Big Dog, Little Dog: Mutation Explains Range of Canine Sizes大狗，小狗——基因突变解释体型大小

埃文·卡拉韦　徐江/译

The genetic variant probably comes from ancient wolves.

基因變体可能来自古代狼。

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.

从吉娃娃到大丹犬，狗的体型大小差异比世界上其他任何哺乳动物都大。这种差异背后的突变已经追溯到了一个出人意料的源头——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.

突变位于一个名叫IGF1的基因附近，15年前研究人员就认定该基因在家犬体型大小差异方面起着重要作用。这也是目前确认的大约20多个此类基因中最早被发现的。人们努力想找出到底是哪一个基因变体导致突变，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.

埃莱娜·奥斯特兰德说：“IGF1基因一直困扰着我们。”奥斯特兰德是马里兰州贝塞斯达市国家人类基因组研究所的遗传学家。她领衔了2007年的研究，率先确定了IGF1基因在狗的体型方面的作用，后又于《当代生物学》杂志上发表研究成果，圆满完成了这一探索。

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.

古代狗是过去3万年间由狼驯化而来，体型有一定程度的差异。但是，随着过去200年人类培育出现代犬种，目前不同犬种的体型呈现出巨大差异——最大品种是最小品种体型的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.

奥斯特兰德和同事们，包括法国国家健康与医学研究院、雷恩大学遗传学家若瑟兰·普拉赛，分析了1400多种犬科动物的基因组，包括古代狗、狼、郊狼及230个现代犬种。

Growth control

成长控制

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.

他们比较了狗和野外犬科动物IGF1基因附近区域的变异与体型大小，有一个变体十分显眼。该变体所在的那段DNA编码一个名叫长链非编码RNA的分子，这种分子参与控制有效生长激素——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.

研究人员找出了该变体的两种形态，或者说两个等位基因。所有品种中，携带两份其中一种等位基因的狗往往体重不足15公斤，而携带两份另一种等位基因的情况，在体重超过25公斤的狗身上更为常见。奥斯特兰德说，两种等位基因各有一份的狗往往体型中等。与有两个小体型等位基因的狗相比，有两个大体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.

研究人员查看了其他犬科动物基因组，发现存在类似的关联。奥斯特兰德说：“不仅仅狗是这样。狼、狐狸、郊狼等无一例外。所有犬科动物都是如此。”

Diminutive11 ancestors

小体型祖先

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.

研究人员认为，从进化的角度来讲，与小体型相关的等位基因要比大体型等位基因古老得多。他们分析过的郊狼、豺狼、狐狸及多数其他犬科动物都有两个 “小”版等位基因，说明这个基因版本存在于这些动物的某个共同祖先身上。

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.

大体型等位基因是何时进化的，这一点尚不清楚。研究人员发现，一种5.3万年前生活在西伯利亚的古代狼携带了一份这种等位基因。其他古代狼和现代的灰狼则往往携带两份，说明大体型等位基因可能对狼有利。

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.”

加州大学洛杉矶分校进化生物学家罗伯特·韦恩说，以前科学家中的主流观点认为，小体型很可能与比较新近的基因变化有关，且这些变化可能为家犬所独有。“这完全改变了先前的说法。这正是整个研究了不起的地方。”

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.

来自马萨诸塞大学伍斯特分校陈氏医学院的遗传学家埃莉诺·卡尔松说，这一研究可能是一个迹象，意味着狗是由与现代灰狼不一样的小体型狼驯化而来。她说：“我们不清楚演化成狗的狼究竟长什么样。”

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.

研究人员也提醒说，关于狗的体型的研究还远远不够完整。普拉赛想弄清楚变体如何影响IGF1蛋白水平。变体也不是决定狗的体型的唯一因素：品种之间的差异约有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.”

卡爾松说：“我们讨论的不是使狼变成吉娃娃那么小的一种突变。我们讨论的是许多突变中的一个，它倾向于使你变得更小一点。”