It is a complex story but basically his argument from the genetics is that while we focus on the culture of ancient Rome (and Greece, and others), this was largely a product of cultural forces arising in urban centers and not from genetics. At their peak these urban centers are usually wonderful concoctions of people from many genetic lineages across imperial domains. However, the urban centers are not representative of their nations and the genetic story usually reverts to the mean of the region, no matter how cosmopolitan it might appear..
When the urban centers collapse, the genetic heterogeneity disappears and is ultimately and eventually replaced by the genetic patterns from the countryside. Which makes sense given that all urban centers are demographic sinks. They do not produce enough natural reproduction (children) to sustain the city population. Cities always grow from immigration from the countryside or from elsewhere. Growth is almost always substantially fueled by inbound migrants from the countryside. As they peak, they attract peoples from far and wide. But those heterodox genetic lineages are all washed away with an urban collapse and the people from the countryside repopulate the shrunken city.
Rome conquered vast swaths of Europe and the Mediterranean world 2,000 years ago. The imperial city exerted a magnetic pull upon the conquered peoples. It was hungry for their labor and their skills. Artisans from every shore of what the Romans called “Our Sea'' streamed into the capital city to build and beautify it. Augustus declared that he had “found Rome a city of bricks and left it a city of marble.” All roads did lead to Rome. But this was not the first time Italy was an irresistible destination. Thousands of years earlier, prehistoric Neolithic farmers from Anatolia and nomadic pastoralists from Central Europe were drawn to the salubrious peninsula buffered by mountains from the coldest Arctic blasts and an expanse of blue-green water from the hot, dry Sahara winds.We know that the Latin of the Romans, ancestor of Spanish, Italian and French, has a distant connection to the Indo-European languages of the Eurasian steppe. Languages as distinct as Hindi, Russian, and Italian all share a common ancestor. Genetics now tells us that the people who brought Latin to Italy arrived on the peninsula around 2400 BC. Meanwhile, archaeologists and historians have long known that 2,000 years ago, with the rise of Rome as a Mediterranean power, waves of Greeks arrived in the city. After his victory in the east, the general Aemilius Paulus brought 150,000 Greek slaves to Rome. 1,000 Greek nobles also arrived as hostages, including the historian Polybius. Ancient DNA now confirms that foreigners were indeed numerous during the Imperial period. But they left few descendants. The Rome of the Middle Ages was resettled by Italians from villages and farmsteads. There was a genealogical break with antiquity, if not, happily for us, a cultural one.Understanding Italy’s genetic history allows us to answer deeper questions about the cultural origins of Rome, and therefore the cultural origins of the West itself. Italy’s genetic story marries an undercurrent of depth and continuity to unceasing waves of change. The cosmopolitanism of the Imperial period was culturally and historically significant, leaving an indelible stamp upon later generations. But genetically, the impact was ephemeral as the Greek and Syrian people who populated the cities left little biological trace. Genetics bequeaths us a very different story than historical text and archaeological potshards.[snip]Though myths might tantalize, the truths uncovered by science can prove even more wondrous. Roman DNA samples from the Iron Age: the period of the Roman Kingdom and Roman Republic, ~1000 BC to 27 AD, still exhibit the same genetic patterns that emerged with the arrival of Indo-European peoples from the north during the early Bronze Age around 2400 BC. All the numerous tribes across the peninsula evident in the earliest Republican writings: Etruscans and Gauls in the north, Umbrians and Latins in the center, and Oscans in the south, have origins that date back to this period. The patchwork of tribes, clans and alliances emerged through the clash and synthesis between the descendants of the Neolithic Anatolian farmers and the Indo-European pastoralists. All of the people of ancient Italy were a synthesis of these two strands, both culturally and genetically.[snip]Genetic analysis of hundreds of remains of ancient Romans and Italians over thousands of years delivers us an answer to this paradox. Romans during the Imperial period, between 1 and 500 AD, do indeed show evidence of being genetically cosmopolitan, with ancestry from the Eastern Mediterranean. The waters of the Syrian Orantes did indeed merge with the Tiber, overwhelming it even. These were the people leaving inscriptions in Greek and Aramaic in Rome. There were the Emperors and their retinues from the provinces at the elite levels, and slaves and laborers among the populace.But something strange happens after the fall of Rome. After 500 AD, the genetics of the Romans resembles that of the Iron-Age Italians again, from before the Roman Empire. Novel signatures of Eastern Mediterranean ancestry disappear. How did this happen?[snip]Rome after the fall of the Empire was genetically a different Rome. It was replenished from the hills of Latium, now Lazio, just as the ancient city had been stocked with migrants from backwater hill tribes. The inability of the native Roman nobility to replace itself was an active concern for Emperor Augustus, who penalized childlessness and offered rewards for those having three or more offspring. Though the cities of the Empire were cosmopolitan, it seems likely that the rural areas remained as they always had been: populated by descendants of the Iron-Age. This is why the genetics of modern Italy show evidence of extremely ancient differences between the various provinces: these localities have likely been continually inhabited by the descendants of the old Italian tribes. Culturally, the Samnites, Sabines, and Oscans, may no longer exist, but genetically they long outlived the sophisticated citizens of the capital whose language they adopted and identity they co-opted.[snip]The genetic character of both Europe and Italy has changed multiple times since the end of the last Ice Age. Ancient DNA and modern genomics both tell us that. But, most of the variation we see today dates to the Iron Age and late Bronze Age. Italians are a genetic cluster that emerged between 4,000 and 3,000 years ago. These were the tribes and nations that are recorded in the first histories of the Greeks. These Iron-Age tribes carried a mix of two ancestries. The early farmers who set out from Anatolia, crops and domesticated animals in tow, still contribute the largest proportion of modern Italian ancestry. These people did not speak Indo-European languages, and the Etruscans were their cultural heirs.But the language spoken in Italy today descends from that of the Indo-Europeans, who contribute the rest of the heritage of most Italians. Indo-Europeans transformed Italy culturally, reshaping it to the bone. The name “Italy” itself means “land of young cattle” in the extinct Oscan language, a nod to the pastoralist proclivities of the Indo-Europeans. The gods and customs of the Romans were a complex synthesis of indigenous and Indo-European. The latter connections tie them together with people to their north, as well as groups as far afield as India.But if the genes of prehistory shaped the population of modern Italy, it is the memes of the Imperial period that leave an even stronger imprint. Genetics shows that modern Italians are differentiated from region to region correlated with ancient tribal boundaries, but all speak languages descended from Latin, the dialect of a set of tribes in Iron-Age coastal central Italy.The collapse of the Empire also triggered a demographic collapse. The cosmopolitanism of the late Empire disappeared, as the Italy of towns gave way to the Italy of villages. When Rome and the other cities of the peninsula began to recover in the late medieval period, their growth was driven by the migration of rural Italians whose ancestors had never ventured to Imperial Rome. These people were genetically similar to their Iron-Age predecessors so that the citizens of Rome, Naples and Florence resembled those of Republican Rome, and not the Empire, in terms of their deep heritage. But the Renaissance led to a second flourishing of ideas and forms that date to the Imperial period. The culture that the Medici recovered and patronized owed its character to texts retrieved from the Imperial period, and architecture that persisted down from antiquity. Florence’s Duomo looks back to the Roman Pantheon, not the hilltop fortifications that the ancestors of the Florentines occupied after the barbarian invasions. The people of the Empire may not have left physical descendants, but their cultural heirs remain today, carrying on their legacy.[snip]Given the nature of ancient cities, it is not entirely surprising in hindsight that the genetic impact of cosmopolitan urban areas proved evanescent. Though the Syrians and Greeks may loom large in the writings of the great thinkers of the ancient world due to their exoticism and large numbers, it was the fact that these people wrote things down that mattered more. The genes of all ancient city-dwellers, Roman, Greek or Syrian, likely do not benefit us today. It is the impact of their thoughts, their ideas, their culture that we live with, that nourishes us. The modern Roman is the biological descendent of a humble villager from 2,000 years ago, but blessed with a cultural patrimony shaped by the poetry of Virgil, the Gospels of the Bible, and the grandeur of the Roman Forum. Modern Italy is the spiritual child of ancient Rome, but the genetic descendent of its own bucolic hinterlands. As for the ancients, ye shall know them by their works, for that is all they left.
Read the whole thing for links and a lot more material and nuance.
I am broadly in agreement with Khan's interpretation and the distinction between the apparent genetic heterogeneity of imperial cities versus the reality of the countryside is an important insight.
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