November 25, 2004

Human History and the Y Factor

The Y-chromosome is vital in the study of human evolution, writes Laoise Moore , winner of this year's 'Irish Times'/RIA biochemistry writing competition

Our DNA connects us with the past. We inherit DNA, our genetic material, from our parents, who inherited it from their parents, and they from their parents and so on back to the origins of life. Our DNA is organised into 23 pairs of chromosomes, half from each parent. DNA occurs as a code of four letters: A, T, G and C. Variations in this code occur among individuals and are what make us distinct at a genetic level. This variation also provides a powerful tool for understanding the origins and history of the human species.

In particular, the Y-chromosome has become a critical tool in the study of human evolution. The Y-chromosome is a sex-determining chromosome - its presence confers maleness - and it is passed from father to son.

Unlike other chromosomes, it escapes the shuffling effects of recombination, whereby genetic material is exchanged between maternal and paternal chromosomes. Instead, a father simply copies his Y-chromosome and passes it unchanged to his son. Thus it is inherited in a simpler way than other chromosomes.

This copying process is usually accurate, but occasionally mistakes are made - for example, a T might be changed to C. When this Y-chromosome is passed to future generations, the mistake is copied with it. In this way the combination of mutations that have accumulated on a Y-chromosome over a period of time bear a record of its past.

Advances in molecular biology have allowed the identification of many mutations that distinguish Y-chromosomes from each other and it is possible to build a detailed profile of these mutations. A profile of mutations on a Y-chromosome is called a haplotype. Through the comparison of a worldwide sample of haplotypes we can trace the history of human Y-chromosome evolution and, by extension, the paternal history of the human species.

It is possible to compare the Y-haplotypes of a group of men to see how closely related they are. If they are closely related, their haplotypes will be very similar. Conversely, if the haplotypes are very different from one another we can infer that they are not closely related.

We can use patterns of mutations that have occurred in a worldwide sample of human Y-chromosomes to reconstruct a tree relating all the Y chromosome lineages of the world to each another. This is known as the Y-chromosome phylogeny. Looking at the branching order (or topology) of the phylogeny, together with the frequencies and geographic distributions of the various haplotypes, we can begin to unravel the origins and dispersals of modern humans throughout the world.

It is also possible to estimate a time frame for these mutational events, since mutations are thought to accumulate at a fairly constant rate. It is possible to estimate how long since two Y- chromosomes had a common ancestor from the number of differences between them. Similarly, it is possible to estimate the time to most recent common ancestor (TMRCA) of a group of Y-chromosomes. By analysing the mutational diversity in a worldwide sample of Y- chromosomes, it is possible to estimate the TMRCA of all the Y- chromosomes in humans alive today.

The TMRCA of the tree of extant human Y-chromosomes is surprisingly recent, with estimates ranging from about 50,000 to 150,000 years ago. We are a very young species. The deepest branches on the tree are not found in populations outside sub-Saharan Africa. This suggests that the most recent common ancestor of all extant Y- chromosomes lived in Africa between 50,000 and 150,000 years ago.

It is likely that there were many more humans alive at this time. That he is our most recent common ancestor simply implies that all other Y-lineages have since become extinct.

The deepest mutation on the Y chromosome tree in non-African populations is called M168. It is found in many African and all non- African Y-chromosomes. This indicates that the M168 mutation must be very old, since it must have arisen in the common ancestor of some African and all non-African populations. Molecular genetic estimates suggest it is around 40,000 years old. This indicates that all non- African Y-chromosomes are descended from an ancestor who lived in an African population, which expanded out of Africa within the last 40,000 years.

Since then, other mutations have accumulated on some M168- bearing Y-chromosomes, which have allowed us to trace the migration paths taken by populations expanding out of Africa.

For example, M89 is a mutation that occurred on an M168-bearing Y- chromosome. M89 chromosomes are found in east African populations, and also in most Asian, European and Native American populations. The age and geographic distribution of chromosomes carrying M89 suggests that it arose in a north-east African population that was involved in a major expansion event out of Africa and into Eurasia between 45,000 and 30,000 years ago.

The fact that M89 is so common in non-African populations suggests that the initial group that left Africa was composed of a very small group of individuals, and from this group all the major non-African populations (except perhaps Australians) derive.

Later mutations occurring on M89 chromosomes allow us to trace further migration events. M9 is one such mutation, which is found in many Eurasian and Amerindian Y-chromosomes. This suggests that the population in which M9 arose expanded widely.

Further mutational analysis indicates that M9 chromosomes later divided into two main groups, one carrying the M45 mutation that spread to north Asia, and one carrying M3, which spread from Siberia to the American Indian populations. This suggests the ancestors of American Indians came from Asia, through Siberia and across the Bering Strait.

In the M45-bearing population in Asia, a mutation called M173 arose. This expanded westwards around 30,000 years ago and reached Europe, the Middle East, Central Asia and Northern India/Pakistan. It is thought that bearers of this mutation were the first modern humans to enter Europe and they spread widely throughout Europe during the Upper Palaeolithic or Late Stone Age. Many extant European Y-chromosomes belong to this lineage.

The above examples illustrate how analysis of Y-chromosome variation can trace the origins of human populations, but Y- chromosomes can also be used to illuminate more regional questions of human history.

For example, we can ask: Who are the ancestors of European men? Modern human populations entered Europe during the Upper Paleolithic period 30,000 to 40,000 years ago, bearing the M173 mutation. The archaeological record indicates that Neanderthal populations lived in Europe at this time, but the recent African origin of all extant human Y-chromosomes indicates that the Neanderthals were completely replaced by the incoming modern human populations.

There were other human migrations into Europe - some in the Upper Palaeolithic and some in later periods, such as the spread of Neolithic farmers from the Near East from about 10,000 years ago - and the participants in these migrations brought other Y-chromosome lineages into Europe.

The M269 mutation arose on some European M173 Y-chromosomes and today these chromosomes are found at high frequency along the Atlantic coast of Europe.

Since these are descended from the M173 chromosomes of the original Upper Palaeolithic inhabitants, it is thought that the populations of the Atlantic coast of Europe are largely the descendants of the original colonising populations. The populations farther east have been influenced by the genetic impact of later migrating populations.

Analysis of Irish Y-chromosomes carried out at the department of genetics in Trinity College Dublin has shown that M269 exists at strikingly high frequency in the Irish population, with about 85 per cent of all Irish Y-chromosomes belonging to this lineage.

This is one of the highest frequencies in Europe, and suggests thatthe Irish Y-chromosome population is in large part descended from the original European Palaeolithic colonisers.

The genetic legacies of more recent demographic events may also be investigated using Y-chromosome molecular genetics. For example, a study of Y-chromosome variation in Britain has detected the genetic impact of Anglo-Saxons and Vikings, who brought distinctive Y-chromosomes when they invaded.

In a vast region of Asia, from the Pacific Ocean to the Caspian Sea, Y-chromosome variation has revealed the trace of a Y- chromosome lineage thought to be descended from Genghis Khan (c.1162- 1227), who established the largest land empire in history. This lineage appears to have arisen in Mongolia around 1,000 years ago and to have spread throughout Asia in a short time.

The geographic distribution of this lineage matches the boundaries of the regions ruled by the Khans. Around eight per cent of the males sampled in the Asian study possessed this Y- chromosome. This implies that around 16 million men, or 0.5 per cent of the world's total, possess the Y-chromosome of Genghis Khan.

The Y-chromosome currently provides the best-resolved phylogeny in the human genome, allowing an increasingly fine-scale resolution of worldwide Y-chromosome variation. It illuminates the origins, migrations, expansions, colonisations and evolution of our ancestors.

As molecular genetic techniques for the discovery and analysis of mutations improve, analysis of Y-chromosome variation will allow us to continue to uncover the sometimes-surprising genetic legacy of human history.

Laoise Moore is studying for a PhD at the Department of Genetics, Trinity College Dublin