Big Dog, Little Dog: Mutation Explains Range of Canine Sizes大狗，小狗——基因突變解釋體型大小

埃文·卡拉韋　徐江/譯

The genetic variant probably comes from ancient wolves.

基因變體可能來自古代狼。

From chihuahuas1 to great Danes， dogs differ more in size than any other mammal species on the planet. A mutation behind such variation has been traced to an unexpected source： ancient wolves.

從吉娃娃到大丹犬，狗的體型大小差異比世界上其他任何哺乳動物都大。這種差異背后的突變已經追溯到了一個出人意料的源頭——古代狼。

The mutation lies near a gene called IGF12， which researchers flagged 15 years ago as having a major role in the size variation of domestic dogs. It was the first of around two dozen such genes identified. But efforts to pinpoint3 the gene variant responsible had come up empty4.

突變位于一個名叫IGF1的基因附近，15年前研究人員就認定該基因在家犬體型大小差異方面起著重要作用。這也是目前確認的大約20多個此類基因中最早被發(fā)現的。人們努力想找出到底是哪一個基因變體導致突變，但未能如愿。

“IGF1 has been a thorn in our side5，” says Elaine Ostrander， a geneticist at the US National Human Genome Research Institute in Bethesda， Maryland， who led the 2007 study that first identified IGF1s role in dog size， as well as the study in Current Biology6 that now fulfils the quest.

埃萊娜·奧斯特蘭德說：“IGF1基因一直困擾著我們?！眾W斯特蘭德是馬里蘭州貝塞斯達市國家人類基因組研究所的遺傳學家。她領銜了2007年的研究，率先確定了IGF1基因在狗的體型方面的作用，后又于《當代生物學》雜志上發(fā)表研究成果，圓滿完成了這一探索。

Ancient dogs， domesticated from wolves in the past 30，000 years， differed in size to some extent. But the current extreme size differences—the largest breeds are up to 40 times bigger than the smallest—emerged in the past 200 years， as humans established modern breeds.

古代狗是過去3萬年間由狼馴化而來，體型有一定程度的差異。但是，隨著過去200年人類培育出現代犬種，目前不同犬種的體型呈現出巨大差異——最大品種是最小品種體型的40倍。

Ostrander and colleagues including geneticist Jocelyn Plassais at INSERM-University of Rennes， France， analysed the genomes7 of more than 1，400 canids8， including ancient dogs， wolves， coyotes and 230 modern dog breeds.

奧斯特蘭德和同事們，包括法國國家健康與醫(yī)學研究院、雷恩大學遺傳學家若瑟蘭·普拉賽，分析了1400多種犬科動物的基因組，包括古代狗、狼、郊狼及230個現代犬種。

Growth control

成長控制

When they compared variation in the region around the IGF1 gene with body size in dogs and wild canids， one variant stood out. It lies in a stretch of DNA that encodes a molecule called a long non-coding RNA9， which is involved in controlling levels of the IGF1 protein， a potent growth hormone.

他們比較了狗和野外犬科動物IGF1基因附近區(qū)域的變異與體型大小，有一個變體十分顯眼。該變體所在的那段DNA編碼一個名叫長鏈非編碼RNA的分子，這種分子參與控制有效生長激素——IGF1蛋白的水平。

The researchers identified two versions， or alleles10， of the variant. Across all breeds， dogs with two copies of one allele tended to weigh less than 15 kilograms， whereas two copies of the other version were more common in dogs weighing more than 25 kilograms. Dogs with one copy of each allele tended to be intermediate in size， says Ostrander. Canines with two copies of the large-bodied allele also had higher levels of the IGF1 protein in their blood， compared with those with two copies of the ‘small allele.

研究人員找出了該變體的兩種形態(tài)，或者說兩個等位基因。所有品種中，攜帶兩份其中一種等位基因的狗往往體重不足15公斤，而攜帶兩份另一種等位基因的情況，在體重超過25公斤的狗身上更為常見。奧斯特蘭德說，兩種等位基因各有一份的狗往往體型中等。與有兩個小體型等位基因的狗相比，有兩個大體型等位基因的狗血液中IGF1蛋白水平更高。

When the researchers looked at the genomes of other canids， they found a similar relationship. “This wasnt just a dog story. This was a wolf story and a fox story and a coyote story and everything story. It was canine-wide，” says Ostrander.

研究人員查看了其他犬科動物基因組，發(fā)現存在類似的關聯。奧斯特蘭德說：“不僅僅狗是這樣。狼、狐貍、郊狼等無一例外。所有犬科動物都是如此?！?/p>

Diminutive11 ancestors

小體型祖先

The researchers think that the allele linked to small bodies is， evolutionarily， much older than the large-bodied version. Coyotes， jackals， foxes and most other canids they analysed had two copies of the ‘small version， suggesting that this version was present in a common ancestor of these animals.

研究人員認為，從進化的角度來講，與小體型相關的等位基因要比大體型等位基因古老得多。他們分析過的郊狼、豺狼、狐貍及多數其他犬科動物都有兩個 “小”版等位基因，說明這個基因版本存在于這些動物的某個共同祖先身上。

Its not clear when the large-bodied allele evolved. The researchers found that an ancient wolf that lived in Siberia around 53，000 years ago carried one copy of this version. Other ancient wolves and modern grey wolves tend to have two， suggesting that the large-bodied allele might have been beneficial to wolves.

大體型等位基因是何時進化的，這一點尚不清楚。研究人員發(fā)現，一種5.3萬年前生活在西伯利亞的古代狼攜帶了一份這種等位基因。其他古代狼和現代的灰狼則往往攜帶兩份，說明大體型等位基因可能對狼有利。

The prevailing12 view among scientists used to be that small body size was probably linked to relatively new genetic changes， potentially unique to domestic dogs， says Robert Wayne， an evolutionary biologist at the University of California， Los Angeles. “This turns the whole story on its head13. Thats whats marvellous about the whole thing.”

加州大學洛杉磯分校進化生物學家羅伯特·韋恩說，以前科學家中的主流觀點認為，小體型很可能與比較新近的基因變化有關，且這些變化可能為家犬所獨有?！斑@完全改變了先前的說法。這正是整個研究了不起的地方。”

The study could be a sign that dogs were domesticated from smaller-bodied wolves， dissimilar to present-day grey wolf populations， says Elinor Karlsson， a geneticist at the University of Massachusetts Chan Medical School in Worcester. “We dont know what the wolves that led to dogs even looked like，” she says.

來自馬薩諸塞大學伍斯特分校陳氏醫(yī)學院的遺傳學家埃莉諾·卡爾松說，這一研究可能是一個跡象，意味著狗是由與現代灰狼不一樣的小體型狼馴化而來。她說：“我們不清楚演化成狗的狼究竟長什么樣?！?/p>

Researchers also caution that the story of dog size is far from complete. Plassais wants to work out how the variants influence levels of the IGF1 protein. And the variant isnt the only determinant14 of size in dogs： the IGF1 gene itself accounts for about 15% of variation between breeds.

研究人員也提醒說，關于狗的體型的研究還遠遠不夠完整。普拉賽想弄清楚變體如何影響IGF1蛋白水平。變體也不是決定狗的體型的唯一因素：品種之間的差異約有15%是由IGF1基因本身造成的。

“Were not talking about a mutation that makes a wolf chihuahua-sized，” says Karlsson. “Were talking about one of many mutations that tends to make you a bit smaller.”

卡爾松說：“我們討論的不是使狼變成吉娃娃那么小的一種突變。我們討論的是許多突變中的一個，它傾向于使你變得更小一點?！?/p>