餐廳｜中式料理的藝術演繹，宴客與家庭聚會首選

說到臺中公益路的中式料理代表，印月餐廳 絕對是榜上有名。這間開業多年的餐廳以「中菜西吃」的概念聞名，把傳統中式料理以現代手法重新詮釋。從建築外觀到餐具擺設，每個細節都散發著低調的典雅氣息。
走進印月，挑高的空間、柔和的燈光與木質桌椅構成沉穩的氛圍。
不論是家庭聚餐、商務宴客，還是節日慶祝，都能找到恰到好處的格調。

餐點特色

印月最令人印象深刻的是他們將傳統中菜融入創意手法。
這次我品嚐的「松露雞湯」香氣濃郁、層次分明，一口下去既有中式的溫潤感，又帶出西式松露的奢華香氣。
「蒜香牛肋條」則是另一道招牌菜，外酥內嫩、油香十足，咬下去肉汁在口中散開，搭配特調醬汁非常過癮。
此外，他們的創意港點如「麻辣小籠包」與「金沙流沙包」也深受年輕客群喜愛，既保留經典又玩出新意。

用餐體驗

服務方面完全對得起餐廳的高級定位。從入座、點餐到上菜節奏，都拿捏得恰如其分。每道菜都會有服務人員細心介紹食材與吃法，讓人感受到「被款待」的尊榮感。
雖然價位偏中高，但在這樣的氛圍與品質下，物有所值。

綜合評分

地址：408臺中市南屯區公益路二段818號

電話：0422511155

官網：https://wein818.com/

小結語

印月餐廳是一間「不只吃飯，更像品味生活」的地方。
它成功地讓中式料理不再只是圓桌菜，而是能展現質感、講究細節的美食體驗。
若你在找一間能同時滿足味蕾與體面的餐廳，印月 絕對是公益路上的不敗經典。

KoDō 和牛燒肉｜極致職人精神，專為儀式感與頂級味覺而生

若要形容 KoDō 和牛燒肉 的用餐體驗，一句話足以總結——「像在欣賞一場關於肉的表演」。
隱身在公益路一隅，KoDō 的外觀低調典雅，店內以深色木質調與間接照明營造出沉穩氛圍。
從踏入店門那一刻開始，服務人員的態度、動線、聲音控制，全都精準到位，讓人彷彿走進日式劇場。

餐點特色

這裡主打 日本A5和牛冷藏肉，以「精切厚燒」的方式呈現。
我點的「壽喜燒風和牛套餐」是本日最驚艷的一道——服務人員現場以鐵鍋輕煎，再淋上特製壽喜燒醬汁，香氣瞬間瀰漫整桌。
肉片油花細緻、入口即化，搭配生蛋液後更添柔滑口感。
另一道「冷藏肋眼心」則保留了和牛的彈性與甜度，每一口都能感受到油脂與炭火交織出的層次。
即使是配角如「季節小菜」與「日式和風飯」也毫不馬虎，整體呈現出高級卻不造作的平衡。

用餐體驗

KoDō 的最大特色是「儀式感」。
每位店員的動作都有節奏，從擺盤、火候、換網到講解，都像排練過無數次的演出。
在這裡用餐，會自然地放慢速度，專注於每一口肉帶來的細膩變化。
特別推薦搭配店內的紅酒或日本威士忌，風味更加圓潤。

綜合評分

地址：403臺中市西區公益路260號

電話：0423220312

官網：https://www.facebook.com/kodo2018/

小結語

KoDō 和牛燒肉不是日常餐廳，而是一場體驗。
從環境、服務到食材，每個細節都讓人感受到對「完美」的執著。
若你想在公益路找一間能讓人留下深刻印象、適合紀念日慶祝的餐廳，KoDō 絕對是值得收藏的一次「味覺儀式」。

永心鳳茶｜在茶香裡用餐的優雅時光，臺味早午餐的新詮釋

走進 永心鳳茶公益店，彷彿進入一間有氣質的茶館。
柔和的燈光灑在復古綠牆上，搭配大理石桌面與金色餐具，整體氛圍既典雅又帶有一絲文青氣息。
這裡不只是喝茶的地方，更像是把「臺灣味」以早午餐的形式重新演繹。

餐點特色

永心鳳茶的餐點結合中式靈魂與西式擺盤，無論是「炸雞腿飯」還是「紅玉紅茶拿鐵」，都能讓人感受到熟悉卻不平凡的味道。
炸雞腿外酥內嫩，搭配自製酸菜與溏心蛋，鹹香中帶著層次感。
「鳳茶甜點拼盤」則以茶為靈魂——伯爵茶蛋糕、烏龍茶奶酪、紅茶雪酥，每一口都有細緻的香氣變化。
最特別的是他們的茶飲，從臺灣高山紅茶到金萱冷泡茶，每一壺都現泡現倒，香氣清雅。
對我而言，這不只是一頓飯，更是一段放鬆的午後儀式。

用餐體驗

店內服務人員態度溫和，對茶品介紹詳盡。上餐節奏剛好，不急不徐。
整體氛圍很「耐坐」，許多客人吃完正餐後仍會續點一壺茶聊天。
音樂輕柔、光線柔和，是那種可以靜靜待上兩小時的地方。

綜合評分

地址：40360臺中市西區公益路68號三樓(勤美誠品)

電話：0423221118

官網：https://linktr.ee/yonshin

小結語

永心鳳茶讓人重新定義「臺味」。
它不走傳統路線，而是把熟悉的元素以更細緻、更現代的方式呈現。
無論是姊妹下午茶、親子餐聚，或是想一個人沉澱片刻，永心鳳茶 都是一處能讓人慢下來、品味生活的好地方。

三希樓｜老饕級江浙功夫菜，穩重又帶人情味的中式饗宴

位於公益路上的 三希樓 是許多臺中老饕的口袋名單。
它沒有浮誇的裝潢，卻有一種低調的自信。從大門進入，就能聞到淡淡的醬香與蒸氣味，那是正宗江浙菜的靈魂。
整體裝潢以深木色為主，搭配圓桌與包廂設計，非常適合家庭聚餐或請客宴會。

餐點特色

三希樓的菜色以 江浙與港式料理 為主，兼顧傳統與現代風味。
我這次點了「東坡肉」與「蝦仁炒飯」，兩道都展現了主廚深厚的火候功力。
東坡肉油亮卻不膩，入口即化、鹹甜交織；蝦仁炒飯粒粒分明、香氣十足，每一口都吃得到鑊氣。
此外，「小籠包」皮薄多汁，是幾乎每桌必點的招牌；港點類如「金牌流沙包」與「干貝燒賣」也都表現穩定。

用餐體驗

三希樓的服務給人一種老派但貼心的感覺。
店員上菜節奏掌握得很好，會主動幫忙分菜、收盤，態度沉穩而不打擾。
最讓我印象深刻的是，這裡的客群非常多元——有帶長輩的家庭、公司聚餐，也有情侶共度節日，卻都能在同一空間裡感到自在。

綜合評分

地址：408臺中市南屯區公益路二段95號

電話：0423202322

官網：https://www.sanxilou.com.tw/

小結語

三希樓是一間「吃得出功夫」的餐廳。
它不追求創新，而是用穩定的味道與真材實料，抓住每一位饕客的胃。
如果你想在公益路上找一間能兼顧長輩口味、氣氛又不拘謹的中餐廳，三希樓 絕對是最穩妥的選擇。

一笈壽司｜低調奢華的無菜單日料，職人手藝詮釋旬味極致

在熱鬧的公益路上，一笈壽司 低調得幾乎不顯眼。
外觀簡約，沒有華麗招牌，只有小小的木質門面與柔黃燈光。
一推開門，迎面而來的是日式杉木香氣與寧靜的氛圍，吧檯座位整齊排列，主廚站在中間，彷彿舞臺上的演出者。

餐點特色

一笈壽司採 Omakase（無菜單料理） 形式，每一餐都由主廚根據當日食材設計。
我這次選擇中價位套餐（約 $1200），共十多道料理，從前菜、小鉢、刺身、握壽司到甜點一氣呵成。
「比目魚鰭邊握」是整場最驚豔的瞬間——主廚以火槍輕炙，油脂瞬間釋放，入口後化成柔滑香氣。
「甜蝦海膽軍艦」則完美展現鮮度與層次感，海膽甘甜、甜蝦緊實。
搭配主廚親自調配的醬汁，每一口都像在品嚐季節的節奏。

用餐體驗

整場用餐約90分鐘，節奏緩慢但沉穩。
主廚會邊料理邊與客人互動，介紹魚種產地與食材處理方式。
雖然整體空間不大，但氣氛極佳——柔和的音樂、清酒的香氣、刀刃切魚時的聲音，讓人完全沉浸其中。
特別喜歡他們最後的甜點「焙茶奶酪」，收尾清爽優雅，為整場體驗畫下完美句點。

綜合評分

地址：408臺中市南屯區公益路二段25號

電話：0423206368

官網：https://www.facebook.com/YIJI.sushi/

小結語

一笈壽司是一間真正讓人「放慢呼吸」的餐廳。
這裡沒有多餘擺盤，也不靠噱頭，而是以主廚對食材的尊重與技術堆疊出一場味覺饗宴。
若你想在公益路體驗日本料理最純粹的精神，一笈壽司 絕對值得你預約、靜靜期待。

茶六燒肉堂｜人氣爆棚的和牛燒肉聖地，肉香與幸福感同時滿分

若要票選公益路上「最難訂位」的餐廳，茶六燒肉堂 絕對名列前茅。
不管平日或假日，用餐時段幾乎一位難求。外觀以木質格柵搭配大面玻璃設計，呈現出年輕又有質感的風格。店內空間明亮、桌距適中，播放著輕快的音樂，整體氛圍熱鬧中帶點高級感，是許多年輕人聚餐、慶生的首選地。

餐點特色

茶六主打 和牛燒肉套餐，價格約落在 $700–$1000 間，份量與品質兼具。
我這次點的是「厚切牛舌套餐」，肉片厚實彈牙，略帶脆感，搭配鹽蔥提味剛剛好。
另一道「和牛拼盤」也相當受歡迎，油花分布均勻、香氣濃郁，輕烤幾秒即可入口即化。
套餐附餐部分也相當用心：沙拉新鮮、味噌湯濃郁，最後還有一份「茶香冰淇淋」作結尾，香氣清爽，完美收尾。

用餐體驗

茶六的服務效率相當高。店員親切、換網勤快、補水速度快，整場用餐流程流暢無壓力。
雖然客人很多，但環境維持得乾淨整潔，動線規劃良好。
最令人印象深刻的是他們的 整體節奏拿捏得剛剛好 ——餐點上桌快、氣氛熱絡，卻不會讓人覺得匆忙。
不論是朋友聚會、家庭聚餐，甚至是情侶約會，都能找到各自的樂趣。

綜合評分

地址：403臺中市西區公益路268號

電話：0423281167

官網：https://inline.app/booking/-L93VSXuz8o86ahWDRg0:inline-live-karuizawa/-LUYUEIOYwa7GCUpAFWA

小結語

茶六燒肉堂用「穩定品質＋輕奢氛圍」抓住了臺中年輕族群的心。
不論是第一次約會還是老朋友重聚，都能在這裡找到屬於燒肉的快樂節奏。
若你在公益路只想挑一家「保證不踩雷」的燒肉店，茶六燒肉堂 絕對是首選。

吃完10家公益路餐廳後的心得與結語

吃完這十家餐廳後，臺中公益路不只是一條美食街，而是一段生活風景線。

有的餐廳講究細膩與儀式感，像 一頭牛日式燒肉 與 一笈壽司，讓人感受到食材最純粹的美好

有的則以親切與溫度打動人心，像 加分昆布鍋物、永心鳳茶，讓人明白吃飯不只是為了飽足，而是一種被照顧的幸福。

而像茶六燒肉堂、TANG Zhan 湯棧 這類人氣名店，則用穩定的品質與熱絡的氛圍，成為許多臺中人心中「想吃肉就去那裡」的代名詞。

這十家店，構成了公益路最動人的縮影

有華麗的，也有溫柔的；有傳統的，也有創新的。

 每一家都在自己的風格裡發光，讓人吃到的不只是料理，而是一種生活的溫度與節奏。

對我而言，這不僅是一場美食旅程，更是一趟關於「臺中味道」的回憶之旅。

FAQ：關於臺中公益路美食常見問題

Q1：公益路哪一區的餐廳最集中？
 最熱鬧的區段大約在「公益路與黎明路口」一帶，這裡聚集了許多知名餐廳，從高級燒肉到早午餐通通有。
像 一頭牛日式燒肉、TANG Zhan 湯棧、茶六燒肉堂 都在這附近，交通方便、停車也相對容易。

Q2：需要提前訂位嗎？
 公益路的熱門餐廳幾乎都建議 提早3～5天訂位，尤其是假日或節慶期間。
特別是 一頭牛日式燒肉、KoDō 和牛燒肉、一笈壽司 這幾家，若臨時前往幾乎很難有位。

最後的話

若要用一句話形容這趟美食之旅，我會說：
「在公益路，吃飯不是選擇，而是一種享受。」
這條路上的每一次用餐，都像一段城市裡的小旅行。
下次當你不確定想吃什麼時，不妨沿著公益路走一圈，或許下一家，正好就是你新的最愛。

一笈壽司整體值得推薦嗎？

如果你也和我一樣喜歡用味蕾探索一座城市，那就把這篇公益路美食攻略收藏起來吧。茶六燒肉堂肉質如何？

無論是約會、慶生、家庭聚餐，或只是想犒賞一下辛苦的自己——這條路上永遠會有一間剛剛好的餐廳在等你。KoDō 和牛燒肉家庭聚餐合適嗎？

下一餐，不妨從這10家開始。三希樓單點比較好嗎？

打開手機、約上朋友，讓公益路成為你生活裡最容易抵達的小確幸。加分100%浜中特選昆布鍋物慶生氣氛夠嗎？

如果你有私心愛店，也歡迎留言分享，一頭牛日式燒肉春酒活動適合在這裡辦嗎？

你的推薦，可能讓我下一趟美食旅程變得更精彩。永心鳳茶網路評價符合期待嗎？

Regions of the protein’s flexibility: not very flexible (blue), moderately flexible (green/yellow) and highly flexible (red). However, both the central alpha helix and the N-terminus (start of the protein) display stable folding in comparison with the rest of the protein. Credit: Adam Damry International team of researchers investigates how evolution forms the structure and function of a newly emerged protein in flies. Proteins are the key component in all modern forms of life. Haemoglobin, for example, transports the oxygen in our blood; photosynthesis proteins in the leaves of plants convert sunlight into energy; and fungal enzymes help us brew beer and bake bread. Researchers have long been examining the question of how proteins mutate or come into existence in the course of millennia. That completely new proteins – and, with them, new properties – can emerge practically out of nothing, was inconceivable for decades, in line with what the Greek philosopher Parmenides said: “Nothing can emerge from nothing” (ex nihilo nihil fit). Working with colleagues from the USA and Australia, researchers from the University of Münster have now reconstructed how evolution forms the structure and function of a newly emerged protein in flies. This protein is essential for male fertility. The results have been published in the journal Nature Communications. Background It had been assumed up to now that new proteins emerge from already existing proteins – by a duplication of the underlying genes and by a series of small mutations in one or both gene copies. In the past ten years, however, a new understanding of protein evolution has come about: proteins can also develop from so-called non-coding DNA (deoxyribonucleic acid) – in other words, from that part of the genetic material which does not normally produce proteins – and can subsequently develop into functional cell components. This is surprising for several reasons: for many years, it had been assumed that, in order to be functional, proteins had to take on a highly developed geometrical form (a “3D structure”). It had further been assumed that such a form could not develop from a gene emerging at random, but would require a complex combination of amino-acids enabling this protein to exist in its functional form. Fruit flies (shown here mating) served as the study model. Credit: Mareike Kopping Despite decades of trying, researchers worldwide have not yet succeeded in constructing proteins with the desired 3D structures and functions, which means that the “code” for the formation of a functioning protein is essentially unknown. While this task remains a puzzle for scientists, nature has proven to be more adept at the formation of new proteins. A team of researchers headed by Prof. Erich Bornberg-Bauer, from the Institute of Evolution and Biodiversity at the University of Münster, discovered, by comparing the newly analyzed genomes in numerous organisms, that species not only differ through duplicated protein-coding genes adapted in the course of evolution. In addition, proteins are constantly being formed de novo (“anew”) – i.e. without any related precursor protein going through a selection process. The vast majority of these de novo proteins are useless, or even slightly deleterious, as they can interfere with existing proteins in the cell. Such new proteins are quickly lost again after several generations, as organisms carrying the new gene encoding the protein have impaired survival or reproduction. However, a select few de novo proteins prove to have beneficial functions. These proteins integrate into the molecular components of cells and eventually, after millions of years of minor modifications, become indispensable. There are some important questions which many researchers wonder about in this context: How do such novel proteins look like upon birth?  How do they change, and which functions do they assume as the “new kids on the block?” Spearheaded by Prof. Bornberg-Bauer’s group in Münster, an international team of researchers has answered this question in much detail for “Goddard,” a fruit fly protein that is essential for male fertility. Methodology The research proceeded on three related fronts across three continents. At the College of the Holy Cross in Massachusetts, USA, Dr. Prajal Patel and Prof. Geoff Findlay used CRISPR/Cas9 genome editing to show that male flies that do not produce Goddard are sterile, but otherwise healthy. Meanwhile, Dr. Andreas Lange and PhD student Brennen Heames of Prof. Bornberg-Bauer’s group used biochemical techniques to predict the shape of the novel protein in present-day flies. They then used evolutionary methods to reconstruct the likely structure of Goddard ~50 million years ago when the protein first arose. What they found was quite a surprise: “The ancestral Goddard protein looked already very much like the ones which exist in fly species today,” Erich Bornberg-Bauer explains. “Right from the beginning, Goddard contained some structural elements, so-called alpha-helices, which are believed to be essential for most proteins.” To confirm these findings, the scene shifted to the Australian National University in Canberra, where Dr. Adam Damry and Prof. Colin Jackson used intensive, computational simulations to verify the predicted shape of the Goddard protein. They validated the structural analysis of Dr. Lange and showed that Goddard, in spite of its young age, is already quite stable – though not quite as stable as most fly proteins that are believed to have existed for longer, perhaps hundreds of millions of years. The results match up with several other current studies, which have shown that the genomic elements from which protein-coding genes emerge are activated frequently – tens of thousands of times in each individual. These fragments are then “sorted” through the process of evolutionary selection. The ones which are useless or harmful – the vast majority – are quickly discarded. But those which are neutral, or are slightly beneficial, can be optimized over millions of years and changed into something useful. Reference: “Structural and functional characterization of a putative de novo gene in Drosophila” by Andreas Lange, Prajal H. Patel, Brennen Heames, Adam M. Damry, Thorsten Saenger, Colin J. Jackson, Geoffrey D. Findlay and Erich Bornberg-Bauer, 12 March 2021, Nature Communications. DOI: 10.1038/s41467-021-21667-6 Funding: The research undertaken received funding from the European Grant EsCat within the Horizon 2020 Research and Innovation Framework Programme No. 722610 (Münster), from the ARC Centres of Excellence in Peptide and Protein Science and Synthetic Biology (Australia), and from an NSF CAREER Grant #1652013 (USA).

Researchers developed a gene sequencing technique using a new machine learning algorithm to accurately identify the origin and concentration of tagged DNA. This method effectively separates bacterial DNA from human and other non-bacterial DNA. Previous studies of a genetic on/off switch may have been confounded by contamination, but Mount Sinai scientists have created a new tool for accurately determining whether it plays a role in human disease. A tiny team of cutting-edge medical experts has been examining a biochemical, DNA tagging mechanism that turns genes on and off for decades. Some have recently discovered evidence of it in plants, flies, human brain tumors, and even bacteria, which has long been researched in bacteria. A new study by scientists at the Icahn School of Medicine at Mount Sinai, however, suggests that there may be a problem: a large portion of the evidence for its presence in higher organisms may be caused by bacterial contamination, which was challenging to detect using current experimental techniques. New Sequencing Technique to Differentiate DNA Sources To solve this problem, the researchers developed a special gene sequencing technique that makes use of a brand-new machine learning algorithm to precisely determine the origin and concentration of tagged DNA. This made it easier for them to separate bacterial DNA from human and other non-bacterial cell DNA. The findings reported in Science confirmed the hypothesis that this mechanism may exist naturally in cells other than bacteria, although the levels were significantly lower than those reported in some earlier research and were easily influenced by bacterial contamination or modern experimental techniques. Similar results were obtained in experiments using human brain cancer cells. “Pushing the boundaries of medical research can be challenging. Sometimes the ideas are so novel that we have to rethink the experimental methods we use to test them out,” said Gang Fang, PhD, Associate Professor of Genetics and Genomic Sciences at Icahn Mount Sinai. “In this study, we developed a new method for effectively measuring this DNA mark in a wide variety of species and cell types. We hope this will help scientists uncover the many roles these processes may play in evolution and human disease.” Researchers at the Icahn School of Medicine at Mount Sinai developed an advanced method for determining whether cells may use an obscure DNA tagging system for turning genes on or off. Credit: Courtesy of Do lab, Mount Sinai, N.Y., N.Y. Exploring DNA Adenine Methylation in Various Organisms The study focused on DNA adenine methylation, a biochemical reaction which attaches a chemical, called a methyl group, to an adenine, one of the four building-block molecules used to construct lengthy DNA strands and encode genes. This can “epigenetically” activate or silence genes without actually altering DNA sequences. For instance, it is known that adenine methylation plays a critical role in how some bacteria defend themselves against viruses. For decades, scientists thought that adenine methylation strictly happened in bacteria whereas human and other non-bacterial cells relied on the methylation of a different building block—cytosine—to regulate genes. Then, starting around 2015, this view changed. Scientists spotted high levels of adenine methylation in plant, fly, mouse, and human cells, suggesting a wider role for the reaction throughout evolution. However, the scientists who performed these initial experiments faced difficult trade-offs. Some used techniques that can precisely measure adenine methylation levels from any cell type but do not have the capacity to identify which cell each piece of DNA came from, while others relied on methods that can spot methylation in different cell types but may overestimate reaction levels. In this study, Dr. Fang’s team developed a method called 6mASCOPE which overcomes these trade-offs. In it, DNA is extracted from a sample of tissue or cells and chopped up into short strands by proteins called enzymes. The strands are placed into microscopic wells and treated with enzymes that make new copies of each strand. An advanced sequencing machine then measures in real time the rate at which each nucleotide building block is added to a new strand. Methylated adenines slightly delay this process. The results are then fed into a machine learning algorithm which the researchers trained to estimate methylation levels from the sequencing data. Refining the Understanding of DNA Methylation “The DNA sequences allowed us to identify which cells—human or bacterial—methylation occurred in while the machine learning model quantified the levels of methylation in each species separately,” said Dr. Fang, Initial experiments on simple, single-cell organisms, such as green algae, suggested that the 6mASCOPE method was effective in that it could detect differences between two organisms that both had high levels of adenine methylation. The method also appeared to be effective at quantifying adenine methylation in complex organisms. For example, previous studies had suggested that high levels of methylation may play a role in the early growth of the fruit fly Drosophila melanogaster and of the flowering weed Arabidopsis thaliana. In this study, the researchers found that these high levels of methylation were mostly the result of contaminating bacterial DNA. In reality, the fly and the plant DNA from these experiments only had trace amounts of methylation. Likewise, experiments on human cells suggested that methylation occurs at very low levels in both healthy and disease conditions. Immune cell DNA obtained from patient blood samples had only trace amounts of methylation. Similar results were also seen with DNA isolated from glioblastoma brain tumor samples. This result was different than a previous study, which reported much higher levels of adenine methylation in tumor cells. However, as the authors note, more research may be needed to determine how much of this discrepancy may be due to differences in tumor subtypes as well as other potential sources of methylation. Finally, the researchers found that plasmid DNA, a tool that scientists use regularly to manipulate genes, may be contaminated with high levels of methylation that originated from bacteria, suggesting this DNA could be a source of contamination in future experiments. “Our results show that the manner in which adenine methylation is measured can have profound effects on the result of an experiment. We do not mean to exclude the possibility that some human tissues or disease subtypes may have highly abundant DNA adenine methylation, but we do hope 6mASCOPE will help scientists fully investigate this issue by excluding the bias from bacterial contamination,” said Dr. Gang. “To help with this we have made the 6mASCOPE analysis software and a detailed operating manual widely available to other researchers.” Reference: “Critical assessment of DNA adenine methylation in eukaryotes using quantitative deconvolution” by Yimeng Kong, Lei Cao, Gintaras Deikus, Yu Fan, Edward A. Mead, Weiyi Lai, Yizhou Zhang, Raymund Yong, Robert Sebra, Hailin Wang, Xue-Song Zhang and Gang Fang, 3 February 2022, Science. DOI: 10.1126/science.abe7489 This work was supported by the National Institutes of Health (GM139655, HG011095, AG071291); the Icahn Institute for Genomics and Multiscale Biology; the Irma T. Hirschl/Monique Weill-Caulier Trust; the Nash Family Foundation; and the Department of Scientific Computing at the Icahn School of Medicine at Mount Sinai. Methods validation using Mass Spectrometry was supported by the collaborators at the Chinese Academy of Sciences (XDPB2004) and the National Natural Science Foundation of China (22021003).

A killer whale in the Salish Sea is observed harassing a porpoise, a behavior that has long perplexed scientists. A study from Wild Orca and UC Davis’ SeaDoc Society investigates what may be behind it. Credit: Wild Orca Scientists investigate a perplexing behavior. For many years, scientists have been puzzled by the behavior of Pacific Northwest fish-eating killer whales, who have been seen harassing and sometimes killing porpoises without eating them. A study recently published in Marine Mammal Science, co-led by Deborah Giles of Wild Orca and Sarah Teman of the SeaDoc Society, a program of the UC Davis School of Veterinary Medicine, looked at more than 60 years of recorded interactions between Southern Resident killer whales and porpoises in the Salish Sea to better understand why they exhibit this behavior. Southern Resident killer whales are an endangered population, numbering only 75 individuals. Their survival is intimately tied to the fortunes of Chinook salmon — also an endangered species. Without enough Chinook salmon, these whales are in danger of extinction. “I am frequently asked, why don’t the Southern Residents just eat seals or porpoises instead?” said Giles. “It’s because fish-eating killer whales have a completely different ecology and culture from orcas that eat marine mammals — even though the two populations live in the same waters. So we must conclude that their interactions with porpoises serve a different purpose, but this purpose has only been speculation until now.” Three plausible explanations While scientists have recorded instances of Southern Resident killer whales engaging in porpoise harassment as early as 1962, reasons for this behavior have long remained a mystery. Giles, Teman, and a team of collaborators analyzed 78 documented incidents of porpoise harassment from 1962 to 2020. The study suggests three plausible explanations: Social play: Porpoise harassment may be a form of social play for killer whales. Like many intelligent species, these whales sometimes engage in playful activities to bond, communicate, or simply enjoy themselves. This behavior might benefit group coordination and teamwork. Hunting practice: Another hypothesis suggests that porpoise harassment might hone their salmon-hunting skills. Southern Resident killer whales could view porpoises as moving targets to practice their hunting techniques, even if they do not intend to consume them. Mismothering behavior: This theory suggests that the whales may be attempting to provide care for porpoises they perceive as weaker or ill–a manifestation of their natural inclination to assist others in their group. Females have been witnessed carrying their deceased calves and have been seen similarly carrying porpoises. “Mismothering behavior — also known as ‘displaced epimeletic behavior’ to scientists— might be due to their limited opportunities to care for young,” Giles explained. “Our research has shown that due to malnutrition, nearly 70% of Southern Resident killer whale pregnancies have resulted in miscarriages or calves that died right away after birth.” Salmon specialists Despite these intriguing insights, Giles, Teman, and their collaborators acknowledge that the exact reason behind porpoise harassment may never be fully understood. What is clear, however, is that porpoises are not a part of the Southern Resident killer whale diet. Southern Resident killer whale diets are highly specialized for salmon, making the idea of eating porpoises highly unlikely. “Killer whales are incredibly complex and intelligent animals. We found that porpoise-harassing behavior has been passed on through generations and across social groupings. It’s an amazing example of killer whale culture,” Teman says. “Still, we don’t expect the Southern Resident killer whales to start eating porpoises. The culture of eating salmon is deeply ingrained in Southern Resident society. These whales need healthy salmon populations to survive.” This research underscores the importance of conserving salmon populations in the Salish Sea and throughout the whales’ entire range. Maintaining an adequate supply of salmon is vital for the survival and well-being of Southern Resident killer whales and the overall health of the Salish Sea ecosystem. Affinity for play This study comes at a time when a separate population of killer whales on the Iberian Peninsula has drawn international headlines for interacting with, and on three occasions, sinking boats off the coast of Portugal and Spain. Ultimately, the Southern Resident killer whales and the Iberian Peninsula orcas are two different populations with distinct cultures. One thing the two might have in common is their affinity for play behavior. Reference: “Harassment and killing of porpoises (“phocoenacide”) by fish-eating Southern Resident killer whales (Orcinus orca)” by Deborah A. Giles, Sarah J. Teman, Samuel Ellis, John K. B. Ford, Monika W. Shields, M. Bradley Hanson, Candice K. Emmons, Paul E. Cottrell, Robin W. Baird, Richard W. Osborne, Michael Weiss, David K. Ellifrit, Jennifer K. Olson, Jared R. Towers, Graeme Ellis, Dena Matkin, Courtney E. Smith, Stephen A. Raverty, Stephanie A. Norman and Joseph K. Gaydos, 28 September 2023, Marine Mammal Science. DOI: 10.1111/mms.13073 The study was funded by Wild Orca and SeaDoc Society. Additional partners include the University of Exeter, Fisheries and Oceans Canada, Orca Behavior Institute, National Oceanic and Atmospheric Administration, Cascadia Research, The Whale Museum, Center for Whale Research, Ocean Research College Academy (ORCA) at Everett Community College, Bay Cetology, North Gulf Oceanic Society, George Mason University, and Marine-Med.

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