My Dinner Party Guests 2 – Dr Katherine Pollard

Here’s something you may not ever have thought of. When you line up a gene sequence in the genome of a hen, a chimp and a human and find that they are exactly the same, you can assume that this element of our biology is quite essential and pretty much set in stone.

That’s because our common ancestor is apparently a crocodile that lived hundreds of millions of years ago. If we were going to diverge from the pattern set at that time we have all had plenty of chances to do so, because mutations occur constantly. It’s estimated that every human is born with about 100 personal mutations. Few stick. Between chimpanzees and humans our 1% difference has accumulated in 6 million years.

Logically then, if you want to know what sets human beings apart from all the rest, you need to identify what bits of DNA are most different in humans – even from chimps – our closest relatives.

In Scientific American [May 2009] there was an article entitled What Makes Us Human? – a report by Dr Katherine S Pollard into the work she’d done to analyse that 1% difference. It was reprinted in their December 2012 issue as one of their best articles on human evolution. Here’s a copy of the raw article I downloaded from the internet.

Dr Katherine Pollard

Dr Katie Pollard was in the right place at the right time. The human genome was sequenced in 2001 as she did her PhD. She then worked on the team that sequenced the chimp genome – published in 2005. It was natural – and, presumably, encouraged by funding patterns – that she would want to use the techniques and insights she’d gained to build knowledge about the human genome.

In her human evolution work, Dr Pollard wanted to find out which changes were most pivotal in separating us from other primates. So she and her team sifted through the 1% of different DNA – 30 million ‘letters’ – to find the 2700 sequences that had changed fastest in humans. Then they had to work out what these bits actually did.

Her team found three pivotal mutations in our DNA – one set that improved control of the facial muscles, making speech easier, another set – bringing about the opposition of finger and thumb – which presumably increased dexterity and tool use.

But the most rapidly evolving human mutation had helped to develop the characteristic folds in the human cerebral cortex. Presumably, before we could have all the thoughts, we had to have a place to put them. . .

This sequence is called HAR1 – part of a newly recognised part of DNA that tell other sequences what to do – they don’t do anything themselves – sort of genetic middle management. [HAR simply stands for Highly Active Region.] Dr Pollard says: “..the secret is to have rapid change occur in sites where these changes make an important difference in an organism’s functioning”.

When you ask successful people about their career trajectory they often look bemused and say that “one thing led to another”. Pollard’s search for the human difference reveals exactly that kind of process. It’s not just a truism but the actual evolutionary mechanism. Be in the right place at the right time and beneficial mutations are more likely to stick. Encourage one thing to lead to another and maybe it will. Streamline the process of change and change will be more likely to happen.

In a talk she gave for the Leakey Foundation, Pollard gave two examples of this in our digestive systems. Lactose intolerance is the natural state for adult mammals – but it is a kind of on/off switch. The human populations where it is off – where adults tolerate milk – tend to be descended from herders – where the ability to drink milk would have given a survival advantage.

The other example relates to the digestion of starches – turning them into the sugars our body needs. Almost all humans have more than one copy of the amylase enzyme that does this – but if chimps have it at all, it is confined to their pancreas. Humans have two to four copies of the enzyme and, interestingly, the inhabitants of regions where grains and other starchy foods exist are more likely to have multiple copies. That means amylase will live in multiple sites in their bodies, including the saliva. It’s basically been copied and pasted there from the pancreas region – again, conveying an evolutionary advantage.

In her lab at UCSF’s Gladstone Institutes Dr Pollard also has an evolutionary advantage. She has worked on the genetics of human evolution and of our microbial companions – the human biome. – and has developed models, techniques and algorithms that allow us to make sense of the bewildering complexity of genome and biome. She has just been appointed to the Chan Zuckerberg Biohubas one of 47 Investigators – with a brief to pursue her biggest riskiest ideas. Scientific heaven.

She has become a prime example of her own core truth that one thing leads to another – and to its corollary – that timing is everything!